Hansa Biopharma AB (publ)

Good day and welcome to the Hands of Biopharma year end and fourth quarter 2024 report. All participants will be in listen only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on a touch tone phone. To withdraw your question, please press star and then two. Please note this event is being recorded. I would now like to turn the conference over to Soren Tolstrup, President and CEO. Please go ahead.

Thank you, operator. Good afternoon, good morning, and welcome to the Hensa Biopharma conference call to review the full year and Q4 results for 2024. I'm Soren Tolstrup, President and CEO of Hensa Biopharma. Joining me today is Evan Ballantyne, Chief Financial Officer, and Hito Kaufmann, Chief R&D Officer. Please turn to slide two. Please allow me to draw your attention to the fact that we'll be making forward-looking statements during this presentation, and you should therefore apply appropriate caution. Please turn to slide three and then overview today's agenda. Today, we'll discuss the progress we made during the fourth quarter and review the full year of 2024 performance. The presentation should take roughly 15 to 20 minutes, after which there will be an opportunity to ask questions during a Q&A session. Please turn to slide four and an overview of our Q4 and full-year performance. Let's first begin with full-year performance. Total revenue for 2024 was 220.9 million SEC, and full-year IDFRIC sales totaled 189.7 million SEC, representing an 83% increase over the prior year. This performance excludes the impact of a provision of 49.6 million tech taken in 2024 to reflect discounts and a one-time retroactive rebate linked to successful special early access programs since the launch of ID3 in 2020. Including the impact of the provision, full year 2024, total revenue was 171.3 million tech, representing a 28% increase versus prior year. Additionally, full-year ID4X sales, including the impact of the provision, total 140.1 million tech, representing a 35% increase over the prior year. The solid year-over-year ID4X sales growth reflects continued strong launch execution in Europe, which has resulted in an increase in clinical utilization in key markets and continued advancement of regional and local clinical guidelines on the appropriate use of ID4X in highly sensitized kidney transplant patients. We're especially encouraged not just by the growing number of key clinics with specific itabrix protocols in place, but also the growing number of clinics with repeat itabrix usage following successful outcomes of first transplants, and we see this as a key driver of expected future growth. Please turn to slide five. I'd also like to highlight the trailing 12-month product sales data that shows performance over the previous year. This underscores the continued launch progress and growing market uptake without quarterly volatility due to variations in the flow of organ offers to specific highly sensitized patients waiting for an organ offer. Volatility we expect will continue, albeit with diminishing effect over time as we expand the ongoing usage of IDFRIX and penetrate new markets throughout Europe and beyond. Please turn to slide six. 2024 saw much progress in our pipeline projects, and we're very pleased with the delivery of several key pipeline catalysts and advancement of scientific exchange. Of note, we announced positive results from our Phase II trial in GBS and results of an indirect treatment comparison to the International Guillain-Barré Syndrome Outcome Study, or IGUS, demonstrating the potential of imifidase, our first-generation IgG-cleaning molecule, to address a significant unmet need in GBS. Additionally, we completed enrollment in our Phase 3 study in anti-GBM and initiated a Phase 2 trial with our partner, Jonathan, in Crickler-Najjar syndrome. This marked our second gene therapy trial to commence last year. The first trial was a Phase 1B study with our partner, Sarepta, in Duchenne muscular dystrophy. This trial continues to enroll patients. 2024 also marked significant progress with HANSA 5487, our next-generation IgG-cleaning enzyme with redosing potential. In October, we share positive data from our 12-month analysis of the NICE-01 first-in-human study. This analysis demonstrated that HANTSA-5487 can robustly and rapidly reduce ITG levels, has redosing potential, and a favorable safety and tolerability profile. Early in the year, we completed randomization of all patients in the U.S.-confided phase 3 trial in kidney transplantation. The trial is on track for data readout in the second half of 2025, followed by the expected submission of a BLA to the US FDA under the accelerated approval pathway. Lisa will share more details in a few minutes about these trials and our clinical development plans. Before moving to the next slide, I'd like to highlight our successful efforts to communicate the benefits of amlifidase in scientific publications and presentations at leading medical congresses around the world. Please turn to slide seven for an overview of the commercialization of itabrix in Europe. We continue to make solid commercial progress with Idafrix in Europe as a desensitization treatment and kidney transplantation. Due to the continued successful launch efforts in the number of centers gaining clinical experience with Idafrix continues to grow with three additional centers added in Q4 and more than half of all clinics utilizing Idafrix more than once after a positive first clinical experience. Additionally, I'm pleased to share that following the team's successful engagement with key opinion leaders in Europe and medical societies there, there are now two published international consensus documents providing guidance on desensitization in kidney transplantation. The most recent guidance was published in Transplant International, providing specific guidelines on the appropriate use of amlifidase in clinical practice to enable kidney transplants in highly sensitized patients. Finally, Thanks to our continued successful market access efforts, we recently secured reimbursement in three additional European markets. Hansa now has secured reimbursement in 18 markets, including the five largest European markets. We recognize the innate volatility in organ transplantation market due to variations in the flow of organ offers, but are encouraged by the growing number of clinics that are ready to treat with Idafrix and the increase in new and repeat users. providing a solid foundation for expected continued growth and market uptake. I will now turn it over to Hisu for an update on the pipeline and clinical development. Please turn to slide eight.

Thank you, Theron. Please turn to slide nine for an update on the pipeline and clinical development highlights to date. As you can see, we continue to make good progress across the pipeline in all three therapeutic areas, And in the fourth quarter, we shared several updates in both the autoimmune and gene therapy areas. I'll now walk through some of the specific trials and studies we have ongoing and the clinical development plans we have in place. Please move to slide 10. Let me start with the left-hand side of the slide and reiterate the continuous focus of Hamza on advancing science in areas where there remains high unmet medical need. I'm pleased to share But over the course of 2024, we have presented at several leading congresses in autoimmune, gene therapy, and transplantation, and published 10 articles in peer-reviewed journals. These efforts underscore our commitment to advancing the understanding of potential applications for our molecules, as well as the science behind complex conditions with very few treatment options. On the right-hand of the slide, you can see a summary of the progress we have made in 2024, and specifically the clinical development of inlifidase in 15487. In autoimmune, we communicated two key pieces of data in Q4. The first is the positive results of the 15H meditis O9 phase 2 study of inlifidase, an indirect treatment analysis of that data to the International Guillain-Barré Syndrome Outcome Study, or IGOS, in Guillain-Barré Syndrome, also known as GBS. The second is the completed enrollment of GUDIDIS-02 Phase III trial in anti-GBM. The GUDIDIS-02 trial is a Phase III open-label controlled randomized multicenter trial across Europe and the U.S. and is evaluating renal function and the need for dialysis at six months in patients with severe anti-GBM disease. Anti-GBM is a rare severe autoimmune condition affecting around 1.6 people per million annually. Encouraged by our Phase II data, we believe imlifidase has significant potential in improving the outcome of these patients and address the unmet medical needs. Imlifidase has been granted often drug designation for the treatment of anti-GBM disease, by both the U.S. Food and Drug Administration and the European Medicines Agency. Q4 also marks the commencement of our second trial in gene therapy. In December, we announced the initiation of a trial with Genton, one of our gene therapy partners, in Priglin-Major syndrome. The trial, GNT-O18-IDIS, is a Phase II trial in patients with Krasnoyarsk syndrome with pre-existing antibodies against adeno-associated virus vectors, or AAV. The trial will evaluate the efficacy and safety of single intravenous administration of Geniton's gene therapy, GNT-0003, following pretreatment with imbifidase. Antibodies against ACE vectors remain a major challenge, as their presence in patients excludes them from entering clinical studies with potential curative gene therapy treatments and from access to currently marketed and future gene therapies. Kriglin-Major syndrome is a rare genetic liver disease characterized by abnormally high levels of bilirubin in the blood, which leads to irreversible neurological damage manifested as muscle weakness, lethargy, deafness, intellectual disability, and eye movement paralysis. At present, patients must undergo phototherapy for up to 12 hours a day to keep the bilirubin levels below the toxicity threshold. Kregler-Majard syndrome is an ulcerative disease affecting less than one case per one million per year. GNT3003 is currently being evaluated in a pivotal clinical study in France, Italy, and the Netherlands and has received prime status from the European Medicines Agency. Of note, enrollment in SRP 9001-104 Phase 1B trial continues. As a reminder, the trial is evaluating the use of amlifidase as a pretreatment to Siretia Therapeutics' elevated gene therapy in Duchenne muscle dystrophy. In transplantation, we continue to progress enrollment of patients in the Post-Authorization Efficacy and Safety Study, PAES, as part of our obligation to the European Medicines Agency. As mentioned, we are now at 96% enrollment rate, with 48 out of 50 patients enrolled. This study will support the adoption of Idiferix more broadly and allow even more clinics to gain clinical experience. Once completed, centers are expected to commence or increased usage of commercial product. And the confided U.S. pivotal trial 3 in phase 3 was fully randomized in May, and we plan to deliver data in the second half of 2025, followed by a VLA submission to the U.S. FDA. Moving to 154.87, our next-generation IgG-cleaning enzyme, in October of 2024, we announced positive results of the 901st in human trial and findings from a 12-month analysis of that data. The analysis demonstrated that HANSA 5487 can robustly and very rapidly reduce IgG levels, has redosing potential, and a favorable safety and tolerability profile. We believe HANSA 5487 has a highly differentiated profile compared to published data from studies with other IgG-targeted therapies. AMSA 5487 has the potential to address significant unmet need across a spectrum of chronic autoimmune diseases, where IgG plays a role in disease pathology, including autoimmune conditions, and where the need for management of repeat acute immune system attacks is crucial. We will focus initial clinical development in new autoimmune diseases with a well-characterized role of specific autoantibodies in disease pathology, and recurring acute phases, specifically myasthenia gravis, or MGE. A significant number of patients with chronic neurological autoimmune diseases face exacerbations and even severe crisis, leading to hospitalization, demonstrating the high unmet medical need today. In the first half of 2025, we plan to align with regulatory agencies on the clinical development part of HANSA 5487 in myasthenia gravis. Please turn to slide 11 for a summary of the data from 15H metitis study in GBS. I want to spend just a few minutes providing a bit more context on the 15H metitis 09 and the indirect treatment comparison to IGOS. As a reminder, 15H metitis 09 is an open-label, single-arm, multicenter study across the UK, France, and the Netherlands. Patients with severe GBS included all patients with a disability score at and above 3. The study evaluated safety, tolerability, and efficacy of single-dose amlifidase in combination with intravenous hemoglobin or IVIG in 27 adult GBS patients. Data from the study demonstrated that severe GBS patients treated with amlifidase plus IVIG had rapid overall improvement in functional status, including expedited recovery of muscle strength, rapid return to independently walking, and a median time to improve by at least one grade in the GBS study at six days. The key results from the study are one week after treatment, 37% of patients were able to independently walk, and the median improvement in muscle strength was 10.7 points, as assessed by Medical Research Council, or MRC, some score. Additionally, the median time to independently walk for patients treated in the study was 16 days. Finally, at week eight, 67% of patients were able to walk independently, 41% of patients had regained the ability to run, and 37% of patients had improved by at least three points in the GBS disability score. Finally, at six months, 63% of patients were able to run or had no functional disability. Please turn to slide 12. When compared to the IGOS Reward Comparative Group, 754 severe GBS patients treated with IVIG patients in the 15-meta-IDIS study, which included 27 severe GBS patients treated with imlicidase in combination with IVIG, experienced statistically significant improvements across several clinical meaningful measures. The indirect treatment comparison concluded that patients in the 15-H-meta-IDIS-09 study treated with imlicidase plus IVIG returned to independently walking six weeks sooner, when compared to severe GBS patients in the IGOS real-world comparator group treated with IVIG alone. Additionally, patients in the 15 HMED-ISO9 study experienced statistically significant improvement across several clinically meaningful measures at multiple time points. At week one, patients were 6.4 times more likely to walk independently compared to the IGOS real-world comparator group. In GBS, IgG is a key driver of inflammatory attacks on peripheral nerves and has been clinically linked to the severity and progression of the disease. Rapid reduction of IgG levels has the potential to benefit GBS patients by depleting pathological IgG antibodies, thereby halting disease progression, resulting in faster recovery and less severe disease. Improvement in GBS disability score is important because it directly affects the clinical outcomes, recovery, and quality of the life for patients. Better management of disease severity can help reduce the risk of life-threatening complications, shorten recovery time, prevent long-term disability, lower healthcare costs, and improve overall patient well-being. We believe these results demonstrate the significant role that illicit AIDS may play in the treatment of GBS in combination with the standard of care IVIG. Unlike other molecules, illicit AIDS can effectively and very rapidly cleave IgG, potentially halting the progression of nerve damage associated with GBS and stopping the progression of the disease. I will now turn it over to Evan to cover financial performance. Please turn to the slide.

Should we advance one more slide? Thank you, Hito. Let's walk through the company's financial performance for Q4 in the full year. Revenue for the full year totaled 171.3 million SECs. representing a 28% increase from the previous year of 134.1 million SEC. Q4 revenue totaled 32.3 million SEC, including a difference product sales of 25.6 million SEC. Excluding the impact of the aforementioned provision, product sales for the full year were 189.7 million SEC, representing an increase of 83% or 86 million sec compared to the prior year product sales of 103.7 million sec. It is important to recognize that despite strong full-year 2024 sales of Idifrex, quarterly sales continue to fluctuate as a direct result of variations in the European kidney allocation systems. As mentioned in previous quarters, the company recorded a provision totaling 49.6 million SEC to reflect discounts and a one-time retroactive rebate on cumulative sales since the launch of Adiferex in 2020. At this time, the company does not expect any further provisions will be necessary. Next slide, please. Oops, 15. SG&A expenses totaled approximately 88.5 million SEC for Q4 and 343.8 million SEC for the full year 2024. Full year SG&A expense was 106.7 million SEC, or 24% favorable compared to the prior year. Restructuring activities helped reduce total year-over-year SG&A expense. And as previously mentioned, SG&A expenses included a restructuring reserve of approximately 3.5 million SEC. For the full year 2024, SG&A expense included a 24 million SEC non-cash charge related to the company's long-term incentive programs, or LTIP. R&D expenses totaled approximately 101.4 million SEC for Q4 and approximately 375.7 million SEC for the full year. Full year R&D expense was 36 million SEC or 9% favorable compared to the prior year. The favorable decrease in R&D expense was primarily driven by restructuring actions. The full-year R&D expense included approximately 7.9 million SEC of non-cash charges related to the company's LTIP program and a restructuring reserve of 6.6 million SEC. For the full-year net financial income and expense, resulted in total expense of approximately 166.3 million SEC compared to 42.3 million SEC in Q3 or in 2024 or 2023. In Q4, net financial income and expense represented an expense of approximately 100 million SEC in contrast to income of 51.3 million SEC in Q4 of 2023. Changes in financial income and expense are primarily driven by non-cash expense related to the NovaQuest note and changes in the U.S. dollar exchange rate against the Swedish krona. The full-year operating loss of 641.4 million SEC was 147.3 million SEC, or 19% favorable compared to the operating loss of 788.5 million SEC in 2023. The Q4 operating loss of approximately 173.6 million SEC was essentially flat compared to the prior year. The improvement in Hans' operating loss compared to the prior year was driven by increased sales as well as an overall reduction in expense. Please turn to the next slide. Cash used in operations for Q4 totaled 148 million SEC and 675 million SEC for the full year ended December 31st. As previously mentioned, the company completed the direct share issue of approximately 372 million SEC or approximately 35 million U.S. dollars in the second quarter. In Q4, cash and cash equivalents totaled 405 million SEC. I'd like to turn the presentation back to Soren. Please turn to slide 17.

Thank you, Evan. With this overview, our presentation is now concluded, and we would like to open the call for questions. Operator, please begin.

We will begin the question-and-answer session. To ask a question, you may press star then 1 on your touch-tone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you'd like to withdraw your question, please press star and then two. Our first question comes from Suzanne van Hodecien with Kempen.

Please go ahead. Hi, team. This is Suzanne from Kempen. Thanks for taking my question. Could you elaborate a bit more on your planned regulatory interactions on the repeat dose candidates in MG, like what type of meeting is it that you plan with the FDA, and what should we expect in terms of an update on next steps for this program in the first half of this year? And in a similar fashion, you've had the phase two comparison data for GBS. What are next steps for this program, or when should we hear more on advancing the program into a phase three? And then I have a follow-up as well.

Well, thank you, Suzanne, for those two questions. So first on the planned interaction with regulatory agencies on the next step for 5487. As we have communicated, it is our intent to move into Mycena Gravis here. And so the plan for this interaction is to consult and get feedback on the proposed clinical trial design. And we said earlier during this call, we expect this interaction to happen in in the coming months, essentially. I don't know, Jesus, do you want to add anything to this?

Sure. Thank you, sir. And just to add a little bit of flavor here, very specifically, we are planning for a phase 1B study in patients. And we have, as you can imagine, detailed the protocol and we'll discuss it. We'll have authorities, especially since in Myasthenia gravis, it's important to carefully consider the population of patients that you want to target in an early study. You could also safely assume that there will be some dose finding elements in there. However, we will only post-conversation with health authorities detail out the study plan. And that's what you can expect at some point in time.

Got it.

Thanks, Jesus.

And for GBS?

Yeah, and for GBS. Again, Jesus, do you want to take this?

Sure. So our refined thinking on GBS is clear to commence with a Phase III study that would have a control arm that reflects the current either standard of care or practice of medicine, depending on which country you look at, which is essentially IVIG. So that's what we've disclosed so far. And again, we're in continuous dialogue there as well.

Got it. Thank you. Maybe with regards to the Phase II readouts for the U.S. kidney trial and the study in anti-GBM in particular, what amount of data disclosure can we expect in a top-line release? Will this be primarily qualitative in nature of meeting the endpoints or not, or will you also report the kidney function result itself and perhaps some more? Thank you.

Well, thanks for that additional question, Suzanne. we expect that, you know, the first readout essentially would be the overall conclusion right on primary endpoint. And I think these two trials have been very carefully designed to be able to make a conclusion on that. And then, of course, subsequently there will be more full disclosure of additional results.

All right. Thank you.

Thanks, Hassan. And the next question comes from Alexander Kramer with ABG. Please go ahead.

Yes, good afternoon. I have two questions. Maybe to start with looking at the outlook into 2025, what are the key triggers that could drive and improve the EU sales? Is it a finalization of the PEAS study? Is it the neurotransplant or is there some other component which I'm missing here? And then I have a second question.

Well, thanks, Alexander, for that question. So we're quite optimistic for 2025. We've seen solid growth in 2024. If we look at all of the indicators of a successful launch, you know, i.e. number of clinics with protocols in place, number of clinics that have tried the product, number of clinics that have tried the product successfully and have used it in a second and third patient and so on. All of the lights there are on green. We are also expanding the footprint, the reimbursement footprint in Europe. Towards the end of the year, we got reimbursement at the national level in Spain and Italy, two very important kidney transplant markets in Europe. It's being translated from the national level to the regional level in Italy. I think we're at north of 90% of regions. And in Spain, we now have reimbursement in the second very important region. We got the first, Catalonia, very recently. That's the most important region in Spain. And so we are seeing large opportunities becoming available for sales this year. So that's certainly one part of it. impacting our thinking around the growth opportunities in 2025. Another is, as you mentioned, the completion of enrollment in the post-approval efficacy study. We're very, very close to having this fully involved. 48 out of 50 patients have been involved. Obviously, these patients have kind of been cannibalizing sales in the past, and when the study is fully involved, we expect that these key vendors that now have significant experience actually transplanting patients using IDF-RACE to desensitize ahead of the transplant will be converted to commercial sales. And they have even lined up patients as part of participating in this trial. So that's clearly also going to be a growth driver in 2025. And then you mentioned the year transplant program, which covers Germany, Benelux, Croatia, Hungary, Slovenia. a few other countries, and that is moving forward as well. So as that progresses and data becomes available throughout the participating clinics and they gain experience, we expect a positive impact also on transplants taking place outside of this specific program. So there's really a number of reasons why we think 2025 is going to be another year with significant growth.

Okay, thank you. And a second question on the Sarepta. Maybe it's a mistake, but in the report, I think you do not write anymore the initial data readout in 2025, but I think you had it on the slides. Could you elaborate a little bit, like, what are the bottlenecks with that trial? I mean, I know Sarepta is running it, but maybe you could shed a little bit more light on on what this means in terms of like also the milestone payments and the collaboration revenue you expect from Sarepta into 2025. This is something that is going to increase compared to 24 levels.

So as you said, this study is being run by a partner, Sarepta. We have a very good collaboration with them, and we are excited to see the trial progress. It's still enrolling patients. and so patients are being lined up and enrolled, and we do expect data to be available this year. This is what Sarepta has also communicated, you know, in the public domain. So, as I said, moving forward as planned, and we're really excited about that. We're also very excited about the second clinical stage trial we have ongoing in the gene therapy space with our French partner, Genathon, in Cricklin-Ajar, where we have started the trial and we have involved the first patient. This is a group of patients where there's a very high proportion of them that have too high titers of neutralizing antibodies against the vector used in the gene therapy, and therefore there's a significant unmet medical need and a very serious disease to enable administration of hopefully successful gene therapy in these patients. moving forward as well, and we're certainly hoping to get data this year as well in that disease. And that will be then in different tissue than the Sarepta trial in Duchenne. In Duchenne, it's muscle tissue. In Krigana-Jar, it's liver tissue. So 25, we hope, is going to be a very, very exciting and important year for our efforts in the gene therapy space.

Great. And maybe just on the financial aspect of the Sarepta, please.

Yeah, well, there's a number of milestones, as you know, significant amount of milestones potentially ahead, right up to just shy of $400 million. We have not communicated the specifics around, you know, timing and so on of these milestones. But obviously, as the program progresses, this is becoming more near term.

Okay. All right. Great. Thank you very much.

Thanks, Alexander.

And the next question comes from Douglas Zhao with HC Wainwright. Please go ahead.

Hi. Can you hear me? Yes. Good morning, Doug. Hey, good morning, Soren. Maybe just to start with the performance in the fourth quarter, was there any particular markets that maybe were sort of came in below sort of your current expectations? I know there's always some variability, but Just were there any sort of specific markets in particular, I'm thinking about France, that may have been a little slower than had been the prior trend?

I cannot offer that level of granularity. What I do want to say overall is, as we've discussed, and as you know very well, Doc, you know, sales is volatile, right? Whether a number of patients are transplanted this side of the quarter or the other side really depends on availability of of organs and acceptance of organs and the value of one single transplant versus the total sales is significant and material, right? So I'm not surprised that we see, you know, a quarter that is not on a par with the previous quarter, which was our best quarter ever, right? So that's what I can say. I would say on France, that France really continues to be a growth driver. We're very, very encouraged by what we've seen in France. And again, France is the one major market in Europe where we've had access for a number of years through the Early Access Program. And it is a country where there was a little bit of experience early on that we've been able to leverage and spread throughout the country. So we're looking really to emulate what has happened in France and some of the other key markets. And certainly a promising one is Spain, which is really one of the most sophisticated markets in the transplant markets in Europe. So we're encouraged by what we've seen so far. I should mention that we're also, you know, looking at some markets outside of Europe, like Australia, where we got approval with a label even including living donor situations. That's obviously a way to expand the market and be less exposed to the challenge of competing for available deceased donor organs. And so hopefully, you know, we're negotiating with the Australian authorities. But that's a market where also right now there is actually material significant experience. I think it's around eight patients that have been transplanted and quite a number of those living donor transplants. So we have good hopes there. And clearly ahead of us are the very important markets, not just, you know, in Europe, Middle East, Asia, Latin America, but also importantly the U.S., of course.

And maybe as a follow-up question in terms of GBS, there has been some other clinical development activity by competitors. I'm just curious, does that influence in any way how you're thinking about sort of moving into a pivotal study design? Thank you.

Yes, you're right. There has been recent clinical activities in that space. And actually, we've been encouraged by the attention that this has attracted to Clearly there is a high medical need for these patients. It's a very serious disease. It just hits you very, very suddenly. These patients are hospitalized in ICUs, and it's extremely important to have very fast, very rapid and significant impact on the disease. And so we're very encouraged by the data that we've been able to generate, looking at also patients in the ICUS database, And that kind of confirms our intent to, you know, move forward in this market. We have not changed our plans for, let's say, the sign of phase three trial or anything based on newly available data from other trials. We think, you know, this is a great way to demonstrate a benefit versus standard of care, which really in the U.S. and in Europe is IVIG. So we think we have a really, really good starting point to generate the data that the market will value and will guide their prescription pattern.

Okay, great. Thank you so much.

Thanks, Doug. And the next question comes from Eric Young with William Blair. Please go ahead.

Hi, this is Eric Young for Matt Fitch. Thanks for taking the question. Just two questions. So first, after the seasonality impact in the fourth quarter, can you comment on all about how the transplant rates have started in the 2025 year? And secondly, can you characterize and provide any additional granularity on how much benefit completing the post-authorization efficacy study will provide to revenue in Europe in 2025?

Thanks, Eric, for those two questions. So as far as seasonality is concerned, I think it's too early to say that there's specific seasonality here. Like I explained, we have expected from the start that there would be significant volatility quarter on quarter, just depending on the organ offer flow and whether specific organs are accepted by specific clinics for specific patients. And I'm not going to comment on how this year has started and and so on, other than saying that, you know, clearly we expect, for the reasons that I discussed just before, we expect continued, you know, strong growth in Europe. Then you asked about the benefits, specific benefit of the post-approval efficacy study. And really, of course, there are two benefits, well, three, I should say. First, as I discussed earlier, the fact that all patients soon will be enrolled means that there will be no cannibalization going forward. We're talking about 50 patients that have been transplanted in this trial in parallel with us actually marketing commercial products in the same region. So that effect is going to stop. Then you will have centers that will be ready to use commercial products and who will have actual experience and even protocols in place in these clinics. So that's going to be helpful as well. And then of course, um, we are looking forward, of course, to getting the data. Um, we believe that the data, uh, will, uh, reinforce, um, uh, the, the, um, let's say the, the positive position of, of it breaks in the market. Uh, we have generated now, quite some data also commercially transplanted patients or data has been generated in various markets. And that has been reflected also in guidelines and so on. We believe that additional data obviously will be helpful. And of course, in the end, we're looking to get full approval in Europe based on the totality of data generated also from this post-approval study.

Got it.

Thank you. Thanks, Eric. And the next question comes from Joanne Amaram with Red Eye. Please go ahead.

Thank you for taking a question. Yes. First, moving into then 2025, what about the ability to see patients that are about quality pipeline of patients, patients being ready at centers, what's your level of visibility as you move into 2025?

Yeah, great question. So what we've seen over the past, you know, 12 to 18 months is actually an increase in the pipeline of patients, right? They're being identified. They're being identified by the centers and and by specific programs like the Your Transplant program, which screens a large number of patients and then identify quite a number and so on. So there's a growing pipeline of patients, and that, again, confirms the unmet medical need and also the desire by the clinics and the medical community to actually do something. Clearly, what you also want to see at some point is that patients start to become active, right, because there is a competition for available deceased donor organs. But typically, again, through my experience with previous launches, that is going to come at some point. There is increasing awareness of the fact that some patients really don't have access to life-saving kidney transplants, and I don't think that that's going to be accepted for many years into the future. So we're also looking for patient calls at some point.

Thanks. That's very useful. And related to that, of course, that you're not in a position or nobody is to promote off-label use, but perhaps there is a sense or if you notice that there are centers keeping very strict to the label or is it or some considering using your products also for less extremely sensitized patients?

Well, I mean, let's say the The rules, the guidelines, instructions for what patients qualify and what patients don't qualify vary from country to country and sometimes from center to center. But in general, of course, it's unlabeled in the sense that they're transplanting highly sensitized patients that are unlikely to be transplanted given local organ allocation systems. So that's the overall judgment that's being used by the centers and other decision makers here.

Interesting. And finally, then, on the Pius Studio study, is it possible to give a sense of how many new centers that has not been that are naive to ID3 earlier that it will sort of be added towards the network with the study. And also the same question for the neurotransplant program.

Well, I mean, of course, from the start, all of the senders have been more or less naive, right? We have a limited number of centers involved in phase two trials. And therefore, the confidants trial is important, not just in generating data, but also in generating experience in what are really the key centers for kidney transplantation in the U.S. And as you know, we have involved a large number, you know, 20 centers here. And so the situation in the U.S. is going to be very, very unlike the situation in Europe in that we're going to have at least 10 times as many, you know, key clinics would experience at the time of launch. And we've seen in France what that means, right? So we've essentially done the most perfect pre-marketing job you can do, namely run this phase three trial against the U.S. kidney allocation system. So the centers have also learned how to operate within that system. So we're really encouraged by the progress there, the engagement by the trial sites, And also broadly in the U.S., we've been in contact, of course, with HRSA and other key, you know, stakeholders and decision makers in this space. The current administration is also very, let's say, I wouldn't say optimistic, but they're really pushing for an improvement in the transplant rate whenever possible. last in in power they they set a target of stopping the transplant rate in in the u.s and i've heard numbers as high as you know north of 60 000 transplants now there are 20 something thousand so that's that's really good tailwind as as well and so we think that there are a lot of indicators um showing that the u.s opportunity is very very material and that we're able to we'll be able to um explore uh explore and exploit that um much faster than what has happened in europe

Excellent. That's very useful. I think about Europe and the neurotransplant program. That program is also adding centers, presumably, and also the confirmatory study in Europe.

Yes, absolutely. So, again, the neurotransplant study is obviously a regulated, planned way of generating experience in these particular patients in Europe and participating countries. And so that's also great. And then the post-approval efficacy study clearly involves centers also that from the start didn't have experience, and now they have experience and even protocols in place, as I said. So that's important. I mean, say a country like the Netherlands, for instance, which has a number of centers participating, it's going to be very important for that country that, you know, now the study is fully involved soon and, of course, with hopefully supporting data.

Excellent. Is it possible to ask questions regarding OPEX and especially R&D?

Yeah, you can have one last question, Johan. Thank you.

Yeah, R&D side, it was a step up in Q4. What sort of level of trending should we expect moving into 25? Is Q4 a level we should be familiar with, or is this a bit on the high side?

I'll turn it over to Evan here. I think it's a bit on the high side right now, but look, the CONFIDAS trial in the U.S. is winding down. As he had discussed, he's meeting with the FDA and regulatory bodies in Europe and the U.S. to launch trials, additional trials for 5487. So my expectation is that in the latter half of the year, we'll see R&D expense go up. as we enter those clinical trials, but come down as we complete the PAES trial, which, as Soren mentioned, is almost fully enrolled, and as we complete the CONFIS U.S. Phase III trial.

So it sounds like we should expect a bit lower in the first half and then perhaps trending upwards afterwards. Yep. Excellent. Thank you.

This concludes our question and answer session. I would like to turn the conference back over to Soren Tolstrup for any closing remarks.

Well, thank you, Aubrey, and thank you, everyone who called in. We appreciate your interest in HANSA. We've got an exciting year ahead of us and look forward to keeping you updated. Thank you.

The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.