Hansa Biopharma AB (publ) (HNSA) Earnings Call Transcript & Summary

Good day, and welcome to the Hansa Biopharma Year-End and Fourth Quarter 2024 Report. [Operator Instructions] Please note this event is being recorded. I would now like to turn the conference over to Soren Tulstrup, President and CEO. Please go ahead.

Thank you, operator. Good afternoon, good morning, and welcome to the Hansa Biopharma conference call to review the full year and Q4 results for 2024. I'm Soren Tulstrup, President and CEO of Hansa Biopharma. Joining me today is: Evan Ballantyne, Chief Financial Officer; and Hitto Kaufmann, Chief R&D Officer. Please turn to Slide 2. 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 3, and an overview of today's agenda. Today, we'll discuss the progress we made during the fourth quarter and review the full year 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. Now please turn to Slide 4 and an overview of our Q4 and full year performance. Let's first begin with full year performance. Total revenue for 2024 was SEK 220.9 million, and full year Idefirix sales totaled SEK 189.7 million, representing an 83% increase over the prior year. This performance excludes the impact of a provision of SEK 49.6 million taken in 2024 to reflect discounts and a onetime retroactive rebate linked to successful special early access programs since the launch of Idefirix in 2020. Including the impact of the provision, full year 2024 total revenue was SEK 171.3 million, representing a 28% increase versus prior year. Additionally, full year Idefirix sales, including the impact of the provision, totaled SEK 140.1 million, representing a 35% increase over the prior year. The solid year-over-year Idefirix 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 Idefirix in highly-sensitized kidney transplant patients. We're especially encouraged not just by the growing number of key clinics with specific Idefirix protocols in place, but also the growing number of clinics with repeat Idefirix usage following successful outcomes of first transplants, and we see this as a key driver of expected future growth. Please turn to Slide 5. 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. The volatility we expect will continue, albeit with a diminishing effect over time as we expand the ongoing usage of Idefirix and penetrate new markets throughout Europe and beyond. Please turn to Slide 6. 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-Barre Syndrome Outcome Study or IGOS, demonstrating the potential of imlifidase, our first-generation IgG-cleaving molecule to address a significant unmet need in GBS. Additionally, we completed enrollment in our Phase III study in anti-GBM and initiated a Phase II trial with our partner, Genethon in Crigler-Najjar Syndrome. This marked our second gene therapy trial to commence last year. The first trial was a Phase Ib study with our partner, Sarepta in Duchenne Muscular Dystrophy. This trial continues to enroll patients. 2024 also marked significant progress with HNSA-5487, our next-generation IgG-cleaving enzyme with redosing potential. In October, we shared positive data from our 12-month analysis of the NICE-01 first-in-human study. This analysis demonstrated that HNSA-5487 can robustly and rapidly reduce IgG 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. ConfIdeS Phase III 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 U.S. FDA under the accelerated approval pathway. Hitto 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 imlifidase in scientific publications and presentations at leading medical congresses around the world. Please turn to Slide 7 for an overview of the commercialization of Idefirix in Europe. We continue to make solid commercial progress with Idefirix in Europe as a desensitization treatment in kidney transplantation. Due to the continued successful launch efforts in the number of centers gaining clinical experience with Idefirix continues to grow with 3 additional centers added in Q4 and more than half of all clinics utilizing Idefirix 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 2 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 imlifidase 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 3 additional European markets. Hansa now has secured reimbursement in 18 markets, including the 5 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 Idefirix 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 Hitto for an update on the pipeline and clinical development. Please turn to Slide 8.

Thank you, Soren. Please turn to Slide 9 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 3 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 continued focus of Hansa on advancing science in areas where there remains high unmet medical need. I'm pleased to share that 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 imlifidase and HNSA-5487. In Autoimmune, we communicated 2 key pieces of data in Q4. The first is the positive result of the 15-HMedIdeS-09 Phase II study of imlifidase and indirect treatment analysis of that data to the International Guillain-Barre Syndrome Outcome Study or IGOS in Guillain-Barre Syndrome, also known as GBS. The second is the completed enrollment of GOOD-IDES-02 Phase III trial in anti-GBM. The GOOD-IDES-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 6 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 improving the outcome of these patients and address the unmet medical need. Imlifidase has been granted orphan 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 Genethon, one of our gene therapy partners in Crigler-Najjar Syndrome. The trial, GNT-018-IDES is a Phase II trial in patients with Crigler-Najjar 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 Genethon's gene therapy, GNT-0003 following pretreatment with imlifidase. Antibodies against AAV 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. Crigler-Najjar 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. Crigler-Najjar Syndrome is an ultra-rare disease affecting less than 1 case per 1 million per year. GNT-3003 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 Ib trial continued. As a reminder, the trial is evaluating the use of imlifidase as a pretreatment to Sarepta Therapeutics ELEVIDYS gene therapy in Duchenne Muscular 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 Idefirix more broadly and allow even more clinics to gain clinical experience. Once completed, centers are expected to commence or increase usage of commercial product. And the ConfIdeS U.S. pivotal trial in Phase III was fully randomized in May, and we plan to deliver data in the second half of 2025, followed by a BLA submission to the U.S. FDA. Moving to HNSA-5487, our next-generation IgG-cleaving enzyme. In October of 2024, we announced positive results of the NICE-01 first-in-human trial and findings from a 12-month analysis of that data. The analysis demonstrated that HNSA-5487 can robustly and very rapidly reduce IgG levels, has redosing potential and a favorable safety and tolerability profile. We believe HNSA-5487 has a highly differentiated profile compared to published data from studies with other IgG-targeted therapies. HNSA-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 neuro autoimmune diseases with a well-characterized role of specific autoantibodies in disease pathology and recurring acute phases, specifically myasthenia gravis or MG. 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 path of HNSA-5487 in myasthenia gravis. Please turn to Slide 11 for a summary of the data from 15-HMedIdeS study in GBS. I want to spend just a few minutes providing a bit more context on the Phase II of 15-HMedIdeS-09 and the indirect treatment comparison to IGOS. As a reminder, 15-HMedIdeS-09 is an open-label, single-arm multicenter study across the U.K., 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 imlifidase in combination with intravenous immunoglobulin or IVIg in 27 adult GBS patients. Data from the study demonstrated that severe GBS patients treated with imlifidase 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 1 grade in the GBS study at 6 days. The key results from the study are 1 week after treatment, 37% of patients were able to independently walk and the mean improvement in muscle strength was 10.7 points as assessed by Medical Research Council or MRC sum score. Additionally, the median time to independently walk for patients treated in the study was 16 days. Finally, at week 8, 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 3 points in the GBS disability score. Finally, at 6 months, 63% of patients were able to run or had no functional disability. Please turn to Slide 12. When compared to the IGOS real-world comparative group, 754 severe GBS patients treated with IVIg patients in the 15-HMedIdeS study, which included 27 severe GBS patients treated with imlifidase in combination with IVIg experienced statistically significant improvements across several clinical meaningful measures. The indirect treatment comparison concluded that patients in the 15-HMedIdeS-09 study treated with imlifidase plus IVIg returned to independently walking 6 weeks sooner when compared to severe GBS patients in the IGOS real-world comparator group treated with IVIg alone. Additionally, patients in the 15-HMedIdeS-09 study experienced statistically significant improvement across several clinically meaningful measures at multiple time points. At week 1, patients were 6.4x 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 nerve 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 health care costs and improve overall patient well-being. We believe these results demonstrate the significant role that imlifidase may play in the treatment of GBS in combination with the standard of care IVIg. Unlike other molecules, imlifidase 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 [ Slide 13. ]

Could we advance one more slide? Thank you, Hitto. Let's walk through the company's financial performance for Q4 and the full year. Revenue for the full year totaled SEK 171.3 million, representing a 28% increase from the previous year of SEK 134.1 million. Q4 revenue totaled SEK 32.3 million, including Idefirix product sales of SEK 25.6 million. Excluding the impact of the aforementioned provision, product sales for the full year were SEK 189.7 million, representing an increase of 83% or SEK 86 million compared to the prior year -- compared to the prior year product sales of SEK 103.7 million. It is important to recognize that despite strong full year 2024 sales of Idefirix, 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 SEK 49.6 million to reflect discounts and a onetime retroactive rebate on cumulative sales since the launch of Idefirix in 2020. At this time, the company does not expect any further provisions will be necessary. Next slide, please, hope it is 15. SG&A expenses totaled approximately SEK 88.5 million for Q4 and SEK 343.8 million for the full year 2024. Full year SG&A expense was SEK 106.7 million 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 SEK 3.5 million. For the full year 2024, SG&A expense included a SEK 24 million noncash charge related to the company's long-term incentive programs or LTIP. R&D expenses totaled approximately SEK 101.4 million for Q4 and approximately SEK 375.7 million for the full year. Full year R&D expense was SEK 36 million or 9% favorable compared to the prior year. The favorable decrease in R&D expense was primarily driven by restructuring actions. Full year R&D expense included approximately SEK 7.9 million of noncash charges related to the company's LTIP program and a restructuring reserve of SEK 6.6 million. For the full year, net financial income and expense resulted in total expense of approximately SEK 166.3 million compared to SEK 42.3 million in Q3 in 2024 -- 2023. In Q4, net financial income and expense represented an expense of approximately SEK 100 million in contrast to income of SEK 51.3 million in Q4 of 2023. Changes in financial income and expense are primarily driven by noncash 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 SEK 641.4 million was SEK 147.3 million or 19% favorable compared to the operating loss of SEK 788.5 million in 2023. The Q4 operating loss of approximately SEK 173.6 million was essentially flat compared to the prior year. The improvement in Hansa's 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 SEK 148 million and SEK 675 million for the full year-ended December 31 -- December 31. As previously mentioned, the company completed a direct share issue of approximately SEK 372 million or approximately USD 35 million in the second quarter. In Q4, cash and cash equivalents totaled SEK 405 million. I'd like to turn the presentation back to Soren. Please turn to Slide 17.

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

[Operator Instructions] Our first question comes from Suzanne van Voorthuizen with Kempen.

This is Suzanne from Kempen. Could you elaborate a bit more on your planned regulatory interactions on the repeat dose candidate 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 II comparison data for GBS. What are next steps for this program? Or when should we hear more on advancing the program into a Phase III? And then I have a follow-up as well.

Well thank you, Suzanne, for those 2 questions. So first, on the planned interaction with the regulatory agencies on the next step for 5487. As we have communicated, it is our intent to move into myasthenia gravis here. And so the plan for this interaction is to consult and get feedback on the proposed clinical trial design. And we -- as said earlier during this call, we expect this interaction to happen in the coming months, essentially. I don't know, Hitto, do you want to add anything to this?

Sure. Thank you, Soren. Just to add a little bit of flavor here. Very specifically, we are planning for a Phase Ib study in patients -- and we have, as you can imagine, detailed the protocol, and we'll discuss that with health authorities, especially since in myasthenia gravis, it's important to carefully consider the subpopulation of patients that we 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. And for GBS?

Yes. And for GBS, again, Hitto, do you want to take those?

Sure. So our refined thinking on GBS is clearly 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 are in continuous dialogue there as well.

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

Well, thanks for that additional question, Suzanne. So we expect that the first readout essentially would be the overall conclusion right on primary endpoint. And I think these 2 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.

And the next question comes from Alexander Kramer with ABG.

I have 2 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 further finalization of the PEAS -- PEES study? (sic) [ PAES study ] Is it the Eurotransplant -- or is there also some other component, which I'm missing here? And then I have a second question.

Well, thanks, Alexander, for that question. So we are quite optimistic for 2025. We've seen solid growth in 2024. If we look at all of the indicators of a successful launch, i.e., number of clinics with protocols in place, a number of clinics that have tried the product, a number of clinics that have tried the product successfully and have used it in the 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, 2 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 Catalunya 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 enrolled. 48 out of 50 patients have been enrolled. Obviously, these patients have kind of been cannibalizing sales in the past. And when the study is fully enrolled, we expect that these key centers that now have significant experience actually transplanting patients using Idefirix 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 Eurotransplant 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. And 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 what this means in terms of like also the milestone payments and the collaboration revenue you expect from Sarepta into 2025. Is this something that is going to increase compared to '24 levels?

So as you said, the study is being run by our 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 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, Genethon in Crigler-Najjar, where we have started the trial and we have enrolled 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 in a very serious disease to enable administration of hopefully successful gene therapy in these patients. So 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 Crigler-Najjar, 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?

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

And the next question comes from Douglas Tsao with H.C. Wainwright.

Can you hear me?

Yes.

Just -- 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, Doug, 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 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, that we see 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, right? 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 kidney transplant markets in Europe. So we're encouraged by what we've seen so far. I should mention that we are also 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, 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 8 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 other very important markets, not just 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?

Yes, you're right. There has been recent clinical activity in that space. And actually, we've been encouraged by the attention that this has attracted. Clearly, there is a high unmet 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 are very encouraged by the data that we've been able to generate looking at also patients in the IGOS database, and that kind of confirms our intent to move forward in this market. We have not changed our plans for, let's say, design of a Phase III trial or anything based on newly available data from other trials. We think 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.

And the next question comes from Eric Yeung with William Blair.

This is Eric on for Matt Phipps. Just 2 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 or 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 2 questions. So as far as seasonality is concerned, I think it's too early to say that there is specific seasonality here. Like I explained, we have expected from the start that there will 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 so on other than saying that clearly, we expect for the reasons that I discussed just before, we expect continued strong growth in Europe. Then you asked about the benefits -- specific benefit of the post-approval efficacy study. And really, of course, there are 2 benefits; well 3, 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, right? We are 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 product 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, we are looking forward, of course, to getting the data. We believe that the data will reinforce the -- let's say, the positive position of Idefirix in the market. We have generated now quite some data also on 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.

And the next question comes from Johan Amaram with Redeye.

Johan Unnerus. Yes. First, moving into then 2025, what about the ability to see patients that are about calling pipeline of patients, patients being ready at centers, what's your level of visibility as you move into 2025?

Yes, great question. So what we've seen over the past 12 to 18 months is actually an increase in the pipeline of patients, right? They're being identified. They are being identified by the centers and by specific programs like the Eurotransplant program, which screens a large number of patients and then identified quite a number and so on. So there is 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 pull at some point.

That's very useful. Then -- 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 -- are some considering using your products also for less extremely sensitized patients?

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

Interesting. And finally, then on the ConfIdeS studio -- study, is it possible to give a sense of how many new centers that has not been that are naive to [ IVIg ] earlier that it will sort of be added to the network with the prior study. And also the same question goes for the -- also the same question for the Eurotransplant program?

Well, I mean, of course, from the start, all of the centers have been more or less naive, right? We have a limited number of centers involved in our Phase II trials. And therefore, the ConfIdeS 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, north of 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 10x as many key clinics with experience at the time of launch. And we've seen in France what that means, right? So we've essentially done the most perfect premarketing job we can do, namely run this Phase III 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 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. When they were last in power, they set a target of doubling the transplant rate in the U.S. and I've heard numbers as high as north of 60,000 transplants. Now they're at 20-something thousand. So that's really good tailwind as well. So we think that there are a lot of indicators showing that the U.S. opportunity is very, very material and that we're able to -- we'll be able to explore and exploit that much faster than what has happened in Europe.

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

Yes. Yes, absolutely. So again, the Eurotransplant study is obviously a, let's say, regulated, planned way of generating experience in these particular patients in Europe in 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, take 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 now the study is fully enrolled soon and of course, with hopefully supporting data.

Excellent. Is it possible to ask a question regarding OpEx and especially R&D?

Yes, you're going to have one last question Johan, where you choose.

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

I'll turn it over to.

Yes, Evan here. I think it's a bit on the high side right now. But look, we -- the ConfIdeS trial in the U.S. is winding down. As Hitto 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 ConfIdeS 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?

Yes.

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

Well, thank you, operator, 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 has now concluded. Thank you for attending today's presentation. You may now disconnect.