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

Hello, everyone, and welcome to the Hansa Biopharma Year-end Report for January through December 2021. [Operator Instructions] Today, I am pleased to present CEO, Søren Tulstrup. Speakers, please begin.

Thank you, operator. Good afternoon, Good morning, and welcome to the Hansa Biopharma conference call reporting the year-end results for 2021. I'm Søren Tulstrup, CEO of Hansa Biopharma. With me today, I have our CFO, Donato Spota; as well as our Head of Investor Relations, Klaus Sindahl. Today, we'll review the overall progress and highlights of our business in the most recent quarter and provide a preview of our near-term milestones. Our presentation should take approximately 20 minutes, and after that we'll take your questions. Now please turn to Slide 2. Please allow me to draw your attention to the fact that I'll be making forward-looking statements during this presentation, and you should therefore apply appropriate caution. Please turn to Slide 3. 2021 was overall a transformative and successful year for Hansa Biopharma. It was a year in which we advanced into a fully integrated commercial stage biopharmaceutical company following the commercial launch in Europe of Idefirix label for desensitization of highly sensitive kidney transplant patients and compatible to disease donor. From a strategic point of view, we experienced strong execution throughout 2021 on our key priorities, including meeting our R&D, commercial and organizational objectives for the year. In addition, I'm very encouraged by the high level of interest from other health care companies to engage with Hansa. During the last 12 months we've entered into 3 new collaborations, providing further external validation of the potential of our unique antibody-cleaving enzyme technology platform. On the operational side, we've seen solid execution and expanding our market access and geographical footprint in Europe. Pricing and reimbursement have been secured in 4 countries now, including Sweden and the Netherlands as well as on an individual hospital basis in Finland and Greece. Market access procedures are currently ongoing in 14 countries following the submission in January this year of HTA dossier in Spain. With this, we have now completed submission of HTA dossiers in each of the 5 largest markets in Europe. This is a great achievement by our market access team, establishing an important foundation for Hansa's commercial rollout of Idefirix and helping to bring hope to the thousands of highly sensitized patients across the continent who are currently waiting for a compatible kidney transplant. Looking beyond the early launch countries, I was also pleased that we could announce a multiregional commercialization partnership in December of last year with Medison Pharma for Idefirix in Central Eastern Europe and Israel. Medison is a highly recognized global pharma company focused on providing access to innovative therapies in international markets. And this commercial partnership represents the first milestone for Hansa as we continue to expand access to Idefirix beyond core markets. In the U.S., we announced that the first patients in our pivotal ConfideS trial in kidney transplantation were enrolled at the Columbia University Medical Center in New York. The ConfideS study is evaluating imlifidase as a potential to desensitization therapy to enable kidney transplants in highly sensitized patients waiting for a disease donor kidney through the U.S. kidney allocation system. We expect to enroll patients at 12 to 15 leading transplant centers across the U.S. with the aim of completing enrollment by the end of this year. The U.S. trial will generate both important data and valuable experience at these key centers. In gene therapy, we are pleased to announce an agreement with AskBio, a subsidiary of Bayer, to evaluate the feasibility of imlifidase as pretreatment ahead of gene therapy in Pompe disease in patients with [ too high titus ] of neutralizing antibodies against the AAV vector used. This new collaboration with AskBio marks another important step in the implementation of our partnership strategy in the gene therapy space, where neutralizing antibodies against the adeno-associated virus commonly used as a vector in gene therapies represent a major challenge and where we see significant potential for our antibody-cleaving enzyme technology to help overcome this barrier. Turning now to our ongoing Phase II programs for GBS and AMR. As of February 2, we have enrolled 23 out of the target of 30 patients in the AMR study, while 15 out of a target of 30 patients have been enrolled in the GBS study. In Anti-GBM, also known as Goodpasture disease, we recently announced plans to initiate a Phase III study of imlifidase following a successful pre-IND meeting with the U.S. FDA. The pivotal Phase III clinical study is expected to enroll approximately 50 patients across the U.S. and Europe with the first patient expected to be enrolled in 2022. As part of Hansa Biopharma's platform strategy and our efforts to broaden the application of imlifidase as a potential therapy to change the course of IgG-mediated immunological diseases, we are actively exploring new indications with a high unmet need. One such indication under consideration is allogeneic hematopoietic stem cell transplantation, also known as bone marrow transplantation. Desensitization treatment of patients with high levels of donor-specific antibodies prior to allogeneic stem cell transplantation is a challenge. And currently there are no approved drugs for managing these patients. We believe that imlifidase may have the potential to transform the standard of care in these patients by enabling clinicians to inactivate preexisting donor-specific antibodies prior to transplantation, thus enabling a successful transplantation. We'll get back to this exciting opportunity later in the presentation. Now please turn to Slide 4. As I said upfront, Hansa Biopharma's commercial launch activities are progressing as planned. Our goal is to have a positive impact on patients as we work closely with the transplant community to reshape the area of desensitization and integrate Idefirix into clinical practice as a new standard of care. Idefirix is the first and only approved drug to enable kidney transplants in highly sensitized patients in the EU who are incompatible with a disease donor and the long-term market uptake of innovative product is obviously dependent on successful early experiences in key early adopter clinics. As we discussed at the third quarter call last year, we measure our launch progress using a set of key commercialization metrics, which directly impact future adoption and sales of Idefirix as a new transformative therapy. One such metric is our ability to secure pricing and reimbursement at the right price and on label, which obviously will be of key importance for rollout of an uptake of Idefirix in the market. As indicated earlier, we are on track to secure access and funding market by market in Europe with reimbursement now secured in Sweden and the Netherlands as well as on an individual hospital basis in Finland and Greece. Additionally, we have ongoing market access procedures in 14 countries. During the fourth quarter, specifically, we initiated processes in France, Belgium and Greece. Moreover, a health technology assessment dossier for Spain was submitted last month, which completes HTA filings in each of the 5 largest markets in Europe. On the clinical side, we continue to work with a number of priority centers to ensure and optimize their clinical readiness as a number of incompatible patients are being identified and prioritized for kidney transplantations in the coming months. So far, 10 clinics are considered clinically ready to take on highly sensitized patients for incompatible kidney transplant, and we continue to work closely with additional centers across Europe on their preparedness through training, KOL engagement, protocol drafting and logistics. In relation to the awareness and interest metrics, we see extensive engagement with more than 30 experts committed to operationalizing HLA- incompatible kidney transplants for some of their highly-sensitized patients. As highlighted at our last conference call, one of the key outcomes from the European Society of Organ Transplantation Conference in Milan last summer was the formation of the new work stream, the leading transplantation KOLs to prepare clinical guidelines for incompatible kidney transplant patients. This new ESOT work stream is expected to be a key driver for harmonization of approaches across Europe to transplanting highly sensitized patients and ensuring positive outcomes for patients in transplant programs. As a potentially transformative innovative new drug, Idefirix is still considered experimental by many in the field, and the ESOT guidelines also serve to clearly articulate the need to transplant these patients who currently typically wait longer for a transplant, or in most cases never receive one. The first phase of the ESOT guidelines is aimed at providing an evidence review of the literature with clearly articulated recommendations and statements of the issues for incompatible kidney transplant patients. The second phase was focused on the use and patient outcomes [ assay experience within new today's growth ] within the transplant community. Now please turn to Slide 5. As highlighted in the beginning of the call, we recently announced a new multiregional commercialization partnership in the kidney transplantation with Medison Pharma covering Israel and major countries in the Central and Eastern European region such as Poland, Croatia, Hungary and Slovenia. This is an important milestone for Hansa as it helps expanding access to Idefirix for highly sensitized patients awaiting kidney transplants in markets beyond the early launch countries. The commercialization is based on the current conditional marketing authorization for Europe and pending marketing authorization by Israel's Ministry of Health. An application for marketing authorization for desensitization treatment in kidney transplant was filed in Israel in June of last year. If granted, Israel will be the first market outside of Europe where Idefirix is commercialized. Hansa and Medison will collaborate on obtaining pricing and reimbursement in the 5 countries that are scoped within the commercialization agreement. Now please turn to Slide 6. On January 3 this year we announced a collaboration agreement with AskBio, a subsidiary of Bayer AG, and a fully integrated AAV gene therapy company dedicated to developing medicines that improve the quality of life for patients with genetic diseases. The collaboration will evaluate the potential use of imlifidase as a pretreatment prior to the administration of AskBio's therapy in Pompe disease in a preclinical and clinical feasibility program for patients with preexisting neutralizing antibodies to adeno-associated viruses. Under the terms of the agreement, Hansa received a USD 5 million fee upon execution of the agreement. And AskBio has a right of first negotiation for full development and commercialization agreement following evaluation of the results from an initial Phase I/II study. This collaboration will AskBio marks another important step in the implementation of Hansa's partnership strategy in the gene therapy space where neutralizing antibodies against AAV vectors used in a broad range of investigational gene therapies remain a major challenge. Please turn to Slide 7. Part of Hansa Biopharma's platform strategy includes broadening the application of imlifidase as a potential therapy to change the course of IgG-mediated immunological diseases and conditions. Toward that end, the company is exploring new indications with a high unmet need. As noted earlier, one of the indications Hansa is currently exploring is allogeneic hematopoietic stem cell transplantation, also known as bone marrow transplantation. These stem cell transplantations are often acutely needed in a range of cancer patients with very low time to find an adequately matched donor. If we look at hematopoietic stem cell transplantation, we can distinguish between autologous and allogeneic transplantation. Autologous transplantations obviously don't represent issues as the bone marrow cells are transplanted from the patient's own body to replace the diseased bone marrow. In allogeneic stem cell transplantation, however, the situation can be different. In many cases, haploidentical donors are often available to patients, starting from parents, children or siblings, in which case the overall transplant outcome is generally good. However, the presence of donor-specific antibodies or DSAs can have a negative impact on transplant outcome and the prevalence of DSAs in allogeneic hematopoietic stem cell transplantation is typically between 10% and 21%. In particular, the presence of these antibodies can result in primary graft failure and is also linked to a significantly worse survival outcome for the patient. There are currently no approved drugs to manage patients with high levels of DSAs and current desensitization methods are considered inadequate, thus preventing patients from having a potentially life-saving procedure. We believe imlifidase may have the potential to transform the standard of care by enabling conditions to inactive DSAs prior to transplantation and we therefore decided that this is a priority indication for Hansa to further explore. Please turn to Slide 8. Turning now to our 2 ongoing clinical programs in active antibody-mediated rejection, AMR, and Guillain-Barré syndrome, GBS. In the AMR Phase II program, 23 out of the target of 30 patients have now been enrolled and we are on track to complete enrollment in the first half of 2022, as previously guided. We also expect to announce the first data readout from the AMR Phase II study in the second half of this year as previously guided. In the GBS Phase II program, we have now enrolled 15 patients out of a target of 30 patients. In this trial, we see how the impact of the persistent COVID-19 pandemic and the recent emergence of the Omicron variant leading to an escalation in number of infections and introduction of new quarantine rules have affected the availability of staff across a number of our trial centers. Additionally, the pandemic has led to a shortage of IVIg, affecting the enrollment rate in the program at a subset of participating hospitals. In order to help mitigate these hurdles and increase the enrollment rate, Hansa has recently simplified the study protocol, and we're also actively supporting the hiring of additional staff at certain clinics as well as adding 2 sites for the recruitment of patients in the U.K. and the Netherlands. Given the difficulty of predicting the near-term impact of the Omicron surge and the effects of the recently implemented remedial action to increase enrollment rate, we will revisit our guidance for completion of enrollment in connection with the publication of our Q1 report in April. In anti-GBM disease, also known as Goodpasture disease, we recently announced plans to initiate a pivotal Phase III study for imlifidase, following a successful pre-IND meeting with the U.S. FDA. The planned study is expected to enroll 50 patients across approximately 25 centers in the U.S. and Europe with the first patients expected to be enrolled this year. In kidney transplantation, we have now enrolled the first patients in our pivotal U.S. trial known as the ConfideS trial. The first 2 patients were recently enrolled at the Columbia University Medical Center in New York, and we currently have 5 centers open for recruitment. The ConfideS study is evaluating imlifidase as a potential desensitization therapy to enable kidney transplants in highly sensitized patients waiting for a disease donor kidney through the U.S. kidney allocation system. The U.S. trial will target 64 highly sensitized patients with a cPRA score of 99.9% and above, representing the group of patients with the highest unmet medical need. We expect to enroll patients at 12 to 15 leading transplantation centers across the U.S. and aim to complete enrollment by the end of this year. This randomized controlled trial will generate both valuable data and important experience at some of the key transplant centers in the U.S. As previously communicated, we expect to complete enrollment in this ConfideS study in the second half of 2022 with a 12-month follow-up on eGFR completed by second half of 2023. Results from the trial are expected to support a BLA under the accelerated approval pathway in the first half of 2024. Now please turn to Slide 9 and a summary overview of our pipeline. As depicted on this slide, thanks to the continued progress over the past few years, we have developed a broad clinical pipeline in both transplantation and autoimmune diseases. In addition, we have exciting preclinical projects ongoing in cancer and antidrug antibodies as well as in the very promising field of gene therapy, where as discussed we now have 2 ongoing collaborations with Sarepta Therapeutics and AskBio. The aim in both collaborations is to assess imlifidase as a pretreatment ahead of gene therapy with Sarepta investigating this approach in Duchenne and Limb-girdle muscular dystrophy. And in the case of the AskBio collaboration, the focus is on an Pompe disease. The preclinical development with Sarepta is progressing according to plan, while the program with AskBio has just commenced. Upon successful completion of these preclinical programs, we expect imlifidase to move into clinical trials. Beyond the gene therapy space, Hansa is also engaged in a preclinical collaboration with argenx, which is moving forward according to plan. The focus of this collaboration is to assess the potential benefits of combining imlifidase with efgartigimod argenx's FcRn inhibitor. With this overview I now hand over the call to Donato, who will take us through a high-level review of the 2021 financials. Donato, please.

Thank you, sir. And please turn to Slide 10. As Søren outlined, we achieved solid execution throughout 2021 on our key priorities, including meeting important R&D, commercial and organizational objectives for the year. Revenue for the full year of 2021 grew to SEK 34 million, including SEK 15 million in product sales, while the remaining SEK 19 million mainly stem from revenue recognition from the upfront payment the company received under the Sarepta agreement. Please turn to Slide 11. We continued to invest in the Idefirix launch and our pipeline in accordance with our strategic operational and financial plans. For the full year of 2021, SG&A expenses amounted to SEK 328 million (sic) [ SEK 327 million ] compared to SEK 203 million for 2020. The increase in expenses is in line with our objective to grow Hansa as a fully integrated commercial-stage biopharmaceutical company, and as such reflects our expanding commercial footprint and increased activities, including investments in the territories, marketing, market access and supply chain activities related to the launch of Idefirix. Our investments in R&D amounted to SEK 231 million for the full year 2021, which was roughly on par with our R&D expenses for 2020. Investing in R&D and our pipeline activities across all of our 4 strategic pillars remains a key priority for Hansa as it supports the long-term value creation for the shareholders of the company. The net loss for the full year of 2021 was SEK 548 million compared to SEK 423 million (sic) SEK 421 million for 2020. The increase was primarily driven by the ramp-up of our commercial activities. Please turn to Slide 12. Cash flow from operating activities amounted to minus SEK 481 million for 2021, which compares to minus SEK 290 million for 2020. The increase compared to 2020 is driven by our growth on the commercial front and the nonrecurring USD 10 million Sarepta upfront payment received in July of 2020. As of December 31, 2021, Hansa's cash position, including short-term investments, amounted to SEK 889 million, corresponding to approximately USD 95 million. With our current cash position and projected burn rate, we expect Hansa to be financed into 2023, as previously guided. I'll now hand back to Søren to give the final remarks.

Thank you, Donato. Please turn to Slide 13. Hansa Biopharma's transformation into a fully integrated commercial stage biopharmaceutical company became a reality in 2021, and we continue to demonstrate solid progress in executing on our corporate strategy, including making significant headway in our efforts to build and advance a pipeline of valuable drug candidates for rare neurologic diseases. Looking at the milestones ahead, we expect to complete the enrollment in our Phase II program in AMR in the first half of this year with the first data readout in the second half of the year, as previously guided. This guidance assumes no further escalation of the COVID-19 pandemic. With regards to our GBS program, as we discussed, it is too early for us to evaluate the impact of recent measures taken to increase the enrollment rate as well as the near-term impact with the recent surge in Omicron infections across Europe. So we'll revisit our guidance for completion of enrollment when we announced our Q1 results in April. In anti-GBM, we expect to commence a new Phase III study with the first patient enrolled in 2022. As far as NiceR is concerned, our next-generation enzyme program for repeat dosing scenarios, we expect IND-enabling tox studies to be completed in 2022. Upon successful completion of these studies, we expect to advance the NiceR program into clinical studies. In our U.S. ConfideS trial in kidney transplant, we recently enrolled the first patients and expect to complete enrollment by the end of this year, subject to any potential impact by the COVID-19 pandemic. We look forward to keeping you updated on our progress in advancing our mission to bring life-saving and life-altering therapies to patients with serious rare diseases while generating long-term value for our shareholders and society at large. Please turn to Slide 14. With this, we are now ready to take your questions. So I hand over to you, operator. Please begin.

[Operator Instructions] Our first question comes from Christopher Uhde with SEB.

They are focused on the clinical program. So I guess my first question is, can you just detail the protocol change for addressing COVID that you mentioned? And then can you also tell us a little bit about the design of the anti-GBM trial. I mean when do you expect to decide on the clinical -- yes, the exact clinical strategy for the [ allo STT ] is my third question.

Yes. So first, as far as the detail of protocol changes, I don't think this is the time to go through the specific details. I mean it's generally around some logistics around what needs to be done specifically around the intake of a patient, something around weekdays. And so our team has been working with the clinics to make sure that the best possible conditions are there for the clinics to actually accept these patients. The main issue really is, as you can imagine, the fact that they're short on staff. The fact that initially we had most of our centers in just one country that was France, heavily impacted by measures taken, quarantining staff, et cetera. And we've also seen, as I outlined, issues around supply of IVIg. So we're doing what we can to make sure that the best possible conditions are in place for the centers to accept patients. And as I also detailed, we have expanded the number of centers and also expanded the geographical footprint. So we'll get back to where we stand and where -- when we expect this [ stone, decided to be following all this ]. It's just impossible at this point in time. But certainly we hope this will happen in the near term with the measures that we've taken. On the second question was the specific design of the anti-GBM. So we have aligned with the FDA on the design of the study. We are also of course consulting with EMA. We want this to be a global trial. And the overall scope we've discussed with the 50 patients. We expect approximately 25 centers. This will be a controlled trial, and it's not one that will lead to conditional approval, but potentially would be pivotal leading to a full approval. The third question was specifically around hematopoietic stem cell transplantation. This is a space that we -- as I indicated, I think is very interesting. Clearly in our dialogues with key opinion leaders and also the regulatory authorities, specifically primarily the U.S. FDA, we do see a clear unmet need in these cases. Initially we wanted to focus on the malignant cancer types where there's a -- of course, a very serious situation. This is a fairly rare kind of situation to occur. But obviously if you look at the broader space, stem cell transplantation has really seen significant progress and donor-specific antibodies do present a problem across a number of different diseases. So we're excited about the opportunity, and we're continuing our dialogue with the FDA and regulatory authorities and experts. It's too early for us to give a guideline around or guidance around when we would initiate a trial. But certainly we're looking into preparing a protocol and getting the necessary approvals, and we'll update you as soon as we can.

Our next question comes from Adam Karlsson with ABG.

First one on sort of expectations for 2022 as it relates to the sales in a number of treated patients. You've obviously not provided any precise guidance in the report. I was wondering whether you could give any sort of indication on either of these parameters, say as to a number of treated patients. I imagine, I mean, given the coordinated launch you're pursuing, presumably you have a fairly good idea where you might end up. Or if not, what are the factors, I guess, beyond timing of reimbursing decisions that could sort of materially sway [ tails in ] 2022.

Yes. So thanks for the question. And we've discussed this in the past also. Right now it would not be helpful for us to try to provide guidance around sales and patients. This is really the early days of launching this transformative therapy. There's a lot of moving parts. And so what we're focused on is really seeing whether we need to keep or whether we see progress according to the key commercialization metrics that I discussed earlier, specifically getting reimbursement at the right price and on label, seeing clinics getting clinically ready to treat these patients, having local protocols in place, having staff that has been trained, et cetera. We are obviously looking at publication of guidelines and so on. And as I said, we expect the ESOT guidelines to be published very soon, which will be quite helpful looking at the broader European space. We're also looking at interest and awareness and support from key opinion leaders, et cetera, and measuring that obviously and some very nice progress. So I've been involved in quite a number of launches of transformative new therapies. And I'm very encouraged by what I've seen so far. We're essentially checking all of these boxes. And of course, as soon as we have less volatility and more predictability, we will start providing guidance. But at this point in time it's just too early.

Got you. And I guess on that point of sort of early key commercialization metric, can you give any sort of commentary on the experience that early launch clinics have had so far with imlifidase anecdotally? And have any clinics started to treat more than one patient, a second patient or so?

So I will not now, and not during the coming calls specifically. I mean you can imagine we're talking about very few centers and very few patients, start commenting on the outcome of what has happened in specific clinics and so on. That will be completely inappropriate. What I can say is that, obviously we have very good data from our Phase II trials showing 100% success rate in enabling transplantation, very good graft survival outcomes. We have followed these patients for many years. We have good data all the way now through year 3, 4 and into year 5. And so all of this and what we're seeing in the market today, again, as I said, brings comfort to me that we are on track, that this is a product that over time will hopefully enable a broader range of patients to benefit from life-saving kidney transplant. And obviously we will see data be reported. I expect clinics to start talking about individual patient experiences in relevant scientific floor, et cetera. So that will come. But it's just not for me to comment on these specific individual experiences.

Our next question comes from Johan Unnerus with Redeye.

Yes, a few complementary questions. What about funding for patients? Could you elaborate a bit more details how that plays out? Presumably it's very important ahead of reimbursement and guidelines.

Yes. So funding for patients obviously happens at several levels, if you will. There's a national level. And in some cases, like in Sweden, it's a recommendation, and then it has to be pushed down through the regions and the hospitals and have to also negotiate getting a budget and so on and so forth. In other countries like the Netherlands, it's more of a national decision that is automatically reimbursed and it's essentially implemented. And then you have, in addition to this you have specific situations where hospitals can apply for individual patients to get individual patients reimbursed or get the hospital reimbursed for expenses associated with treating individual patients. This is what is the case in New Finland, for instance. In Greece you also have currently permission for a number of patients and funding in place for this. In addition to these kind of general decisions and individual hospital-based decisions, we are also looking at early access programs in countries like France where there recently have been changes, making this a possible route for us. And we look at similar types of programs in other key countries in Europe. So overall, I'm very happy with the progress. We hope to have decisions from the German authorities and the U.K. at some point during the first half of this year. As I said, we now have ongoing processes in all of the top 5 countries in Europe. So we are on track, and we see a solid progress.

It seems to be a rather pragmatic approach, the different countries, and what -- how often are these reviews? Presumably there will be plenty more patient feedback from leading [ center ] publication, as you alluded to earlier in the call and information and during conferences, it's something that could lead to revisions in the funding ahead of formal reimbursement?

And so again, this is normal. I mean you always have kind of authorities looking at data as a product is being launched. What we have gotten here, I mean you have a variety of kind of systems in individual countries. In certain countries you also negotiate volumes and all kinds of things that can impact downstream, uptake and so on. But so far, as I said, we have very solid support and we have positive conclusions. And importantly, we have positive conclusions on the HTA dossiers that we have submitted with the value proposition like in Sweden where it has been concluded that by the independent board reviewing the cost-effectiveness and cost benefit of new therapies that imlifidase at the price level in Sweden is not only cost-effective but it may even be a cost saver for the system, depending on various assumptions for dialysis cost and outcomes. And that is actually something you see very rarely for these orphan drugs. So we're very comfortable with the, again the value proposition that we have and the response and the ongoing interactions with payers across Europe.

Excellent. And on a different, completely different, Israel is in the partnership with Medison. Is Israel first in queue?

If it's first in queue? In what sense?

Yes. I mean this collaboration covers several countries, Central Eastern Europe and Israel, of course, which country has total -- most -- has perceived longest in this, where can we expect sales activities or treatment activity to start, is that Israel?

It's impossible to predict. In Israel we have this application with the Israeli Minister of Health. And obviously first we need to get local regulatory approval in Israel. In the Eastern European countries, we are leveraging the EU approval essentially. So that's more a question of getting pricing and reimbursement in place and so on. So it's too different as I can't predict specifically where you'll see uptake first. But this is important. I mean obviously this is just one agreement, right? But if you look at the wider geography of the globe, there are many countries with significant opportunities, high volumes of kidney transplants. And obviously the same issues with sensitized patients. So we do see this as a first step in rolling out Idefirix to other key regions and countries, and we're quite encouraged by the dialogues we're having.

Yes. And we can see that you expand what can be referred to as the platform approach in different collaborations. Can you say something about the prospects and pipeline both regarding gene therapy and other commercial collaborations to capture other regions apart from Central Europe and Israel?

Well, so 2 different things, right. So one partnering effort is around ensuring launch of Idefirix across the globe essentially. So that's one effort. And as I said, we've taken a good first step here with the medicine agreement covering Central Eastern European countries and Israel. Then obviously we also have other types of partnerships in the gene therapy space. We have announced now 2 collaborative agreements AskBio and Sarepta. And what we're focused on here is really generating data with a variety of AAV vectors and in a variety of specific indications. Obviously, over time, we do see -- it's our vision to see imlifidase and other enzymes being used quite broadly in this space. And our key priority is to make sure that data are generated now with, as I said, a variety of vectors and gene therapies and different indications. And so that's our key focus. We may see additional activity in the gene therapy space, helping furthering our agenda there. But right now we are quite happy with the setup we have and the collaboration and the progress made. Obviously in the autoimmune disease space, we have an ongoing research collaboration with argenx. That's also progressing very well. We're looking at the potential combination of efgartigimod and imlifidase. We think there is a good case for using this combination in a variety of settings. We're generating preclinical data. And once we have that data set, we will discuss the next steps with argenx. In the autoimmune disease space, obviously there's a high number of IgG-mediated diseases with unmet medical needs. And clearly we're looking at how we can best develop drug candidates on our own and potentially in partnership with others. In the oncology field, and I mentioned this earlier in the call, we're looking at hematopoietic stem cell transplantation, but we certainly also see a potential use in imlifidase as a way to essentially potentiate the efficacy of immuno-oncology therapies like rituximab. We hope to have poof of mechanism at some point during this year, and then we'll certainly look at what the best approach is. Overall, the oncology field, given the complexities and the costs associated with operating in that space is a partnering space for us. So clearly, we are evaluating at what time point and in what way we [ could achieve ] a partner in the oncology space.

With that, can I expect more activities and collaborations in the oncology space as well?

Certainly a possibility. It's a fourth leg for us. We certainly see quite some potential in this space. It's a very competitive area, and there are clearly some players out there where it may make sense to have conversations at some point. But that's not where we are at this point.

Our next question comes from Zoe Karamanoli with RBC Capital Markets.

I have 2 questions, if I may. The first one, you mentioned that imlifidase sales will be slow and lumpy on a quarter-to-quarter basis. But if we look for the full year 2022, in the presentation you mentioned that you have 10 priority centers ready to take on patients. So do you think it's realistic to assume that each of these centers will treat the minimum of 2 patients in 2022? And if not, I will be keen to understand how you think this and what are the challenges. And then I have a follow-up question.

Yes. So Zoe, thanks for the question, and I will not provide guidance on patient numbers. But you're right, we have 10 centers ready, clinically ready. They also need to be commercially ready, have specific not just reimbursement but funding in place, et cetera. And they need to of course identify the patients and then get the patients that need to have organs allocated to these specific patients. So there's a lot of moving parts, and it's just impossible for me to give you any specific indication of patient numbers. But clearly we expect this number, the 10 centers to increase over the year. We expect that -- clearly we know that quite a number of these centers have identified patients already. Then depending on organ availability, et cetera, we also expect them to have first patient and they will evaluate the outcome on that first patient first before initiating or during the second patient. How many patients that will all add up to, I just cannot and will not give you a guidance on this call, but I understand that you're making your calculations.

Okay. And just as a follow-up, do you have some targets as to how many centers you want to have active by the end of 2022? And will you have activated all your Tier 1 centers? And where is the biggest opportunity you see in Europe?

Yes. So as far as the target for centers is concerned, it is -- as I said, we have 10 now, and now we expect more than 20 centers to be clinically ready, certainly by the end of the year. We have good traction across a number of countries and with a number of different clinics. Where do we see the biggest opportunities? Well, obviously, the volume is in the larger countries, right? But some of them will take some time before you get full access. Again, if you look at a country like France, there is a significant opportunity, potentially you can unlock part of that already this year with early access program. Spain is a significant overall opportunity, very strong interest from players that again will necessitate us getting special access. Clearly the U.K. and Germany are next in line of the large countries for access. We have some very interesting and interested centers in both countries. So I would expect both of these countries to be proportionally significant opportunities for us. And then of course you have the early launch countries like the Netherlands. We have 7 clinics that are essentially collaborating now, some of whom are quite ready and very eager to initiate and move further. So I think there is opportunity in a variety of countries.

Our next question comes from Dominic Rose with Intron Health.

This is Dominic from Intron Health. I've got 2. Question one is on imlifidase in bone marrow transplant. It may be a little early to say, but what are your current timeline expectations on this? And is there any way you can sort of accelerate the program? I understand that there are a lot of different things you're doing and it may not be a top priority, but anything you can say about what you're thinking of around that would be helpful. Question 2 is simply how much of the AskBio upfront payments do you expect to book in 2022?

Thanks for those 2 questions. So first on bone marrow transplantation, where we are right now is that we have had dialogues with key experts in the field, primarily in the U.S., but also in Europe at advice meetings. We have consulted with the FDA. There's a number of things that needs further exploration before you can design kind of the optimal protocol. Clearly, as I said, we see significant potential overall in the stem cell transplantation space. Initially, we want to focus on certain very serious diseases. It's also a question of managing risk and making sure that you have the right protocol in place. And so this is what we are looking at right now. And I can't give you a specific time line other than hopefully we will be able to, during this year, align around a protocol. And then we'll certainly, as soon as we are there, we'll provide further guidance.

Second question, do you have on the…

Yes. And I'll hand over to you to, Donato. That was around the $5 million upfront.

Yes. It's actually a nice way of asking around the AskBio timelines. But maybe what I can say is that we expect to record more than 50% this year or at least 60% this year and then the rest we'll see.

Our next question comes from Douglas Tsao with H.C. Wainwright.

Congrats on the progress, Søren. Just maybe as a starting point, you have market access procedures ongoing in I think you said 14 countries. I'm just curious, within the 5 largest markets or the Big 5, how many do you think -- is it realistic to think that you might be able to launch or sort of roll out commercialization in any of those markets this year and how many?

Yes. So we certainly hope that we will have possible outcomes in the U.K. and Germany. The process is moving forward. And as I said, potentially we could have a decision here in the first half of this year, enabling a launch later this year. Then you have countries like France where we're certainly looking into the possibilities for utilizing the early access program in that country. Same we're doing in some other countries. But I think further reimbursement for both Italy, Spain and France will likely come at a later stage. But clearly you'll see significant progress hopefully this year, and we'll have ongoing dialogues. So as soon as we're ready to provide more guidance on that, we will do that.

And then just in terms of -- a couple of questions on the pipeline, in terms of the U.S. trial with imlifidase for kidney transplant, is -- are you counting -- I think you indicated there were 2 patients who've been enrolled in the study. Is that [ they made it ] transplanted or patients [ we’ve been ] identified, enrolled in the study and potentially awaiting transplantation in the near future?

Yes. So what we report is, when they're enrolled, meaning that we have patient consent and they've essentially been enrolled into the study. It doesn't mean that they have been transplanted. So this is what we'll do going forward as well.

And typically what's the time line in your experience from the other trials, is that sort of time between from when they enroll to actually -- they are actually transplanted?

Well, it's very difficult to give you specific guidance on that. Obviously an organ has to become available through the kidney allocation system, and then they are randomized, there's not a match. So I can't give you specific data there. What I can say is that we expect to have 4 enrolled by the end of the year and that we would have data by the end of 2023. And this guidance is based on all the interactions we've had with the clinics and other players in this field in the U.S.

Okay. And then just one quick question on the NiceR program. I know you indicated to complete GLP tox studies this year, going into presumably a Phase I study next year. Would you anticipate that to be a healthy volunteer study? Or just given the nature of the therapy, would you potentially go into patients for like a Phase IIb study?

It really depends on the specific indications. So I can't say at this point in time. So -- but obviously we need to generate certain data with a new molecule, but it really depends on the specific indication. We're looking at multiple indications at this point in time.

And do you know when you'll pick an indication…

Yes. So once we have the full data sets and we make the analysis, certainly that's when we'll take the specific indication. And there's a range of spaces and specific indications where this will -- might make a lot of sense.

For our next question we have a follow-up question from Adam Karlsson with ABG.

Just a question on the [ Genova Select ] announcement last quarter. I can appreciate you may be limited in terms of what you can say publicly so, but have there been any sort of formal legal developments or escalations of that situation? Anything that you can share on that front would be appreciated.

As you indicated yourself, I mean we'll not comment specifically on any one situation. What I can say is that obviously looking at the overall gene therapy space as well as the other spaces we're in, we're very comfortable with our IP position and all the agreements we have with various players. And we're also very comfortable with the know-how and products and the data and everything. So we have a strong position. And to the extent that action is necessary in other fronts, that obviously will happen. And to the extent that we will report, that is because it's relevant and necessary. So that's what I can tell you.

We have no further questions. I will now hand back to our speakers for a final remark.

Thank you very much, operator. And thank you, everyone, for your time this morning, this afternoon. Very much appreciate it. It's a very exciting time for Hansa Biopharma. And as I said, we look forward to keeping you updated on progress. And with this, once again, thank you for your time.