Renee Aguiar-Lucander: Thank you very much. Next page, here we go. So some key takeaways for the quarter. So obviously the full approval of TARPEYO in the US reflecting a new label incorporating eGFR and with a much broader patient population was obviously the key event for this quarter. Data supporting this disease modification profile, the local mode of action, a long-term patient benefits of treatment with TARPEYO was, as you heard, shared at a recent nephrology conference. Q4 net TARPEYO revenues of SEK347 million, equivalent to $32.6 million, and total net product revenues in excess of $100 million for the year. And we also saw record enrollment numbers in the quarter, increasing quarter-over-quarter by more than 50%. Fredrik mentioned the positive cash flow from operations and the strong cash position of $94 million.
And obviously, we’ve seen the positive momentum from the nephrology market focused on the eGFR data, increased awareness of longitudinal data related to progression of IgAN patients, and positive patient experiences, including the ability, obviously, for patients to have intermittent treatments rather than being forced into chronic medication. And we believe that this will be — this disease-modding profile of TARPEYO will continue to drive significant demand for nephrologists and become the cornerstone of standard of care in IgAN. The total revenue guidance for 2024 are reflecting strong growth expectations of the range of $150 million to $180 million really concludes the events of this quarter and obviously looking into this year 2024. So I want to just close out this Q4 presentation.
I was saying that we are super excited about what 2024 brings as being the category leader in a growing market with a patient-centric message and we believe that the new label will certainly continue to drive demand and clear patient benefits. And so with that, I’d like to open up for questions.
Operator: [Operator Instructions] The next question comes from Maurice Raycroft from Jefferies. Please go ahead.
Maurice Raycroft: Hi, good morning. Thanks for taking my question and congrats on the progress. I was wondering if you can talk about assumptions and key drivers behind your revenue guidance of SEK150 million to SEK180 million for the year and how the 555 patient start forms in the fourth quarter? And what you’re seeing so far in the first quarter, how those numbers are factoring into your 2024 guidance?
Renee Aguiar-Lucander: Sure. So in terms of what we’ve done is we’ve kind of triangulated a couple of different ways to look at this. So obviously, in terms of the — what we’re expecting to see is basically kind of a little bit of a year of two halves, right. So we are not sure of how really kind of how quickly we can get through the kind of P&T committees of the payers and how quickly they will change the rules to really kind of comply with or to be aligned with the new label. So obviously, what we are expecting is that we might see some of that market access friction where actually physicians are writing prescriptions as per the label, but obviously, where payers are still applying the rules of the old label. So that is something where I think that, we are expecting to see strong growth in enrollment, but we are expecting that, that might take a longer period of time to actually convert those enrollments into revenues.
And this is something that is just a little bit of an unknown to us. I think the second half, we are expecting the second half to be strong. I think that — and where some of those market access friction should be resolved. I think that in terms of another item that is a bit unknown for this year is obviously when the KDIGO guidelines are going to be available. Our assumption really here has been that there’s been quite a lot of delays. It’s unclear when they will actually be coming out. And so our assumption really is that the KDIGO guidelines will not actually kind of come out until probably the second half of this year and maybe even fairly late in the year. So on that basis, we’ve also assumed that we’re not going to really see any benefit necessarily from the new KDIGO guidelines coming out this year.
In terms of the — the other thing that we’ve looked at is just really also looking at other launches and consensus expectations for other products in terms of the renal space. And so we think that this kind of guidance and particularly considering that, obviously, those other renal launches also involve chronic treatment that this type of kind of span that we’re in is very consistent with where those other launches either have taken place or where expectations are with regards to consensus for some of those other treatments this year. So this is really kind of where we’ve taken the input for some of this guidance. And so I think that we really want to make sure that we are on a very stable footing as to any kind of guidance that we’re providing with regards to the franchise this year.
Maurice Raycroft: Got it. And is there anything more you’re saying about first quarter so far? Is it as expected? Or I guess any more color you can provide on that?
Renee Aguiar-Lucander: So I think what we’re seeing is, and we’re expecting is we are going to have that kind of first quarter seasonality, in terms of I would not expect kind of the Q1 to be particularly strong because of that, because of that impact that we saw last year. And I think we’re seeing it so far this year as well. I think enrollments continue to be very encouraging. And so again, I think we’re seeing a lot of demand. And I think it’s more of that kind of structural issues with the kind of US payer system, et cetera, and changing of insurance plans, et cetera, that seems to be impacting some of that conversion. But that’s probably what I can say so far about the quarter.
Maurice Raycroft: Okay. And maybe one other question for me, and then I’ll hop back in the queue. For the P&T committees to get the updated label through that process, is there anything you’re doing to expedite the process? And how do you assess progress along the way?
Renee Aguiar-Lucander: So yeah, I mean we obviously, we started already to try to communicate with a lot of the P&T committees just based on the publication in The Lancet. But in reality, obviously, no one is really going to schedule any kind of P&T committees until they know what the label looks like and that there is truly a new label to discuss. So obviously, there has been quite a lot of interactions prior to this to try to kind of prepare for those meetings. But none of these plans really have to kind of take meetings or do anything or plan anything until you actually have a final label in hand. So obviously, we have, as Maria mentioned, we’ve added some resources in this area, and it’s obviously something that we are considering to be of high importance for the organization, obviously, these first six months.
Maurice Raycroft: Got it. Okay, thanks for taking my questions. I’ll hop back in the queue.
Operator: The next question comes from Vamil Divan from Guggenheim Securities. Please go ahead.
Vamil Divan: Great, thank you guys so much for taking my questions. If I could ask two just about sort of the broader IgAN market. And I’m wondering if you have any sort of updated thoughts? You obviously mentioned all the excitement at ASN, and I think just broadly speaking about more patients getting diagnosed and treated for IgAN now. So I’m curious if you have any sort of updated views on sort of the potential market size, especially in the US or you want to see globally for IgAN? And then second, is obviously really from emerging competition, so in the mid- to late-stage pipeline, specifically from the April DAF inhibitors. So I’m curious sort of if those to make it to the market in the next two to three years, how do you see those sort of impacting TARPEYO’s place in the treatment paradigm, if at all? Thank you.
Renee Aguiar-Lucander: Yeah, sure. So I think we are consistently, just a little bit of a kind of a repeated message really, I guess, from our perspective. But I think what we’ve seen consistently is that this obviously is not an acute disease, right? It is a progressive disease, and it does develop over a reasonably kind of long period of time, doesn’t have any kind of immediate mortality risks. So I think on that basis, I think a large part of that kind of IgAN population has probably not been treated particularly aggressively or potentially not at all, apart from really with ACEs and ARBs and other blood pressure-related medications. So I do think that the longitudinal data as well as some of the clinical trial data showing placebo group deterioration, all the patients that actually have that are on the kind of blood pressure-related medication or have already had reductions in proteinuria, which clearly do not seem to translate into kind of eGFR stabilization, I think that, that data is continuing to kind of make its way through the nephrology community.
And I think there is a really kind of active dialogue in terms of how should this kind of potentially impact the treatment paradigm. So I think that we are seeing a growing part of that market. But again, I think this will probably be a market that will develop and continue to grow really over time as some of these kind of — as more data really kind of makes its way into the peer-reviewed journals. And as I think nephrologists ultimately use some of these available medications and see actually what impact do these medications really have in real life. So I think that it is a growing kind of market opportunity for sure, but I think we still have a little bit of time until that’s reached its peak kind of potential. In terms of the pipeline, so I guess it’s always a little bit difficult to kind of make a lot of statements really on a small population in Phase 2b.
But I think that, obviously, from a kind of mechanistic perspective, assuming that everything lines up and actually some of these results are reproducible. And also, obviously, safety data is critical for this, I think that without really having that kind of whole picture of understanding what the product profile really looks like and therefore, not really understanding which patient population might be appropriate for that treatment, it’s quite a difficult question to answer. But obviously, as part of your first question, it’s also very difficult to know as these kind of treatments that are already available today continue to penetrate the population, it’s also very difficult to know actually what is actually the unmet medical need going to be in this patient population in 2027.
But I think from a mechanistic perspective, I’m going to hand over to Richard to give his view from that perspective.
Richard Philipson: Sure. Thanks, Renee. So I think it’s an interesting question. But with Nefecon TARPEYO, as we’ve spoken about many times, the treatment that’s been designed to target the Peyer’s patches in the distal ileum, and it’s a B-cell modulator in that region, and it has low systemic bioavailability, around 90% of Nefecon’s removed by the liver on first part of metabolism. And when we look at these other treatments, you mentioned the APRIL BLyS mechanism. I mean, these are systemic treatments, which are acting on a different hits, if you like, within the pathogenesis of IgA nephropathy. So taking those kinds of considerations into account and also noting what Renee has already said about we need to understand more about these treatments, they need to build up a greater understanding of the safety, et cetera, but all of those things being equal, there isn’t a fundamental reason why these treatments couldn’t be given together given that they’re acting in different places at different levels within the pathogenesis of the disease.
Vamil Divan: Okay. Thank you very much for the insights.
Operator: The next question comes from Yigal Nochomovitz from Citi. Please go ahead.
Unidentified Analyst: Hi team, this is [Carly] (ph) on for Yigal. Thanks so much for taking our questions. Maybe just a follow-up on some of your prior comments. Curious if you can talk a little bit more about the characteristics of patients being prescribed TARPEYO with respect to baseline proteinuria. I know you mentioned the market access piece that you’re working through, but curious if you’re seeing any shift towards increasing intent to prescribe to patients with lower baseline proteinuria with the updated label?
Renee Aguiar-Lucander: Sure. So I think in terms of what we’ve seen to date, I would say that obviously, because of the label that we had up until December, clearly, the language in that label said generally 1.5. So clearly, it wasn’t a cutoff. And so clearly, we’ve had prescribers and successfully also kind of obviously getting to patients below 1.5. But because of the label, obviously, overall, there has clearly been a shift to the more kind of advanced patient population or serious patient population. I don’t have a specific kind of breakout of how that kind of works, but I do know that obviously, overall, it has had that impact of having the shift. The label obviously just became available in December, and so actually, we have internally obviously produced material, trained our sales force, et cetera.
So we’re really just kind of have rolled that out fairly recently into the market. So it’s a bit early to kind of know to what extent, if at all, there has been any real impact from the label at this point in time.
Unidentified Analyst: Okay. Got it. That’s helpful. And then we wanted to ask about the Phase 2 data coming up for setanaxib in head and neck cancer. Just curious to know a little bit more about what you’re looking to see in that data set and what you think would be an attractive profile for potential partners for that program. Thank you.
Renee Aguiar-Lucander: Sure, I’m going to hand over to Richard to just describe a little bit about what the data readout is going to contain and then I’ll give you a sense of what I think might be comfortable.
Richard Philipson: So just as a reminder, this is a double-blind, randomized controlled trial where we’re giving setanaxib with placebo on top of pembrolizumab in patients with recurrent or metastatic head and neck cancer. And we expect to have the results, as Renee said, a little later in this half. And the primary endpoint in that study is change in tumor size. And we think this is an important endpoint in a study at this stage, development is a little bit more sensitive than just looking at response rates, for example, although we will also be looking at response rates. We will have data on progression-free survival. And we also hope to have transcriptomic data available at the same time as well. So that will give us a very comprehensive view of the clinical impact of the treatment and also the impact of the treatment at a tumor biology level.
And clearly, what we want to see a significant reduction in tumor size in patients who are receiving setanaxib on top of pembrolizumab versus patients who are receiving placebo on top of pembrolizumab. We think it’s a well-designed trial. There’s an appropriate number of patients in the study. I think we need to take also, I’ve talked about the primary end point, but we really need to take all of the endpoints into account and look at the impact of the treatment on the tumor biology as well when we’re understanding the benefits of the treatment.
Renee Aguiar-Lucander: Yeah. And I would just add to that, this patient population has a very poor outlook. I mean these are kind of relapsed metastatic kind of patients with head and neck cancer. And the first line treatment that really pembrolizumab has a very limited response rate of 15% to 20%. So in terms of talking to KOLs and getting some input from them, obviously, even kind of an increase of that to the kind of high 20s would certainly be considered clinically very relevant. So I think that, both as Richard mentioned as well as kind of progression-free survival, I think that would kind of be the, taken together is really, I think, what people would be looking for in terms of this being a highly successful study.
Unidentified Analyst: Okay, great. Thanks very much.
Operator: The next question comes from Rami Katkhuda from LifeSci Capital. Please go ahead.
Rami Katkhuda: Hey guys. Congrats on the updates and thanks for taking my questions as well. Two quick ones from me. First, the language on the label for Kinpeygo is a bit more strict than what we saw with the accelerated approval of the asset in the States. I guess you expect there to be a difference in label language for a full approval as well.
Renee Aguiar-Lucander: You’re absolutely correct. And I think it’s always difficult to know how the two regulators are going to kind of actually assess the same data. They don’t always see eye to eye, they don’t always agree. But certainly, our hope would clearly be that the label on Kinpeygo is very similar to, if not the same, as the label in the US.
Rami Katkhuda: Got it. And then I guess if the open-label extension data is positive as well, is there a potential for the recommended duration of therapy language to kind of be removed from the TARPEYO label?
Renee Aguiar-Lucander: So I think that obviously it’s something that we have been discussing, and I think we’ll continue to discuss, I mean, when the right time is to maybe kind of go and have some interactions with the regulators, both based on kind of real-world data that we’re observing as well as some of the data from our clinical trials and potential data in other kind of Phase 4 studies. So there is certainly something that we are keeping in mind as to when we have the appropriate amount of data or the type of data we think is relevant, we certainly intend to go and have additional interactions with the regulator.
Rami Katkhuda: Got it. I guess do you guys know what percentage of patients currently are on treatment for less than or greater than nine months?
Renee Aguiar-Lucander: No. You mean like overall? I don’t actually. No.
Rami Katkhuda: Okay, no worries, thank you again.
Renee Aguiar-Lucander: Thank you.
Operator: The next question comes from Annabel Samimy from Stifel. Please go ahead.
Annabel Samimy: Hi, thanks for taking my questions. I had a couple here. I guess in terms of the enrollments, you saw a nice pickup. Do you have any sense to the extent to which the pickup in enrollments was from the new prescribers versus your older prescribers who’ve just seen the eGFR data? And I guess with the data, how much can we see the enrollment pick up from there? I understand that it may not necessarily translate into sales, but perhaps the enrollments continue. So that’s our first question. And then the second question is related to the magnitude of KDIGO guidelines. Are there any analogs that you have that could sort of help us, I don’t know, sort of more quantify what the impact of KDIGO could have on an uptick in sales? Or is it just still primarily all the payers that are the gatekeepers here and that’s pretty much who we have to count on. So I guess those are first questions, and I have a follow-up after that also.
