Ladies and gentlemen, welcome to the Hansa Biopharma Q1 2023 conference call. My name is Glenn, and I'll be the moderator for today's call. If you'd like to ask a question during the presentation, you may do so by pressing star one on your telephone keypad. I will now hand you over to your host, Søren Tulstrup, CEO of Hansa Biopharma, to begin. Please go ahead.
Thank you, moderator. Good afternoon, good morning, and welcome to the Hansa Biopharma conference call to review first quarter 2023 results. I'm Søren Tulstrup, CEO of Hansa Biopharma. Joining me today is our CFO, Donato Spota, and Hansa's Head of Investor Relations, Klaus Sindahl. Today, we'll discuss the progress we made during the first quarter of 2023 and review our near-term milestones. The presentation should take roughly 15 minutes, after which there will be an opportunity to ask questions during a Q&A session. Now, 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 an overview of Q1 highlights.
In the first quarter of 2023, we continued to advance several key priorities, including progress for the European launch of Idefirix and our exciting pipeline. First, during this quarter, we were pleased to receive a positive reimbursement decision in Spain. Spain, one of the largest markets in Europe for kidney transplantation, with more than 3,400 kidney transplants carried out in 2022 alone. This is important news, especially for the thousands of patients in Spain who are still disadvantaged and in urgent need of more personalized and innovative desensitization options like Idefirix that can enable incompatible kidney transplantation. Our goal in kidney transplantation is to change the approach to desensitization and organ allocation by integrating Idefirix into clinical practice as a new standard of care for highly sensitized patients.
With this novel therapy, we're truly changing the transplantation ecosystem and advancing a treatment regimen from one that has been solely focused on compatibility to one that can accommodate transplants for incompatible patients who previously had no other choice of waiting and hoping. I'm happy to share that we have now seen the first repeat business of Idefirix at clinics in Europe. Securing repeated sales at the clinic level is a testament to our highly focused launch strategy, and we anticipate additional repeat orders as clinicians build valuable experience from treating and monitoring their first patients over several months. I'm also pleased to announce that we've expanded our commercialization partnership with Medison Pharma for Idefirix and kidney transplantation to cover the Baltic region.
As you may recall, in December 2021, Medison Pharma announced the formation of a multi-regional partnership to accelerate the commercialization of Idefirix into new markets through Medison's commercial platform. The initial agreement covered Israel and select Eastern European countries. The partnership has resulted in market access being secured in Poland and more recently in the Czech Republic, while marketing authorization in Israel was obtained in 2022. Now, if we turn to the pipeline, we're pleased with the recent advancements in GBS and with the lead molecule HNSA-5487 from our important second-generation enzyme program. In GBS, we announced completion of enrollment at the end of March, and we are also excited to have recently initiated a new clinical phase 1 trial in healthy volunteers with HNSA-5487. With regard to our US ConfIdeS study in kidney transplant, enrollment continues to progress as expected.
We continue to see strong interest from clinics to participate in this trial. We will add more centers, up to a total of 20, to accelerate randomization. On the organizational side, we welcome Matthew Shaulis as our new Chief Commercial Officer and President of our US affiliate. Matt joins Hansa from Pfizer, where he has held several senior executive roles, including President Inflammation and Immunology for the International Developed Markets, President North America Oncology, and most recently, Senior Vice President responsible for the company's global commercial and medical go-to-market model transformation. With more than 20 years of international experience in the pharmaceutical industry, Matt will further strengthen our commercial and in-market leadership team and create a US-focused organization that will help deliver our goal of bringing imlifidase to the US market. Please turn to slide four.
As mentioned in the beginning of the call, during the first quarter, we announced that Idefirix received a positive reimbursement decision in Spain. This is a key market. In fact, Spain has the highest rate of organ donation from deceased donors in the whole of Europe at approximately 90%, while one in five on the kidney wait list are classified as highly sensitized. With Spain secure, market access has now been secured in five of the largest markets in Europe in the last 12 months. This represents approximately 15,000 annual kidney transplants. In total, we now have access in 12 European markets with ongoing efforts in an additional eight countries, including Portugal, Belgium, and Switzerland. Please turn to slide five and a review of our ongoing clinical programs. At the end of March, we announced completion of enrollment in our GBS Phase II program.
GBS is an acute autoimmune attack on the peripheral nervous system, which affects approximately one to two patients per 100,000 annually. Top-line data on safety, tolerability, and potentially the early effect in imlifidase-treated GBS patients is expected to be announced in the second half of this year. The full data from the GBS Phase II study is expected in 2024 following a comparative efficacy analysis between the imlifidase-treated group of patients in the trial and a matched cohort from the IGOS database at the Erasmus Medical Center in Rotterdam. In anti-GBM, a pivotal phase III study began with a target of treating 50 patients with either imlifidase and standard of care or standard of care alone at 30 to 40 sites in the US and Europe.
The first site was initiated at the end of last year and will continue to add centers aiming at enrolling the first patients before summer as previously guided. With regard to our pivotal US ConfIdeS trial in kidney transplantation, 62 out of 64 patients have been enrolled. We continue to see strong interest from US clinics to participate in this trial, and we have taken a decision to increase the number of study centers from 13 to up to 20 to accelerate randomization. Increasing the number of centers will also help build valuable clinical experience in desensitization of highly sensitized patients among KOLs in preparation for our planned launch in the US market. Completion of study enrollment is expected shortly while randomization should be completed by the second half of 2023 as previously guided.
Lastly, we plan to publish the full data set for the AMR study in the second half of this year as previously announced following the positive top-line data announced in November of last year. Please turn to slide six. We're very excited about the potential use of our enzymes in the gene therapy space, both to enable use of AAV-based gene therapy in a broader range of patients and potentially to increase durability of response, reduce the AAV vector dose, and enable redosing of the gene therapy. Back in 2020, a paper published in Nature Medicine demonstrated the capacity of imlifidase to remove AAV antibodies and enable efficient transduction of the transgene in vivo in non-human primates and mice.
We've since been working to demonstrate similar results in an in vivo study where mice with severe combined immunodeficiency were pre-immunized with human IgG and then treated with imlifidase before gene therapy using AAV8. In the imlifidase-treated mice, transduction to all target organs was significantly improved compared to the group that was not treated with imlifidase. These results further highlight the ability of imlifidase to remove anti-AAV antibodies and support the rationale to use imlifidase as a pretreatment to enable gene therapy in that class of patients. In line with this, and as previously discussed, our partner Sarepta has announced their decision based on results from our collaborative preclinical efforts within their Duchenne muscular dystrophy program to take imlifidase into the clinic as a potential pretreatment ahead of their SRP-9001 gene therapy candidate.
On this note, the preclinical data with imlifidase will be presented by Sarepta at the American Society of Gene & Cell Therapy annual meeting, which takes place in Los Angeles next month. Please now turn to slide seven and a summary overview of our pipeline. As you can see on this slide, we've successfully developed a broad and exciting clinical pipeline in both transplantation and autoimmune diseases. In line with previous guidance, we have now advanced HNSA-5487, the lead molecule from our second-generation program, into the clinic following the approval of our clinical trial application end of last year. HNSA-5487 will be targeted towards relapsing immunologic disease where patients may benefit from more than one dose of an IgG-modulating enzyme. It may also have significant potential in the gene therapy space and within oncology.
Readout from the phase I program will help determine which potential indication area we will initially pursue with our second-generation enzymes. With this overview, I will now hand over the call to Donato, who will walk us through a review of the first quarter financials. Donato.
Thank you, Søren. Please turn to slide 8. Total revenue for the first quarter of 2023 amounted to SEK 24 million, including SEK 14 million in product sales and SEK 10 million in contract revenue, mainly from the agreement with Sarepta. While in Q1 we saw the volatility in quarter-on-quarter sales as discussed at earlier earnings calls, we are also starting to see repeat business at the first clinics, which we anticipate to increase throughout the year. At the same time, we do foresee sales benefiting going forward from new guidelines recently published by the British Transplantation Society for the UK, the ongoing revisions to the Eurotransplant allocation system, as well as new countries such as Czech Republic, Italy, and Spain, where we more recently secured market access.
In summary, we continue to expect a significant step-up in sales in 2023 compared to the last year, while quarter-on-quarter volatility may remain. Please turn to slide nine. Total SG&A expenses for the first quarter of 2023 amounted to SEK 103 million compared to SEK 80 million for the first quarter of 2022. The increase reflects Hansa's broadened commercial activities and organizational expansion related to the launch of Idefirix in Europe, but is also partly driven by inflation and devaluation of the Swedish krona against the euro and the US dollar. Q1 SG&A expenses include certain non-recurring one-off costs.
For the full year 2023, as previously guided, we do expect an increase in SG&A expenses over last year from initiatives to drive sales growth in Europe, as well as from starting to strengthen our US presence in support of late-stage development activities and preparation for potential US market entry. The inflation and foreign exchange rates are also expected to impact costs for the year.
R&D expenses amounted to SEK 93 million for the first quarter 2023, which is on par with the recent quarters and reflects an increase of SEK 22 million compared to the first quarter of last year. The increase over the same period last year is mainly driven by expanded pipeline activities, such as the ongoing US ConfIdeS study, the initiation of the anti-GBM phase III study, as well as the initiation of the clinical phase I trial and CMC development activities for HNSA-5487, our lead molecule from the second generation enzyme program. R&D costs are also impacted by price adjustments due to inflation and devaluation of the Swedish krona. As discussed at the last earnings call, starting with Q4 2022, we capitalized development costs related to the EMA post-approval commitments as we meet the respective accounting criteria on the IAS 38.
Capitalized development costs for Q1 2023 amount to approximately SEK 23 million. Looking at full year 2023, and as previously guided, we expect to increase our R&D investments over 2022 levels as we progress our pipeline. More specifically, the clinical and CMC development of HNSA-5487, our ongoing Phase III program in anti-GBM, the US ConfIdeS trial and post-approval study in Europe, as well as initiating the DSA rebound study in kidney transplantation. Net loss from operations amounted to SEK 182 million for the first quarter 2023, which was up from SEK 135 million in the same period of last year. Please turn to slide 10.
Cash flow from operating activities amounted to minus SEK 207 million for Q1 2023, compared to minus SEK 130 million for Q1 a year ago. The increase is mainly driven by the increase in operating expenses and the positive cash flow effect of the $5 million upfront payment related to our agreement with AskBio received earlier last year. Inflation and FX changes do also impact. In comparing the Q1 cash flow to Q4 2022, the difference is to a large extent driven by seasonality with regard to incoming and outgoing payments, for example, related to accounts receivable, accounts payable and accrued expenses, which helped the Q4 cash flow and burdened Q1 cash flow.
Our cash position at the end of March was approximately SEK 1.3 billion, which is expected to provide runway into 2025 as previously guided. I will now hand the call back to Søren for his final remarks.
Thank you, Donato. Please turn to slide 11 and an overview of near-term milestones. We're encouraged by the advancements being made across our platform and therapeutic areas. Looking ahead, there are several milestones we must deliver in 2023 and the years to come. As highlighted earlier, we continue to see strong interest among clinics to participate in our US ConfIdeS trial, and we'll continue enrollment to accelerate randomization by adding further centers up to a total of 20. Randomization is expected to complete in the second half of this year, as previously guided. In our pivotal global Phase III study in anti-GBM disease, we initiated the first site at the end of last year, and we're currently working to add sites. As previously guided, we expect the first patient to be enrolled before summer.
Additionally, following promising preclinical data with imlifidase in their Duchenne muscular dystrophy program, our partner Sarepta has announced plans to advance imlifidase into the clinic this year as a potential pretreatment in DMD patients with pre-existing IgG antibodies to Sarepta's gene therapy SRP-9001. In the second half of this year, we plan to announce the first high-level data readout in GBS following the completion of enrollment at the end of March. As discussed earlier, top-line data is expected later this year with a full data set, including the outcome from the comparative efficacy analysis to an externally matched cohort from the IGOS database expected to be available in 2024. Lastly, I want to highlight that we plan to announce five-year data from the long-term follow-up study in kidney transplantation from our four phase II programs, which led to the conditional approval in Europe.
The 5-year data is expected to be announced in the second half of 2023, during which time we also expect to publish the full data readout from the AMR phase II trial. Please turn to slide 12. This concludes our presentation, and we'd now like to open the call for questions. Operator, please begin.
Thank you. Ladies and gentlemen, if you'd like to ask a question, please press star followed by 1 on your telephone keypad now. When preparing to ask your question, please ensure your phone is unmuted locally. We have our first question comes from Christopher Nicholson from SEB. Christopher, your line is now open.
Hi there. Thanks for taking my questions. I guess, one thing that hasn't really been addressed so much in the presentation or the report was the news about the allocation system changes in some of the countries you're launching in. I guess, what I... Perhaps you can talk a little bit about that, just how broadly is that being applied? I guess, emergency use reimbursement, overcoming a culture of not transplanting across an immunological barrier, and on a backdrop of limited published outcomes data, competing with your own post-approval study, and kidney allocation have all been a lot of, you know, quite a lot of obstacles to getting a good ramp-up of Idefirix sales, right?
Is the allocation kind of the reorganization, the last big obstacle to expanded access or are there other things besides what I mentioned? That was my first question. Thanks.
Yeah. Thanks for this question there, Christopher. You know, obviously, as we've discussed on previous calls also, this is a launch of a transformative therapy into a market that is very, very complex. It's not just a question of making sure that the clinics are actually ready to use the product. You also need to look at the flow of organs, which is based on the, you know, different organ allocation systems that are in place throughout Europe.
Specifically, if I take that point first, you're right that if you look at the organ allocation system that is really relevant for countries like Germany and Benelux, the Eurotransplant organ allocation setup and system, a key barrier so far has been the fact that that has been based on compatibility and also finding a compatible recipient for an available organ with a range of kind of acceptable, you know, mismatch. Really now with the availability of Idefirix, the key question is, you know, who would be the most relevant patients to transplant and how do we ensure equity of access?
That necessitates for the countries that are dependent on the Eurotransplant program, a tweaking of the setup so that there is a list of patients that would qualify for organs that are not a, you know, a good match on appearance. That, that change will be implemented now in June is the latest that we've heard has been, you know, some months in process. That will open up then Germany essentially, the Netherlands, you know, as key countries. Even though we did have one transplant in the Netherlands, you know, we're really looking for this change to see, you know, repeat business and wider usage.
There are other countries where the Eurotransplant setup is not that relevant, like the UK. Still there is a delay from actually getting the reimbursement overall like we did in the UK. last year, negotiating with NICE and the National Health Service and all that. It has taken many months, and they're actually only ready now to develop local lend protocols, you know, what patients should be treated, would qualify, how should they specifically be treated in the clinics, who should be involved in this and so on and so forth. There are many delaying factors, if you will, in actually securing an uptake, which is why, as predicted, we've been talking about this S-shaped launch curve. It is slow-going in the beginning.
Now we expect the UK to begin to kick in now that the protocol is in place and the organ allocation system works in the UK. As I said, in Germany, we expect a change of becoming effective in June that will also impact the Netherlands and Benelux broadly and some other countries. France is moving ahead quite nicely, and that really demonstrates the value of having experience, right? We're very happy to get conditional approval based on phase II. What is a little bit tricky and challenging is the fact that obviously only 53 patients were included in phase II, and 46 of those were transplanted. France and Sweden were the two countries that actually had gotten some experience through that.
Now we're seeing the kind of the importance of getting that kind of experience, and that's why we're working in a very focused manner, including, as you mentioned, through the post-approval efficacy study to generate appropriate successful experience in key centers. As we mentioned during the call, we're now seeing also the effect in that we're getting repeat business in some centers. Thanks for the question, Christopher.
Thanks. If I could just a quick follow-up on that. Could you give us a bit more detail on the status of the post-approval study? I mean, in terms of the, you know, recruitment target. Also, when it comes to the cost base, so between now and 2025, when do operating cash outflows start to decrease from the current level to, you know, enable that into 2025 runway to be met? Also, can you give a bit of color on how to expect net financials to evolve going forward? Thanks.
Thanks for those follow-up questions, Christopher. First, on the post-approval efficacy study, current status is that we have enrolled less than 10 patients. We're in good shape there. The target is, of course, to have this study concluded by the end of 2025. As I said, this is a great way to generate relevant experience in some of the key centers here. As far as the financials are concerned, the cash flow through 2025 and what to expect, I'll hand over to Donato Spota.
Christopher, so for this year, obviously, as mentioned on the call and discussed previously, we do expect some ramp-up in costs for the reasons that we mentioned. When it comes specifically to cash flow, I would assume that starting from next year with then even higher sales than what we expect this year, the cash flow earn or cash flow should turn in the other direction.
We would see some reduction in the cash burn, everything else being equal, obviously. Then on the general, you know, cost base going forward for this year, I mean, I would like to point you then maybe to our consensus model that is available on our website. There, the EBIT for the year, the median EBIT for the year is estimated at SEK 635 million. I think that's probably a good ballpark. Also the patient uptake that is modeled in the consensus is probably something where we have no major disagreements.
Okay. Thank you very much.
Thank you. We have our next question comes from Gonzalo de Arteaga from ABG Sundal Collier. Gonzalo, your line is now open.
Hi, everyone. Thank you for taking the questions. I have a question also, a follow-up from the previous one on the Eurotransplant new allocation tier. It seems that it will allow patients that have been in the waiting list for more than three years to be candidates, let's say, to receive imlifidase. How many patients are these? I mean, is there any way that patients that are identified as sensitized not having for three years in the system to receive imlifidase? I mean, how can we picture this new allocation tier?
I cannot give you the specific number of patients, right. That really depends on what countries you include there and the availability of numbers varies quite a lot and the quality of that varies also quite a lot. But this is a significant number of patients. Again, unfortunately in Europe, the waiting time for patients waiting for a potential life-saving kidney transplant is measured in years on average, right. If you're highly sensitized, it's many years. Again, if you're highly sensitized, then you're more likely to die waiting than actually be transplanted. This is a very significant number of patients.
That's the fact that there's this, you know, we talk about this three-year limit is not a limiting factor. We're really looking forward to the impact that this change will have, which essentially will open up, as I said, very important markets like Germany and Netherlands and so on. That's important. In fact, if you just look at what to expect for the remainder of the year, as I said, we do have some nice activity in France. The UK is only now getting ready, and we can only now really expect there to be an impact from the UK.
I was at the British Transplantation Society's annual conference a couple of months back, met with all the key players, there's a high degree of excitement. They're really ready to get going. We expect that there will be a nice impact there. Spain, Italy, we just got reimbursements. It's very, you know, early, but towards the second half of this year, hopefully having then also gone through successful negotiations with the regions in Spain and in Italy, hopefully we'll see an impact from these markets. We had a launch effort in Rome in Italy. Very recently, I met with the key players in Italy.
Very impressed by the level of professionalism and the excitement and so on around this new opportunity to provide equity of access also for Italian patients. Hopefully, again, as I said, we'll see an impact in the second half of the year from Italy. We're right now seeing, you know, some of the necessary kind of infrastructure changes happening that will enable, you know, a growth in the transplants numbers.
Okay. Thank you very much. A second question is on the US ConfIdeS trial. I mean, it's this translation, let's say, from enrollment to randomization. I mean, how predictable is, I mean, how can we pre-predict like that those patients that enroll will be randomized in a matter of six months or something like that? I mean, how can we understand that, yeah, from the 62 patients that you have enrolled now, how many can we, assume that you will have randomized in the next month? I mean, is there any way to do that?
We're very focused on this. There is a, as we've discussed on previous calls, there is a delay, measured in at least a month and typically several months from enrolling to being randomized, again, because you need to be offered an organ through the US Kidney Allocation System. There is this delay. We have a, you know, double-digit number of patients that have been randomized. Now going forward, we expect to report the actual number of randomized patients. That is our key focus at this point in time, being so close to reaching the target of 64, even though we want to again over-enroll so that there's, you know, a sufficient number of patients quickly enough that are randomized.
As I said, what I can tell you is that currently there's a delay of some month from being enrolled to actually being randomized. There might even be some patients that will not actually be offered an organ within the study period, which is why it's important to over-enroll in the study.
Okay. Thank you very much.
Thank you. We have our next question comes from Douglas Tsao from H.C. Wainwright & Co. Douglas, your line is now open.
Hi. Good morning. Thanks for taking the questions. Just first, in terms of 5487, I'm just curious, how far along are you in terms of collecting an indication? I know you said it's gonna depend a little bit on the results that you get. I'm just curious, what exactly are you going to be focused on? In terms of figuring out where you want to first go, is it going to be safety? Is it going to be, you know, IgG levels? I'm just curious sort of what parameters are you most focused on. Then for Idefirix, for X, in terms of should we expect always the first quarter to be a little slower from a seasonality standpoint, or is that not as much of a factor for this product? Thank you.
Hi Douglas, thanks for those two questions. First on HNSA-5487. You know, I have to say we're really excited about the opportunity here. This is a, of course, a completely different molecule from imlifidase. It will hopefully enable a much more durable impact and also flexible impact on pathogenic IgG. That opens up really a very broad array of potential indications. Very exciting, important indications, not just in the autoimmune disease space, where we have previously discussed. Obviously, there's a range of IgG-driven, more chronic autoimmune diseases where there's really no good options available for the patients if they have flares and so on.
That's one opportunity, and we're fairly far advanced already also at looking at some of the diseases that could be relevant in that space. It's also very relevant in the gene therapy space. Now, as I mentioned earlier in this call, clearly with imlifidase initially and through our collaboration with Sarepta and Ask Bio, we're focused on preexisting neutralizing antibodies. There's clearly also a need to increase the durability of response. We've seen that with the gene therapy programs in the clinic that there are issues there. We expect that our platform and potentially our 5487 and other enzymes might really be very helpful there. And potentially we could also expect to be able to enable lower dosing of the AAV, right?
With all the improvements and benefits from a safety perspective there. So that's another broad opportunity for HNSA-5487. There is the area of oncology and not least the exciting area of hematopoietic stem cell transplantation, which we have previously discussed, and where there's a clear need to also look at these desensitization issues and so on. This is almost by default a kind of a multiple dosing setup and where you need flexibility and so on. That's certainly also something we're looking at.
We will based on what we get out of the phase 1 trial, and, you know, concurrent and parallel work we're doing, we'll be able to make the decision around, you know, what should be our priority 1 indication to go for. It's really a number of different things we're looking at, including, of course, safety, tolerability, efficacy, anti-drug antibodies, and so on. The second question you asked was regarding the launch in Europe and whether we expect seasonality. I think it's too early to really predict. I mean, but typically what you do see is that transplants are scheduled outside of holiday periods. You know, the Christmas period is not a peak period for transplantations.
Likewise, there might be some other holiday areas, but otherwise it's not really a seasonality kind of driven market. That's not the case. We do expect, you know, volatility from quarter to quarter.
Okay, great. Congrats on getting HNSA-5487 into the clinic. That's a great accomplishment.
Thanks. Thanks. We're really excited. Thank you.
Thank you. With our next question comes from Ingrid Gafanhão from Bryan, Garnier & Co. Ingrid, your line is now open.
Hi. Good afternoon. Thank you for taking my call, my question. I have a couple of questions regarding your new flow and pipeline in the second half of this year. We should see the flu data for the AMR trial plus the top-line data for IGOS. You already commented before you're starting to look at what you're going to do regarding the repeat dosing program. I was wondering, can you high-level explain what kind of data you're expecting to see for the, for the trials and how is that going to guide your decision on what programs to go forward with? Are you currently planning to bring all them all forward if all works out? Just trying to understand how you're going to prioritize based on the data that we'll see.
I take your last question as pertaining to 5487 specifically. I'd say overall, while there are many different opportunities and we're quite excited by the field of opportunities, obviously we need to prioritize for obvious reasons, especially in a capital-restraint environment. What we will be looking at is of course, you know, where do we see the biggest degree of unmet medical need and where we think that there is the highest likelihood of success for this particular molecule. That will be based on a number of different factors. Was that reply enough for your question there, or did you also have questions around the IGOS and AMR readouts?
Yeah, I think it will be interesting also to hear how you're thinking about those because what I'm trying to understand is what will be the sequence of events. Do you want to see the data for all these trials first before you make a decision to move forward? Or, yeah, do you see an actual opportunity to do further studies in all the indications that you are looking at right now?
Obviously based on the first readout from the AMR study, we've already initiated the discussions and dialogues, and we'll get the full data set, and as being reported, that will continue, right? We will make a decision there based on the outcome of those decisions, or sorry, discussions and associated decisions. As far as the GBS study is concerned, what we will report out this year is really around, you know, safety tolerability, potentially, you know, early effects of treatment in the GBS patients. Really the efficacy comparative data set will only be available once we've done the analysis versus, you know, the matched cohort from the IGOS database, and that will happen in 2024.
That will be a decision that we'll make in 2024, what to do as the next step there.
Okay. That was clear, Søren. Thank you very much.
Thanks, Ingrid.
Thank you. As a reminder, ladies and gentlemen, if you'd like to ask any further question, please press star followed by one on your telephone keypad now. When preparing to ask your question, please ensure your phone is on muted locally. We have our next question comes from Johan Unnerus from Redeye. Johan, your line is now open.
Thank you. Yes, a few questions, and I've been clarifying so far. Clearly the launch is a bit on the soft side, and would be good to get a feel for the level of dynamics and visibility ahead. You pointed to some markets where local protocols and reimbursements are in place or is about to be in place. Could you give us perhaps an indication of how many markets are in a more dynamic stage by second half of 2023?
Yes. You know, essentially now on paper, we have market access to the majority of the transplant patients in Europe, right? Now we have access in the top five markets. You know, more than 15,000 representing essentially more than 15,000 kidney transplants annually. As I've also indicated, there is a delay from getting the national level decision to actually pushing that through the regions and all the way down potentially to fund holders at the hospital level. We expect that to take place between now and, you know, the rest of the year, so that in the second half of this year, we certainly hope to have real access all the way through to patients in the top five countries.
That's why we do expect a clear backlog of sales this year. So far, I mean, it's been, as I said, we've seen very nice impact in France, you know, which was also one of the countries participating in our phase two trials. If we can replicate that in the other countries as they start getting online, you know, that's really very nice. Obviously there's a number of smaller countries where there's also some very advanced and leading kidney transplant centers.
Thank you. That's useful. Also, to what extent you can proactively make a decision and step up among these processes, perhaps, local protocol for so on or sharing experience. Do you need to add more supporting capabilities?
I mean, clearly, this is the responsibility of the clinics and the groups of clinics, you know, sometimes organized on a national level like in the UK. We have certainly been very much... If you look at what has historically taken place so far, we have certainly been very much consulted and involved, and we've been very pleased with the outcome. As I said, if I look at the UK, great protocol that's in place. There's a high degree of interest and conviction and desire to get going. We expect, again, similar kind of outcome in the other countries. I mentioned Italy before.
Spain is one of the leading transplant countries in Europe, with probably one of the best organ allocation systems in the world actually, and where a high proportion of the transplanted patients get their organ from a deceased donor. We do expect, you know, quite some material impact from these countries as they get online. It's impossible to predict, you know, specifically in what quarter and so on, but clearly in the second half of this year, we do expect impact from these large, you know, countries and some of the smaller ones as well.
If I may add to what Søren just said, I think what we're also aiming for is obviously to, of course, with the exchange of experience between those transplant physicians who have already used imlifidase in transplanting patients and those who are, you know, just about to start so that we get, you know, these experience across those hospitals who have are more advanced in the use of the drug versus those who are just, you know, starting with using it.
Good. Also the process from, it's more about a follow-up or clarification. In the US pivotal study, the process of moving from enrollment to randomization and to get allocation of kidneys, to cope with the ambition and the target to file by 2024. When do you need to have sufficient number of patients randomized? By the end of 2023 or?
That is critically important, obviously, to get a, you know, the 64 patients randomized by the end of this year, right? There's a clear focus on this and, you know, that will determine, of course, the ability to file a BLA later.
Yeah. Finally, the sub 10, the collaboration with Sarepta, clearly they have a due date now end of May. Are we likely to get a signal that the clinical study is starting soon after that or this happen anytime?
Johan, I think, I don't know if for some reason you're going in and out here. Can you repeat your question and maybe speak close to the mic?
Yes. Sorry. Do you hear me better now?
Yeah, a little bit better. Yeah.
Okay. I think this is better. They have a definite date by 29th or end of May. Clearly the next step.
Sorry. Hey, Johan. I don't know. I really can't hear you now, but it's something about May. Maybe we can take another question from the next caller, and then we can get back to you.
Thank you. As a reminder, ladies and gentlemen, if you would like to ask any further question, please press star followed by one on your telephone keypad now. When preparing to ask your question, please ensure your phones are muted locally. We have no further questions on the line.
Okay. Okay. Well, thank you very much, operator, and everyone, who's called into this conference call. We're very excited about the progress, and we look very much forward to keeping you updated. Thank you.
Thank you. Ladies and gentlemen, this concludes today's call.