Calliditas Therapeutics AB

STO:CALTX

Earnings Call Transcript 2022-Q4

[Operator]

Welcome to the Calliditas Therapeutics Q4 report. [Operator Instructions]  Now I will hand the conference over to the speakers CEO, Renee Aguiar-Lucander CFO, Fredrik Johansson, Andrew Udell, President of North America; and Richard Philipson, CMO.

[Renée Aguiar-Lucander, executive]

Welcome to the Calliditas Therapeutics Q4 report of 2022. I would ask you to turn the page and initially just bring your attention to our disclaimer page, -- this is just related to forward-looking statements, and I refer you to the company's reports and other filings, including those which contain risk factors and other relevant information. We can go to the next page. So thank you for joining us for this fourth quarter report of 2022, which concludes a very successful year for Calliditas in which we commercially launched the first ever approved medication IgA nephropathy in the U.S. There has been great interest from nephrologists for medication, which targets the pursued origin of the disease and which does all the potential of being disease modifying based on early and significant impact on eGFR in patients at risk of rapid disease progression. To further support our top line data, which we presented in late 2020, we published a full overview of the Part A data in October of 2022 in Kidney International, which was met with enthusiasm from physicians who took a special interest in the continued reduction of proteinuria in all patients who have been off drug for 3 months after the 9-month initial treatment and the stabilization of eGFR patients at risk of rapid disease progression. Based on the many interactions with nephrologists at ASN, it became clear that EGFR data as it becomes more and generally more available, this will clearly die their treatment decision as their treatment goal is obviously to preserve kidney function over their patients. We're therefore excited as we approach the completion of the confirmatory portion of our Phase III trial.We can go to the next page. From an overall corporate perspective, we reported total revenues in Q4 of SEK 429 million, it's equivalent to approximately $42.4 million. outage truck payer sales represented NOK 167 million or about $16.1 million. For the year, that took us to total revenues of around SEK 803 million, equivalent to about $79 million, again, out of which Tapio represented SEK 372 million or $36.8 million. We're very proud of this result, especially in a market that actually was defined by strong macro headwinds, including volatile capital markets, high inflation, increasing interest rates and unfortunately an ongoing war in Europe. Against this backdrop, we have been able to over the last 18 months or so, raised over NOK 1.2 billion of non-dilutive capital, ensuring a successful launch of a first-in-class product into the U.S. market. I do truly believe that we have a lot to be proud about for 2022. We did decide during the year to also expand our U.S.-based sales team, and we have recently also brought them in-house into Calliditas. And we've clearly seen that this expansion has already had an impact towards the end of the quarter. We obviously continue to educate nephrologists as to obviously in the U.S. market today. We have an oral product, which can be added to physicians' choice of optimized applicate and which is based on a well-characterized active ingredient with a differentiated approach of targeted treatment of the origin of the disease with a goal of specific down-regulating IgA . We believe that this has the potential to be disease-modifying based on our early data, and we do look forward to being able to share longer-term eGFR data from our Part B readout.We go to the next page, please. So in December, we also reported that we had out-licensed Nefecon to Biatris for the Japanese market. This resulted in a $20 million upfront payment with additional $80 million of development, regulatory and commercial milestones. We're very excited about being able to further expand the global franchise of Nefecon and look forward to work with our new partners. In November, our other partners, Ivers Medicines had their China NPA filing accepted. And in December, also the regulatory body recommended a priority review from Fin China, and we look forward to having some results from that regulatory review towards the second half of this year. And as you may know, there are a lot of patients -- biosuperime patients in China, the Chinese market. This is a very, very significant unmet medical need, and we look forward to working with our partners, Everest Medicines to hopefully be able to address that need once the regulatory view has been completed. In terms of our pipeline, we reported in the previous quarter that there has been a slowdown in terms of site activation. I'm happy to report that those have kind of picked up and ecruitment rates in our head and neck cancer trial is significantly improved, and we are presently targeting the delivery of the biomarker data as we previously have guided on in this year. And we're hoping to be able to do that sometime around the middle of the year, obviously, depending on final arrangements for that readout. The PBC trial does remain challenging, and we've implemented a range of activities in Q4 and Q1, and we will continue to work hard at trying to address somewhat of the issues around kind of the somewhat slower rerecruitment rate than what we would like to see. In terms of further kind of financial highlights, obviously, we did in this quarter reported positive operating profit in Q4 of about SEK 32.5 million and obviously also a positive cash flow from operations. We -- that leaves us with a very strong financial position for the end of the year, with cash amounting to over 1 billion [00:06:53] -- almost 1.250 billion in SEK and around $119 million. We believe on that basis, we're funded to profitability based on continued delivery of sales from Trapelo and the Nefecon franchise globally.In terms of some post-period events, if we go to the next slide, please. Thank you. So in February, the MHRA announced that they had granted a conditional market authorization of Campego for the United Kingdom. And that CMA is in process of being transferred to our European partner, STADA, who obviously holds the commercial rights for that area. And also, obviously, based on the data, the completion of the last visit by the last subject in our Phase III trial NefIgArd. We now have a clearer view of when we will be able to share with you the top line data of our Part B. And so we are presently targeting somewhere around the middle of March in order to be able to provide that information. This readout will obviously provide long-term eGFR data, complementing really the eGFR data that we saw at 9 months, which was both statistically significant and clinically meaningful. For the year of 2023, we believe that on the basis of the -- what we're seeing in the market and some of the other points that Andy will be covering with you. We believe that we will have a U.S.-based revenues from tarpeyo, somewhere between $120 million to $150 million. And we believe that strong top line data from Part B could provide momentum to this uptake as the long-term eGFR data certainly will provide further insight into the potential disease-modifying activity of Tarpeyo. So with that, if we go to the next page, I will hand over to Richard Philipson, our Chief Medical Officer, who will take you through a little bit more detail around the Kidney International publication, which I mentioned in the beginning and which obviously has generated a lot of interest broadly in the nephrology area.

[Richard Philipson, executive]

Thank you very much, Renee. So if we move to the next slide. So I share Renee's delight that the results of Part A of the NefIgArd Phase III clinical trial were published online in Kidney International on the 9th of October of last year and subsequently in this year's issued 2 of the print version of the journal. I'd like to summarize the results presented in the publication. So moving to the next slide. As a very brief recap, Part of the NefIgArd trial enrolled 201 patients with IgA nephropathy and randomized them in a 1:1 ratio to receive Nefecon 16 milligrams once daily or placebo for 9 months with 3 months of post-treatment observation of treatment for patients continued into part B of the study, which comprised a further 12 months of treatment. All patients were on optimized RAS blockade with median baseline proteinuria and eGFR, reflecting a population of patients at high risk of kidney disease progression. After 9 months of treatment, those a highly statistically significant 27% reduction in proteinuria measured by UPCR in patients receiving Metacom compared to placebo with stabilization of eGFR and a 3.87 ml per minute treatment benefit compared to placebo. When we look at the 1-year eGFR slope improvement, which compares the eGFR slope in patients treated with Nethacon versus those treated with placebo, we see an improvement of 3.37 ml per minute, representing a preservation of eGFR of approximately 70% of the maximum possible effect. This effect is consistent as it is in line with what we saw in the Phase II study. And importantly, it compares favorably with other treatments studied in IgA nephropathy. For example, treatment with the SGLT2 inhibit dapagliflozin in patients with IgA nephropathy results in a calculated preservation of eGFR after 12 months of only 26% of the maximum possible effect. The safety of the treatment was in line with what was expected for a targeted release formulation of budesonide. And importantly, there were no severe infections requiring hospitalization. So in summary, overall treatment with Nefecon resulted in clinically important improvements compared with optimized supportive care alone.So moving to the next slide. An important observation relating to the effect of methaqualone proteinuria in the Part A study population is that the effects were not immediate with no discernible effect following 3 months of treatment, rather the effects become apparent at 6 months with a continued and cumulative improvement at 9 months. A particular note, Proteinuria continued to improve even after treatment had been discontinued in 9 months. So at 12 months after 3 months of treatment, there was a 52% reduction in Proteinuria versus baseline. Moving to the next slide. When we look at improvements in proteinuria associated with treatment with Nefecon, we see an interesting observation in patients with higher levels of baseline proteinuria. Specifically, we see an earlier separation of the proteinuria curves, so that after only 3 months, there was a 14% reduction in proteinuria in methaqualone treated versus placebo-treated patients. It's nevertheless important to emphasize that all patients in the methaqualone treated group showed improvements in proteinuria, irrespective baseline proteinuria levels. Moving to the next slide. This earlier improvement in proteinuria translated to early and divergent eGFR curves in these patients. EGFR declined by over 10 ml per minute over the 12-month period in the placebo group compared to a reduction of only 1.1 ml per minute in the Nefecon group, a difference of nearly 9 ml per minute at 12 months. Again, it's worth noting that EGFR remains stable during the 3-month follow-up period when patients have discontinued treatment with no evidence of deterioration in eGFR during this 3-month follow-up period. And moving to the next slide. So in summary, for the Part A data, Nefecon met primary and key secondary endpoints in the NefIgArd Part. The effect of methaqualone on proteinuria, gradual and cumulative with continued improvement after discontinuation of treatment. And in patients with higher baseline proteinuria, an earlier beneficial effect on proteinuria is observed, which translates to clearly divergent eGFR trajectories with stabilization of eGFR in Nefecon-treated patients. So that concludes my part of the presentation.

[Andrew Udell, executive]

 Thanks, Richard. Slide 15, please. The fourth quarter was another strong quarter to finish the first calendar year of the commercialization of [Indiscernible] Quarterly net sales of more than $16 million brings us to $36.8 million in net sales after the first 11 months of promotion. We had 310 new patient enrollments in the quarter, which has the 2022 total more than 1,000 enrollments, which were written by over 640 unique nephrologists. In addition, we continue to see the average enrollments per prescriber growing, and we anticipate this rate will continue to grow as many of the nephrologists now have patients on therapy for several months and experiencing positive results as was demonstrated in our clinical trials that Richard just reviewed with you. As it relates to market access, as mentioned last quarter, we really reached our target of over 90% of U.S. lives having coverage for a payout in the middle of the year, which we are very proud of. The payer mix has reached a steady state without much change from the last quarter. Approximately 3/4 of our patients had either private commercial insurance or cash-paying customers, with the remainder of our business coming from government insured patients. Tarpeyo touchpoints and the high quality of our patient service programs are extremely important to us and continue to exceed industry standards. Nevertheless, we continue to assess our program to identify areas of improvement and to determine if additional resources are needed to maintain this high level of service during a period when our patient population continues to grow. Our targeted reach and promotional programs remain effective, as demonstrated by the awareness of Tarpeyo growing to over 90% of nephrologists and market research surveys conducted prior to the end of 2022. Most important and rewarding to us during the fourth quarter and early this year are the increasing number of success stories that are being reported as more and more patients have taken Tarpeyo for extended periods of time.Next slide, please.. 2023 promises to be another exciting year of growth for Tarpeyo and our commercial organization. While we felt the initial positive impact of the expansion of our field during the fourth quarter, we look forward to the full impact from the impressive commercial team that we've assembled. -- Tarpeyo demonstrated a clear reduction in proteinuria and the early impacts on EGFR demonstrated in[Indiscernible]are unprecedented and extremely important. In addition to the increasing positive patient experiences we, along with the nephrology community anxiously await the results of Part B to gain increasing information on the lasting impact of Tarpeyo on this chronic kidney disease. We anticipate this information in the first half of 2023 and look forward to sharing the results with nephrologists and the iGame community. Lastly, we are enthusiastic about the progress and availability of Torpeyo in the U.S., Compego in Europe and Nefecon as it grows around the globe. IgA nephropathy is a rare orphan disease and the global patient KOL experience and education will be important in the continued growth and success of the brand and our company. And with that, I'm going to turn it over to our CFO, Fredrik Johansson.

[Fredrik Johansson, executive]

Thank you very much, Andy, and good afternoon and good morning, everyone. I will first present to you the financial overview for the fourth quarter of 2022 and thereof to present the full year numbers for 2022. As always, all numbers presented to you are in million SEK, unless otherwise stated. To start with, we are proud to report SEK429 million in net revenues for the quarter. For the same period last year, we reported net revenues of $31.2 million. In the fourth quarter of the pay of commercialization Tarpeyo product sales for the quarter amounted to $167.3 million or $16.1 million, a growth of SEK 36 million, 36% compared to the third quarter. In addition, we also recorded SEK 26.2 million for the period in revenues related to transaction with our partners, especially from the USD 20 million signing fee from the Viatris out license deal, but also from a $5 million regulatory milestone from Everest relating to China. Our total operating expense for the fourth quarter amounted to SEK 388.7 million compared to SEK 253.3 million for the same period last year. Compared to the third quarter this year, our OpEx did increase by around SEK 96 million from Q3. And this increase is mainly due to certain costs related to the marketing activities were concentrated into Q4 instead of spread out of both Q3 and Q4. Certain onetime costs and also a cost increase in the quarter from our expansion of our sales force in Q4. I'm very pleased to report that our increased revenues for the quarter led to an operating profit of SEK 22.5 million for the fourth quarter compared to an operating loss of SEK 280.5 million for the fourth quarter 2021. In the fourth quarter, we also had a positive cash flow from operating activities of SEK 230 million compared to a negative cash flow used in operating activities of SEK 161.3 million for the same previous year. And the positive cash flow was mainly achieved through -- we received payments in the quarter from our licensing activities and from the increase of the Tarpeyo sales.In the fourth quarter, we also made a last drawdown of $25 million from the Krios loan facility, which is now fully utilized, bringing our cash flow from financing activities in the fourth quarter to SEK 282.6 million. This leaves us with a net increase in cash in the quarter of SEK 511.2 million and a very healthy cash position at the end of the quarter of SEK 1.249 billion. And we take the next slide -- just a quick summary of the financial key takeaways from the full financial year of 2022. For the full year of 2022, we are very happy to report SEK 82.9 million in net revenues for the period. This is a growth of 250% for the year compared to 2021, where we reported revenues of SEK 229.3 million. Tarpeyo product sales for the year amounted to SEK 372.2 million or $36.8 million revenues related to outlying transactions and royalties were SEK 427.4 million compared to reported revenues from our placing transaction for the full year of 2021 of SEK 229.3 million. Our total operating expenses for 2022 amounted to SEK 1.296 billion compared to SEK 753.8 million for the full year of 2021. Out of the total operating expenses for the full year of 2022, marketing and sale expenses increased by SEK 335.6 million to SEK 515.2 million compared to SEK 19.6 million for the full year of 2021. The increase in marketing and selling expenses originated from the commercialization of Tarpeyo the U.S., including our sales force compared to 2021 when we were in preparation mode only prior to the start of the commercialization. The cost for research and development for 2022 increased by SEK 57.2 million to SEK 44.7 million compared with SEK 37.5 million for the previous year. The increase in R&D expenses originates primarily from the ongoing operations for the CETX trials. The cost for administration for the full year of 2022 increased by SEK 48.9 million to SEK 259.5 million compared to SEK 210.6 million for 2021. The increase in cost between the years was primarily related to general cost increase for administration due to organizational growth, increased cost for compliance and increased complexity being a company in the commercial stage. Our operating loss improved by SEK 102.5 million and amounted to SEK 421.9 million for the full year of 2022 compared to an operating loss of SEK 524.5 million for 2021.The cash flow used in operating activities for the full year of 2022 amounted to SEK 311.4 million compared to SEK 461.6 million used for 2021. Our cash from financing activities were SEK 576 million for the full year of 2022 compared to SEK 435.2 million for 2021. This leaves us with a net increase in cash for 2022 of SEK 259.5 million compared to a net decrease in cash for 2021 of SEK 50.8 million. And finally, and again, we are very happy with the cash position of SEK 1.249 billion at the end of the year. That was all for me. And now back to you, Renee.

[Renée Aguiar-Lucander, executive]

Thank you. So as I mentioned upfront, 2022 was a very successful year for Calliditas . We saw overall revenue growth in 2022 of 250%, reaching over SEK 800 million, which shows obviously strong revenue from the year both from product sales and partner income. In terms of the Tarpeyo revenues, it came in line with our guidance, which we had provided of around $37 million for the year and $16.1 million for the quarter. There is clear excitement in the nephrology area around our ability to being able to share our Part A data was very clear from interactions at the ASN -- and I think it is considered very interesting in terms of the specifics of the data, which Richard covered previously, which seems to stand out from other product -- potential product candidates. In terms of the sales force, as we mentioned, we did expand this towards the end of the year. And so we are seeing continued penetration into the prescriber base and look forward to having continued growth in uptake in 2023. In terms of commercial partnerships, obviously, we mentioned in Japan, we would be outlicensed epacontoviatrist in IgA nephropathy, obviously, an additional kind of nondilutive cash rate of $20 million, but also, obviously, very importantly, we look forward to work with our new partner and expand the Nefecon global franchise.In China, as I mentioned, the NDA was accepted and towards the end of last year, and we're looking forward to the regulatory review process and the ultimate decision, which we expect to happen towards the second half of this year. In terms of guidance, obviously, we mentioned that based on these patients, we are seeing really kind of the beginning of patient success stories, peer-to-peer recommendations in the market, that kind of momentum in combination with streamlined market access, the published data that came in towards the end of last year. So we're expecting net sales of our Tarpeyo in the U.S. of between $120 million to $150 million. And with that, that concludes the presentation, and we're happy to take any kind of questions.

[Operator]

[Operator Instructions] The next question comes from Maurice Raycroft from Jefferies.

[Farzin Haque, analyst]

This is Farzin on for Maury. You are projecting a strong $120 million to $150 million. So can you walk us through the assumptions that went into it like potential treatment duration beyond 9 months PSS use sales and potential competition to from Travere getting approved?

[Renée Aguiar-Lucander, executive]

So I think that, obviously, there are multitude of variety variety of kind of inputs into that estimate. But I think that, obviously, it is based on, as I kind of briefly mentioned, we are now having patients on drug for a longer period of time. We're hearing a lot more about kind of patient successes, physician successes, there's a more -- there's a buzz in terms of peer to peer recommendations and obviously, also the data that fairly recently got get into the market from our kind of publication. So I think that there is -- and obviously, we are expecting additional kind of data this year, which we also believe can impact the momentum of the uptake. Very specifically in terms of exactly when these kind of -- when the momentum really picks up and how it goes, it is difficult to to judge. But I think in terms of any other kind of potential approval, we don't really think that's going to have any real impact on our kind of projections for 2023.

[Farzin Haque, analyst]

And then the other question is on the expectations for the eGFR data from the Part B like and how much and how you think it will impact the label from a disease modifying caim perspective?

[Renée Aguiar-Lucander, executive]

Yes. Well, obviously, that's going to really be judged in conversations with the FDA and EMA. And so I think that will truly just depend on kind of the strength of the data that we see coming out of that trial.

[Operator]

The next question comes from Annabel Samimy from Stifel.

[Annabel Samimy, analyst]

Congratulations on the progress. So just in terms of the success stories that you're hearing and some of the anecdotals, have you started seeing patients staying on drug for longer than 9 months, I mean the drug has been out for, I guess, about a year now. So I think you can have some metrics around that. So are you seeing them stay on drug beyond 9 months? Are there restrictions around patients getting treated if they're responding well and just a little bit of color around that. And then when you think about the EGFR data, if it's positive, -- do you have any additional initiatives for new educational efforts around that to change the label and for work with payers and potentially improving terms or ease of onboarding or facility if that data actually comes out positive? Any kind of work that you're doing there to streamline the process?

[Renée Aguiar-Lucander, executive]

Great. Andrew, do you want to take the first part?

[Andrew Udell, executive]

Yes, sure. So I'll comment on the duration of therapy. You're absolutely right. We are now seeing patients that have been on therapy greater than 9 months, while it's obviously the first patients that are on product. But the good news is what we're seeing is it really seems to be determined by the physician. -- right? This is a heterogeneous progressive disease. And as we've always said, we want these decisions to be made by the nephrologists, the treating physician. And so we are seeing that. We have definitely a good portion of patients that are on for more than 9 months and some that stop at 9 months on treatment. I think this is going to be based on patient to patient. And like you said, the market access, it hasn't been a barrier to this. And so these patients are able to continue as long as they qualify, and they're still taking their medication there.

[Renée Aguiar-Lucander, executive]

In terms of kind of the EGFR data point that you mentioned, obviously, yes, we do have quite a lot of activities in preparation for that data. And yes, I mean, obviously, that will be a kind of a separate FDA review with a full kind of 360 patients and obviously, with the endpoint as communicated in terms of EGFR. So yes, our expectation is that, that may very well lead to expansion of label or a different label because, obviously, we would be able to kind of have slightly -- we will have different data to support some of that development. And I don't know, Andy, if you have any additional comments on the market...

[Andrew Udell, executive]

Yes, sure. So Part A, once it's published or Part B, I should say, once it's announced and then published, there is -- we are permitted to share some of this information certainly with payers in confidential. I think we've been very pleased with our management to date, but certainly, obviously, we could only improve from there with positive data. So we do anticipate sharing it as soon as possible. And hopefully, that will have some even further favorable treatment.

[Operator]

The next question comes from Yigal Nochomovitz from Citigroup.

[Yigal Nochomovitz, analyst]

 Renee, can you comment -- I know it's early in the launch, but can you comment at this point on what your market share looks like in the United States and you referenced some of the statistics for the prescribers, 642 and the enrollment 2039. -- can you connect that to your guidance in terms of how many prescribers you would expect by the end of 2023 and the number of enrollments by the end of 2023?

[Renée Aguiar-Lucander, executive]

So obviously, what we've said before is really, I mean, when we're looking at when we've done our mapping, our market research on other work before we kind of launched, we really identified that probably the prescribing integration is kind of the most relevant for us would be around 3,700 to 4,000 nephrologists -- so obviously, from that perspective, we're really only kind of -- we have a very small amount, we're really kind of scratching the surface in terms of where what we can do with regards to that based on where we are on our first kind of 11 months of commercial activity. But obviously, there is -- in the actual kind of enrollment in prescribers, there's obviously this combination of refills and actually kind of patients staying on drug is then well new enrollments, et cetera. And obviously, then when those enrollments actually happen. And so I think it's very, very difficult at this point in time to kind of share that because it's a multitude of factors that go into that.

[Yigal Nochomovitz, analyst]

Okay. And then just on the duration question. Is it fair to assume that pretty much everyone that's starting is going through the 9 months? Or is there a discontinuation rate that you're observing this for some patients is less than 9 months?

[Andrew Udell, executive]

I think it's hard to answer that, obviously, because patients are continually moving through the process. But I think as far as discontinuation rates, it's probably similar to assume similar to our trial in Phase III. That's probably the best I can give as far as estimates on discontinuation rates.

[Yigal Nochomovitz, analyst]

 Okay. And then just going back to the Part B data, I mean, sort of as before but maybe ask in a different way. Could you kind of characterize how you would frame the base case for what that EGFR data would look like? What would the bull case look like for that data readout? And also what might be the less optimal bear case for that readout...

[Renée Aguiar-Lucander, executive]

So I guess, obviously, I mean -- so we're looking for 2 things, obviously. One would obviously be to kind of see the duration or durability of the proteinuria reduction. We do have the 3-month kind of already kind of across all patients that we're seeing between the 9 and the 12 months. And then so the question is really, will that be persistent across the entire population, some of the population? Because obviously it is a heterogeneous group of patients or we know that they kind of develop in heterogeneous way. But I think, obviously, the longer we can see that kind of protein reduction or continued reduction, I think, obviously, that would make us -- that would be kind of go towards a stronger and stronger case, the longer that we can show that. In terms of the other aspect is obviously then eGFR. And I think, obviously, again, the longer that we can show that there is kind of a difference in eGFR kind of trajectory between kind of the treatment group and the placebo group, then obviously, again, that goes towards kind of disease modification. So I think that those are kind of the old views kind of directionally what we would find would be will we be looking for kind of in the trial. And then I think it really comes down to is this really kind of a very homogeneous population. Is it heterogeneous, -- we're going to see slightly different kind of things depending on kind of what type of profile these patients had when they came into the trial, et cetera. So I think that would really kind of be my view. I don't know, Richard, do you have anything to add?

[Richard Philipson, executive]

No, I don't think so. I think that really summarizes the position pretty nicely, actually.

[Operator]

The next question comes from Dan Akschuti from Pareto Securities.

[Dan Akschuti, analyst]

Congratulations from the great programs with Tarpeyo and also on the upfront and milestones received from global partnerships. So my first  question is that do you see a need to increase the sales force further, considering the competitor sustained FDA approval that will start with a bigger sales force.ÂÂ

[Andrew Udell, executive]

So we assess this kind of information at different points. And currently, there's no plan to increase our sales force. But I would say that if it made sense in optimizing the product and the brand, we would certainly would consider doing so at some point, but there's no set plans on doing so at this point.

[Dan Akschuti, analyst]

Regarding the European market, could you provide some thoughts on the sales uptick? Is the sale fully reflected on the royalty income in '22? And do you have any discussion with that you are able to provide?

[Renée Aguiar-Lucander, executive]

Andy, do you want to add to...

[Andrew Udell, executive]

 Sure. I think that the information is our partner is pleased with the uptake to date. They launched in September and data shows that they have just shy of about 70 patients on therapy before the end of the calendar year, which puts them on mark for where they estimated they would be, and they feel very encouraged at this launch so far in Germany. I didn't hear the second part of the question. Can you repeat that?

[Dan Akschuti, analyst]

So is that all fully reflected on the royalty income in '22? And do you have any detection that you are able to provide. So yes, that's pretty much it. And -- sorry, and the last question is the R&D cost is over SEK 100 million. Can we expect that to remain stable over the coming years? And what is the strategy with that a flip in the next stage to plan the partner or to plan to finance both indications by yourself?

[Andrew Udell, executive]

So --sorry, can you repeat that...

[Renée Aguiar-Lucander, executive]

 It was R&D costs? Are we expecting -- if I understand you correctly, you're asking if the R&D costs are going to stay the same. Is that -- was that your first part of the question?

[Andrew Udell, executive]

We would expect it to stay in the ballpark basically. We do have a new program with Alport, which will increase the cost a little bit, but there will be no material increases for this year, we think.

[Renée Aguiar-Lucander, executive]

And in terms of kind of our kind of ongoing plans for kind of doing development ourselves or with partners, which I believe was your second part of the question. And obviously, what we've communicated before is obviously, if there are rare disease programs, and obviously, Alport is something that fits very well into our existing franchise. It's a renal asset. There is really nothing approved in all course. They're really significant unmet medical need, and we're super excited about being able to start that clinical trial. And obviously, PBC is another rare disease where we believe that we could commercialize that ourselves. Again, not in all geographic territories, but in select geographic territories. Head and neck cancer is obviously different because that really is a parallel kind of if you want to call it parallel path that really is more to characterize the mode of action of this drug because there's so much kind of preclinical data that exists in head and neck. And to the extent that the biomarker data that we read out if we get very strong biomarker data from that trial, we would not plan to take that R&D effort onwards, which would then go into potentially several kind of solid tumor types and would be a very, very significant R&D program. So we would then look to really partner that asset to the extent that there would be strong data, and there will be interest from big pharmacy to do so.

[Operator]

The next question comes from Ingird Gafanhão from Bryan Garnier.

[Ingird Gafanhão, analyst]

I have a couple actually. So first on the price, I know you disclosed the 14.20 sort of in the beginning of next year. Should we expect any price increase for this year? And what would be a reasonable number to you soon? And then I have a follow-up.ÂÂ

[Andrew Udell, executive]

So we did take a price increase at the end of January of 6.8%, in line with increased costs and inflation in those type of factors that go into these kind of decisions.

[Ingird Gafanhão, analyst]

 I think for a follow-up, you did mention that you're still quite far for reaching the number of unique prescribers that you have for your target physicians. At the moment, what is keeping you from actually increasing this number a little bit faster? Is it a matter of sales force size or just time did you need to get to those accounts?

[Andrew Udell, executive]

This is a rare disease. So that's not -- they don't see the patients every day. We see the physicians and it's a process that they go through. It's an educational process. No one's talked to them before about IgA nephropathy, the source of the disease, and this data is unique to them, seeing something like this. So it just takes time. different physicians have different adoption rates. -- some are adopting slow as far as one patient at a time where others put multiples on. So I don't think it's -- I think it's going very well. I don't think it's slower than we thought as far as reaching our target. You have to cast this wider net to get these prescribers on board.

[Ingird Gafanhão, analyst]

 And if I may ask one quick last question on the financials as well. So you mentioned that you have enough cash to reach profitability. And would you feel comfortable with saying when that could be possible or how you're looking into that?

[Andrew Udell, executive]

No, we will not specify specify a specific time point given that we -- I mean, as you see, we do have a certain range in our guidance and also we would -- we are also starting the Alport program. So adding on a little more cost to it. So we are not specifying that to a specific quarter.

[Renée Aguiar-Lucander, executive]

But it is clearly kind of our direction and our focus, obviously, to get there. So I mean, that hasn't changed at all. It's just difficult to kind of, again, know when this momentum is really going to pick up. It's kind of peer to peer, and when we're going to start seeing that kind of -- which we have started to see, but it's difficult to kind of judge exactly the impact of that. So -- but our kind of focus and direction there is obviously still clear.

[Operator]

 The next question comes from Rami Katkhuda from Life SCI Capital.

[Rami Katkhuda, analyst]

 Congrats on the progress. Two quick ones for me. But in your guidance, do you expect net sales of Tarpeyo to kind of continue linearly growing? Or is that an inflection point going to be around successful Part B data or full approval by the FDA, et cetera? And then with regards to market access, are you seeing big differences between commercial and Medicare lives or our coverage in prior as similar across the board?

[Renée Aguiar-Lucander, executive]

 So I think that to some extent, uptake is partly organic. It's this is kind of based on just kind of education and people understanding and understanding the mode of action and seeing patient success, et cetera. So I think there's a kind of an underlying kind of uptake and growth. Obviously, we are expecting all physicians want to see more data. And so we're expecting, obviously, that, that would be kind of -- it could provide additional momentum to do that. I personally don't think that the ultimate approval per say would be kind of a major change apart from obviously the label impact. That could obviously be quite significant. But in terms of kind of the way the physicians will be using it in the meanwhile. But I don't know, Andy, do you have a different view?

[Andrew Udell, executive]

Yes. No, I think pretty much all the factors that you say go into things over the year and uptake, meaning they're going to certainly get increased comfort, Part B would be certainly another catalyst, but I think it's just time that we'll take care of increased growth with increased successes. You asked about market access and the difference between the different channels. So just to be clear, there's 2 things. Number one, as far as coverage is concerned, over 90% of U.S. lives. So the coverage is great for even the government subsidizes as well as commercial patients. So that's all U.S. laws. And then when you look at our specific book of business, where the patients come from when you're looking at IgA nephropathy, that's when I discuss around 70% or almost 75%, if you want to look at, that's private insurance and cash-paying patients versus the government subsidized. Does that make sense?

[Rami Katkhuda, analyst]

And I guess with prior ops, it's pretty much the same.

[Andrew Udell, executive]

 Yes, there's similar types of coverage. It's -- as you would anticipate, a specialty product being covered and that's how it's been across both commercial as well as government subsidized.

[Operator]

The next question comes from Erik Hultgård from Carnegie.

[Erik Hultgård, analyst]

I have 2, if I may. First, some of your peers or competitors are considering doing studies -- combination studies with SGLT2s. I was just wondering from a mechanistical point of view and also return on investment point of view, is that something you're planning? And does it make sense? And then just a quick follow-up on previous question on price hike. The list price increase in late January, do you expect that to sort of fall down to the net price line as well?

[Renée Aguiar-Lucander, executive]

 So I guess I'll have Richard give his view on this as well. I guess in terms of the SGLT2s, this is very complement. I mean, we are a locally targeted medication. We're not kind of really focused on the systemic distribution of the drug. So -- and we know obviously today that there are quite a few patients who are on SGLT2 today and also on Tarpeyo talk to physicians, I think a lot of all the physicians that I personally have been in contact with anyone talked to would consider this to be highly complementary. I mean SDLT2 are -- obviously, they're approved in CKD, not specifically Ng. I don't think people look at them as being kind of disease-modifying or anything like that. I think -- but I think they're very safe, and I think they do obviously provide some cardiovascular protection, general cardio protection, et cetera. So do we do already see that being used in quite a lot of kind of patients already with Tarpeyo -- and as I said, it seems to be kind of a positive view from the nephrologist perspective. But I don't know, Richard, if you have anything to add?

[Richard Philipson, executive]

Yes. I mean I think we have an active internal program looking at potential studies that we can undertake to develop franchise for Nefecon. And certainly, we're interested in other treatments that are available. I completely agree with Renee's comments. There's absolutely no reason why Nefecon can't be given on top of an SGLT2 inhibitor. The mechanisms of action are completely different, but they're complementary. So I think it's something that we're actively watching and considering...

[Andrew Udell, executive]

And as far as the price increase and its impact, I'm not sure I completely understand the question. But I mean, in general, the patient out-of-pocket costs are typically a percentage if it's coinsurance or it's a set amount. And we have 0 out-of-pocket costs for commercially covered patients, and no patient will ever not receive our medication due to affordability. So it's not going to have an impact on patient out of pockets really from that aspect.

[Erik Hultgård, analyst]

Sorry, it was more related to the sort of gross versus net price. So the 6.8% price hike, do you expect a similar increase in net price? Or are there higher reset coming in...

[Andrew Udell, executive]

 Yes. No, no. We don't contract with payers, number one, -- so it won't have, but it should have a similar -- we're not going to see a change in any noticeable or anything change from gross to net that you should use in the calculations.ÂÂ

[Operator]

The next question comes from Sebastian Van Scout from BLK.

[Sebastian Van Scout, analyst]

This is Sebastian dropping in for Suzanne today. Congrats on the progress. A couple of questions from our side. For the Phase III Part B readout for the EGFR result, assuming that you will meet the primary endpoint with statistical significance. Some conversations you have with physicians and KOLs, what is the difference from EGFR that would be considered to be the minimum bar and clinically meaningful? And what would you consider to be a strong EFR results? And then I have a follow-up question.

[Renée Aguiar-Lucander, executive]

Well, I'll take a crack at that and Richard, you can complement that. I mean, I think that my view is actually talking to a veriety of physicians that there isn't a specific number or a minimum bar that they would be looking at. I think it is more about kind of actually what can you see in terms of what's the difference in eGFR kind of development in the placebo versus the active arm. But I don't know, Richard, if you have a different experience in your interactions with KOLs.

[Richard Philipson, executive]

I mean no I broadly agree with that. It's not like the external KOLs, experts have some magic number in there, head that says this is the EGFR that you have to achieve below is not good above is good. And I think it's about -- clearly, we need to meet our primary endpoint for the study. And there's also a number of different important secondary endpoints and supportive data. I think we need to take a holistic look at the information that we get from the outcomes of Part B and look at all of that information. So I don't think you can simply say this is the number that we have to achieve.

[Sebastian Van Scout, analyst]

Okay. Got it. But then can you maybe elaborate on the statistics for what difference is the trial powered on eGFR.

[Richard Philipson, executive]

Well, I mean, we don't typically comment on the sort of the detailed statistics of the clinical trial, to be honest.

[Sebastian Van Scout, analyst]

Okay. Got it. And then the final question is on the Alport trial. I was just wondering what the biological rationale and the preclinical data is that supports testing [Indiscernible] in the renal space?

[Renée Aguiar-Lucander, executive]

Richard, do you want to take that?

[Richard Philipson, executive]

 Yes, sure. So I'll try and answer it reasonably briefly in summary. Alport's disease is a rare hereditary genetic disease. There's a clear genetic defect in Alport syndrome. It's a disease of collagen and patients with all ports disease developers. -- progressive renal failure relating to glomerulonephropathy where a significant component of that is a podocytopathy and fibrosis. And we know from -- and maybe you've heard from previous presentations, that setanaxib has a very important role in fibrogenesis relating to the -- its effects on Loxenzyes through NOx inhibition and the inhibition of the generation of reactive oxygen species, which are important in activating fibrogenic pathways. So from that point of view, there's a clear underlying rationale and we have supporting preclinical data from a relevant Alport mouse model that does indeed support that hypothesis. So if you like, we now have preclinical data that are sort of biological biochemical and histological outcomes that support that thesis that setanaxib could have beneficial effects in Alport syndrome.

[Operator]

The next question comes from Johan Unnerus from Redeye.

[Johan Unnerus, analyst]

Congratulations on the good quarter. Very interesting releases continued dosing-- and and I guess, eventually, second dosing. Could you remind us regarding the part if we can get any more insight to the need or use of extended dose or second dose?

[Renée Aguiar-Lucander, executive]

 Yes, I'll start and then maybe Richard can complement the in the Part B, obviously, we are not kind of -- we are not redosing as part of the protocol and the Part B. It really is just an initial treatment and then there is a follow-up period which is observational. But as I think I mentioned in the Q3 report, obviously, there is an open-label extension that's available for patients who have concluded the Phase III. So once they've been in the study for 2 years, they have an ability to then enroll into an open-label extension, where all patients will be given active treatment for 9 months. And as I think we've mentioned there, obviously, there is a fairly significant number failures and those are the at over 60% of those are even related to the fact that the patients actually don't qualify due to the fact that they do not have 1 gram of proteinuria, so they are not considered strictly according to Cicada guidelines to be in that kind of higher risk population. But there will obviously be patients who will have enrolled into that open-label extension. So we will be getting additional information from that study, which obviously is also still blinded and ongoing. But once that study, obviously, once we are able to kind of look into that study, that is probably more likely to give us some more information around retreatment, et cetera. But obviously, I'm sure that in the Part B, we will be -- we will see some trends and see some information regarding how proteinuria reduction performs an EGFR, et cetera. So Richard, do you want to complement on that?

[Richard Philipson, executive]

Sure. So just to make sure it's clear how the open-label extension performs. So it's open label in the sense that everyone in the who gets into the open-label extension receive active treatment. -- but is blinded in the sense that investigators and patients don't know what their original randomized treatment was in the pivotal study. So as relays that gives us an opportunity to get some really interesting information at the end of the study, and we expect that study to complete in early 2024. So we expect to be able to see the performance of patients who did previously receive Metacom and then have received a second course in the Oakland label extension compared with patients who received placebo in the original study and then went on to receive their first course of Metacom in the open-label extension. So some very interesting information will come out of that follow-up study.

[Johan Unnerus, analyst]

Excellent. And so this is to be expected in the first half of '24 and thereabout?

[Renée Aguiar-Lucander, executive]

Yes, most likely would...

[Johan Unnerus, analyst]

And even if it's still relatively early days, is there any sort of take from real life in terms of continuing usage is still well the first patients have been on 11 months, so it's still obviously very early days. And the second part of that question can be also if there is a sense of changing characteristics in the patients quite often when a new product is launched, it then be the more sort of severe patients and as time goes and especially feel more comfortable, they may also opt to treat perhaps some less severe patients.

[Renée Aguiar-Lucander, executive]

Andy, do you want to take that?

[Andrew Udell, executive]

Yes. So I think if I heard you correctly, on the length of therapy, those folks that are on in a longer period of time, we're not seeing anything different with those patients. They're tolerating the medication and we're not hearing back anything, anything noteworthy of patients that have been on longer than the 9 months. And then your comment about patient population for the physicians and uptake. I think that naturally, I think when a new product launches, a physician will try something on maybe a more severe patient and then they'll move to more of a comfort zone or additional patients with success that they achieved with the patient population. That's what we were talking about earlier. I think we're starting to get these success story more and more from our fields, reported back to us on patients, and that can only encourage physician prescribing and wanting to treat additional patients.

[Johan Unnerus, analyst]

And then finally, you -- it's clear that market access is great. Wireless is great. Is there any sort of change in unique prescriber characteristics in terms of level of specialists are you seeing more activities on especially closer to the patient? Or is it more larger centers that is more dynamic or is there sort of great interest across the board?

[Andrew Udell, executive]

Yes. I would say there has been a change in that makeup. A lot of times, that's an individual physician adoption comfort level and when you see them and how often that determines their uptake. So over time, we've just seen an increase in new prescribers as you would anticipate. And that's a lot of time left on there based really on their adoption comfort level and their understanding of the product, the clinical information. Some want to see more information than others. So there's really no one answer as far as that's related. I don't think there's any difference in the new prescribers. I will say though, our targeting segmenting and targeting has been pretty accurate as far as who we anticipated would be the higher enrollers of patients. So that seems to be accurate and targeted which is who we call on the most with our sales force.

[Johan Unnerus, analyst]

And mainly, any surprises in the feedback from the sales and marketing team or commercial clinical team.

[Andrew Udell, executive]

 Yes, no real surprises, no. NothingÂÂ

[Operator]

There are no more questions at this time. So I hand the conference back to the speakers for any closing comments.

[Renée Aguiar-Lucander, executive]

Thank you very much for participating in this Q4 call for 2023. We look forward to talking to you again for Q1 of 2023.