Calliditas Therapeutics AB (CALT) 2020 Q4 法說會逐字稿

Ladies and gentlemen welcome to the Calliditas Therapeutics Q4 2020. Today, I'm pleased to present CEO, Renee Lucander; and CFO, Fredrik Johansson.

(Operator Instructions)

Renee, please begin.

Thank you very much, and welcome to Calliditas Q4 2020 report. And if you -- as you're aware, obviously, there is a disclaimer. And so during today's call, we'll be making certain forward-looking statements may include statements among other things about the timing progress of results. Our ongoing Phase III clinical trials for Nefecon, development plan for setanaxib or any other future product candidates, timing, scope, likelihood, domestic, and/or foreign regulatory filings and approvals. Those forward-looking statements are based on current information assumption and expectations, are subject to change. And involve risks and uncertainties that may cause the actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings, mainly the Securities and Exchange Commission, including any quarterly and annual reports we file.

You're cautioned not to take undue reliance on these forward-looking statements which are only made as of today's date. And the company disclaims any obligation to update such statements.

So with that, I would like to take you to Page 3, just to remind those of you who may not be familiar with the company, that we are a late-stage biopharma company. We're focused on novel treatments in orphan indications. Our lead candidate in Nefecon is a proprietary novel investigation treatment for IgAN, which is intended to be disease modifying, and this is because we are targeting the origin of the disease and the disease in question, obviously, is IgA nephropathy. This means that we are not delivering drug to the kidney, but actually to the ilium and the gut in order to really disrupt or interrupt the very beginning of the disease process.

Nefecon, which is our lead candidate. It's the most advanced product candidate, and we are at position to be the very first approved drug for IgA nephropathy, which is very exciting. We have carried out a Phase III trial, and this is obviously what this quarterly report is going to focus on mainly, as we read out a very strong positive data, in November of 2020. And we are planning to file for regulatory approval, both in the U.S. and Europe in Q1 and Q2, respectively.

And we also believe out there's a significant unmet need in this indication, and we believe there's a very significant commercial opportunity available for Nefecon, if it was to be approved. If you turn to Page 4, this really is a design of the Phase III clinical trial. Because as I said, we read out top line data of this trial in November of 2020.

And the design of this study was virtually identical to the Phase IIB, which also met both its primary and secondary endpoints and which was published in the Lancet in 2017. This was a 200 patients in what we would call the Part A.

So this is the basis for efficacy, safety and market approval. It's a global trial in 19 countries and across just under 150 sites. And the trial is looking at dosing of 16 milligrams of Nefecon versus placebo on the background of an optimized and stable RAS blockade, patients were treated once-daily for 9 months after which the primary endpoint of proteinuria was read out.

So if we turn to Page 5, this is a summary of the clinical trial results of the study NefIgArd. And so this is obviously randomized, double-blinded, placebo controlled trial. And what we saw in terms of the primary endpoint was a 31% reduction in the treatment arm versus baseline. And what we also saw in the treatment arm with regards to the secondary endpoint, namely EGFR, was that the treatment with Nefecon stabilized kidney function which in contrast to the placebo arm, where there was a continuous deterioration all of the kidney function in the placebo group, which was about 4 -- just over 4 milliliters per minute over the 9 -- at the 9-month endpoint. And so what we saw is was a very statistically significant, 27%, you could see a reduction Nefecon versus placebo and also statistically significant eGFR stabilization with Nefecon compared to placebo.

So these results were obviously, we were very delighted to receive these results. They are obviously completely confirmatory to the Phase IIb data that we had previously shown. And also, actually, in terms of the reduction versus baseline, and we actually saw slightly even a slightly stronger reduction here of 31% versus 27%, what we saw in the Phase IIB. And obviously, it's the ultimate treatment goal for this disease is obviously to protect the kidney function and to have this result of being able to see no further deterioration in the treatment group we were obviously delighted in order to be able to report that out.

In terms of the -- some other kind of details around the trial, if you look at Page 6, this just really shows you the demographic characteristics of the Phase III versus the Phase II trial. And as you can see, and as we have previously been communicating, obviously, this patient population was slightly sicker. And so this was obviously a consequence of the fact that there were some KDIGO guidelines that were introduced between the beginning of the Phase II and the Phase III which led to a higher kind of inclusion criteria in terms of UPCR for Phase III as well as the fact that we slightly lowered the cut-off of in terms of eGFR from 44 to 35 mls per minute in the Phase III.

If you turn the page -- turn to Page 7, with regards to the safety profile, there were really no surprises. It's generally well tolerated. Basically in keeping with the Phase IIB results. As we all know, budesonide has very poor bioavailability. And therefore, this type of safety profile is what would be expected. So with the most common adverse events were similar to those, which were observed in the Nef-202. There was a lower frequency in reporting of some of these adverse events. And this -- we put down to the fact that, obviously, the Phase IIb design was fairly unusual and in that it had a solicited adverse event supporting both in terms of potential glucocorticoids related and GI-related adverse events.

We also saw similarly adverse -- no adverse clinical effect on-body weight. On blood pressure on HbA1c. And again, this is obviously completely different type of profile compared to that type of profile, which we are familiar with regards to high-dose systemic steroids where there is indeed a significant impact both on the metabolic and cardiovascular system as well as severe infections, et cetera, which we obviously saw none in the Phase III.

Turning to Page 8. Just again, some general more information about the Phase III. This just lays out the discontinuations, both in terms of the study treatment as well as the study of cells. And obviously, these numbers are very low. And so actually, the discontinuation study is about just over 3%. And the total discontinuation of study treatment is 9%, which is a very, very significantly different number than what we saw in the Phase IIB, which, again, our thesis had been for a long time that the design of this study clearly impacted some of those outcomes.

So that really is a little bit about the kind of actual data and readouts and numbers, et cetera, of the Phase III. And what I now want to do just to spend a couple of minutes on what this -- what kind of implications or what this can be translated into potentially using a variety of different frameworks and publications.

So we turn to Page 9. This is something that I'm sure a lot of you will be familiar with. This is the trial-level assessment. So this is the meta-analysis framework, which we collaborated with a variety of universities on. And actually, the original version of this was published by Inker et al in 2016. And it was this framework which the FDA then accepted as a basis for kind of looking at proteinuria as a surrogate endpoint.

The FDA has since obviously continued to work on this and develop this framework. Both in context of NKF, and again working with the various universities and other academics and so this is an updated version. This is actually another publication from 2019, which also includes additional interventional studies in IgA nephropathy. And the head author here is Thompson, this is Aliza Thompson, who's the deputy, the head of the Cardiorenal division.

So with this as a background, this obviously framework looks at the correlations, or the correlation between kind of really looking at the treatment effect of proteinuria and then which translates into a certain hazard ratio on the left. And as you can see, there's a line that runs through this, it actually shows the actual -- the kind of -- the actual kind of line that shows the correlation between a reduction in proteinuria and a reduced risk of ending up in end-stage renal disease.

So with this framework, which is obviously well-known and published in journals, et cetera, and have been discussed at a variety of workshops, which the FDA and EMA, NKF, et cetera, have organized. If we turn the page, what we can do then, and this actually refer -- this is a slide, which we also showed in our recent R&D Day. It's really an illustration of what kind of an impact one could expect if one uses this type of framework that we just talked about in terms of seeing what clinical impact one might expect from a reduction in proteinuria.

And for those of you who listened in or attended the R&D Day, this was actually part of a Professor Barratt's presentation at our day -- at our R&D Day, and there was a similar presentation that he had made at Travere's R&D Day in 2020. And what this really just looks at is to say, depending on the kind of reduction in proteinuria that is seen in a clinical trial. And this assumes that, that is on top of standard of care.

One will get a certain hazard ratio when you put that number into the framework that I just reviewed with you and you read out there from the y-axis what the hazard ratio is. And this looks at the different hazard ratios that one would arrive at various kind of treatment effects. And as per Professor Barratt's Description, obviously, there is some data that is -- comes from the University of Lester, which actually then provides a kind of a framework in terms of progression without intervention. And this would then show -- would basically be the reflection of a hazard ratio of one.

So this would show that approximately 50% of the population would progress and have an event, and in this case, an event is described as a composite endpoint of end-stage renal disease or doubling of serum creatinine. And this would then result in about 50% of those -- that population ending up in end-stage renal disease or having this doubling of serum creatinine composite endpoint approximately over 12 -- at 12 -- in excess of 12 years. This was actually the slide that was discussed by Professor Barratt at the day.

And I'm looking at the difference then with regards to different levels of proteinuria reduction. And obviously, in this framework, one can see what the estimated delay of disease progression then is. And as we also mentioned at the R&D Day, obviously, there is a treatment effect at 9 months versus baseline, as we've just covered, but also, obviously, not all patients had reached 12 months at the time of the database lock.

And so -- but based on the trends of those patients who had reached 12 months we would estimate that, that entire cohort would end up somewhere between 48% and 48% -- 42% and 48% at 12 months, which obviously then would translate into a very significant delay in terms of disease progression, if one uses the model and the framework on the prior page. So this would basically indicate that the treatment effect that we can see and also then in terms of some trend analysis, we would expect to see really would provide somewhere between 15- and 20-year delay with regards to disease progression.

Another very important element of this, obviously, of looking at this. If you turn the page, it's also obviously, the eGFR information from the trial. So this obviously provides a very important additional long-term validation. And what we have here is another publication that we also discussed briefly at the R&D Day, which again, comes out of the work that has been done with Inker and also within KF as well as which is a broader look at kind of CKD, which is also something that the FDA obviously had been part of and these type of publication would say that actually the impact on eGFR at 1 year that is highly predictive of the outcome of eGFR at 2 years.

And so what we can see here in this kind of Inkers, this is the Inker paper that we're referring to in terms of broader CKD analysis, shows that this is a 1-year slope. If the 1-year slope is 1.31 mls per minute at 1 year, then there is an extremely high probability of 97.5% that there will be a delay in the clinical endpoint and this is the same clinical endpoint that I just discussed on the previous page, of ESKD, so end-stage renal disease or in end-stage kidney disease or doubling of serum creatinine.

And obviously, we were delighted and very excited in order to see that in the NefIgArd trial at 9 months, the difference between Nefecon and placebo, obviously, was very significant. It was representing 3.87 Mls per minute. And again, this is something that adds to the robustness of the data set that we obviously are very excited to be able to enter into discussions with regulatory agencies with regards to.

So in terms of conclusions, on Page 12, we believe that there is a robust demonstration of efficacy. Both in terms of reduction in proteinuria, and very importantly, eGFR stabilization, which obviously in this kidney disease is the ultimate treatment goal. It is to protect the kidney and thereby delay any further or prevent or delay any further deterioration in kidney function. Tolerability and safety profile was in line in keeping with the Phase IIB, as we've discussed. And very much what would be expected from an active ingredient that has very, very poor bioavailability. It's also highly consistent between the 2 trials. Obviously, there is a broad patient population that shows extremely similar outcomes across the Phase IIb in Phase III.

So with that, I would like to just spend a couple of minutes talking about the next steps. So obviously, we will submit to the FDA regulatory files for accelerating approval of Nefecon in Q1. And if Priority Review is granted, this would actually position us for potential commercialization in the U.S. in Q4 of this year.

Now we are also on track with regards to the submission to EMA of our regulatory filing, and we will also be requesting accelerated assessment, if that is granted, that could enable us to have an approval as early as Q1 2022.

And I said, we are very much looking forward to our interactions with the regulators based on the robust data package, which we have. We're also continuing, obviously, to build out organization in the U.S. in line with our communicated plans, and we are very excited about the feedback that we are getting from nephrologists through our MSLs following the Phase III data readout.

So with this, we will change our tracks a little bit and talk -- just give you a brief update on the Genkyotex transaction. So to remind you, we [effected] a control transaction of 67.2%, just concluded in November 3, and that was followed by simplified mandatory tender offer, which closed on December 11, resulting in a total ownership in Genkyotex likely to just over 86%. And we will obviously -- we obviously plan to continue to increase our ownership in alignment we originally communicated intentions with regards to this transaction.

In terms of operations, the work is continuing with regards to additional compounds from the platform as well as all the proprietary work with regards to starting our clinical trials in the second half of this year. And that work is all on track and the collaboration is working well.

If you turn the page, this is really also just a reminder in terms of the mode of action of setanaxib, which is the lead candidate here. And there's also been actually a recent forum review article of NADPH Oxidase Inhibition in Fibrotic Pathologies, which actually provides a very interesting overview of the role of NOX enzymes in a variety of fibrotic diseases.

And as you can see on this page, in terms of Page 15, this covers the NOX enzymes impact across both lung, liver and kidney diseases. And so we are excited about the continued work on setanaxib that we will be carrying out, as I said, towards the latter half of this year. On the next page, just a very brief summary in terms of the clinical activities. Obviously, we have an ongoing Phase III trial. That Phase III trial is fully recruited as of January of this year. So all 360 patients have been included and is, therefore, on track to complete early 2023.

We have, as I just mentioned, plans to launch a clinical trial with setanaxib. One would be in (inaudible), pivotal trial in Phase II/III, pivotal trial in PBC, which we would launch second half of this year as well as a proof-of-concept trial which we also plan to launch before the end of the year in oncology, more specifically in head and neck cancer in conjunction with immunotherapies.

And there are obviously 2 investigator-led studies, which are still ongoing, 1 in DKD and 1 in IPF. And the IPF study has started recruitment, as you may remember, in Q4 of 2020. And obviously, we also have started our open-label extension of NefIgArd. We have several patients who've enrolled, and we have dosed the first patient in early February. And we would expect a high level of interest from patients based on what we see to roll over into the open-label extension after their completion of the Phase III trial.

We're also planning to start the NefXtend trial this year, which will be more continuous dosing, longer-term dosing using Nefecon.

So with that, in terms of any post period events, obviously, there was the readout of the Genkyotex Phase I study, which provided a pathway really for these trials, which I've just covered. And we also, as I mentioned, completed the enrollment as well as the first patient in open-label extension.

So with that, I would like to hand over to Fredrik to take us through the financials.

Thank you, Renee, and good afternoon, everyone. I will present to you the financial overview for the full year of 2020, and all numbers presented to you are in million SEK as usual. To start with, we reported limited revenues in the period of SEK 0.9 million due to the delivery of Nefecon to China for the use in the Chinese arm of the NefIgArd study as part of the license agreement with the partner, Everest Medicines.

Our total operating expenses for the period amounted to SEK 380.6 million compared to SEK 212.8 million for the same period last year. And out of the total operating expenses, the cost for research and development increased by SEK 91.6 million to SEK 241.4 million compared to 149.8 million for the same period previous year.

And the increase in R&D expenses originates from the increased clinical activities in the NefIgArd trial, as we read out Part A and almost fully recruited, the remaining 160 patients during 2020. But also due to large efforts in the cooperation in the clinical, regulatory and product development organizations as we are preparing for the regulatory submissions to the FDA in Q1 this year. And during the second half of 2020, we also started preparations for the Nefecon add-on trials, where we dosed the first patient in the open-label extension in the beginning of this year, as Renee just mentioned.

The sales and administration costs amounted to SEK 141.7 million for the period to be compared with SEK 62.9 million for the same period last year. The increase of SEK 78.8 million between the periods is primarily related to the increased activity and headcount increase in the organization generally, including the increased cost for pre-commercial activities in the U.S. as we grow in all areas and preparing for the potential commercialization in the U.S.

Some activities we performed during the year was [NASDAQ] in U.S. and acquisition Genkyotex, as the most prominent ones, and these have also contributed to the increase in the administration costs. This leaves us with an operating loss of SEK 379.7 million for this period compared to an operating loss of SEK 28 million for 2019.

But remember, we had a SEK 184.8 million in revenue included in the P&P from China in 2019. The cash flow used in operating activities for the period amounted to SEK 309.2 million compared to SEK 71 million for the previous year. The increase in the operating cash flow used for this period is mainly relative to the increase in operating expenses. And for '19, as Renee said, we had a $15 million upfront payment received from Everest.

Our net cash effect from our investment and financing activities combined was SEK 596 million, and this is mainly due to the U.S. IPO on NASDAQ in June, where we've raised a gross amount of SEK 891.4 million, less the net cash effect of SEK 254.8 million used in the Genkyotex transaction.

And part of our U.S. IPO proceeds, have remained in U.S. dollar positions to ensure we control our cash reach since the buildup of our U.S. operations means cost in U.S. dollar.

And having a balance sheet with SEK as accounting currency and with the weakening USD to SEK ratio, we saw in the period financial expenses of SEK 56.4 million due to unrealized foreign currency losses on cash accounts. Our cash position remains very solid as we had a cash position of SEK 996.3 million at the end of December. This was all from me. And now back to you Renee.

Thank you very much. And so with this, I'd be happy to hand over to the operator to take any questions from anyone on the line.

(Operator Instructions)

Our first question comes from the line of Maury Raycroft from Jefferies.

Maury?

Maury, your line is unmute. Can you please unmute yourself? We will try the next question from Annabel Samimy from Stifel.

And thank you also for laying out the eGFR predictive capacity on the study over there, it was very interesting. I was just curious on that. Did FDA require for you to have met that eGFR secondary to be able to file, or is that a nice to have? I guess, in other words, does that make your filing that much more robust since you admit that eGFR stability of a secondary endpoint? So that's my first question. And then I have some follow-ups.

Okay. So obviously, the -- there's a couple of answers to this. Obviously, the primary endpoint is reduction of proteinuria. This is a supportive secondary endpoints. And so just to -- but on the other hand, obviously, it is an orphan disease. And I think the agency has always been very clear about the fact they would like to look at the totality of the data. So obviously, eGFR is a very component -- a very important component of what they're looking at as they're trying to assess the data package in its totality and eGFR, the fact that we've seen such a robust impact on eGFR obviously provides, I guess, in my view, certainly adds significantly to the robustness of the data package that we can provide to the regulators.

Okay. Great. And then just on the different types of studies that you're conducting right now, you obviously have a Part B study that's fully -- Part B of the study that's fully enrolled, and then you just started dosing the OLE study. And it seems like both of them are enrolling patients from Part A. Are we going to see data from the OLE study? And can any of that data potentially derail the part B or this -- the analysis of Part B? Are they including the same patients? Is it separate patients from Part A?

I guess I'm just trying to understand as you continue those 2 studies? And when we might see readout of the OLE study?

Sure. So in order to qualify for inclusion in the open-label extension, you must already have completed 2 years of treatment in NefIgArd. So basically, anybody -- so the actual -- all patients are already recruited into Part B. And so obviously, you wouldn't be qualified to enter into the open-label extension until you've completed the NefIgArd study. So it is, for definition, the same patients. It's just a timing issue. You have to go through the treatment first before you go into the open-label extension.

I see. And are we going to -- since it's open-label, are we going to see any data emerging from that before we see the outcome of the Part B study?

So I mean I guess that most -- I guess, my view would be kind of most likely not any significant data because, obviously, it is an open trial. So obviously, we have different opportunity to report data out on that versus a blinded trial. But in order to, obviously, what we're looking at here is also looking at kind of retreatment versus naive patients who've had to be on placebo. And so I think in order for us to get to kind of a relevant data set, we would need to have a fair amount of patients included in that and also, they would obviously then have to have gone through their kind of 9 months of treatment. So it wouldn't be my expectation that there would be any kind of significant announcements around the open-label extension until there is a completion of the -- or very close to a completion, I guess, of the Part B.

Okay. And if I may, one more question. I just want to know the difference between the discontinuations that you showed, you had up 5.1% related to AEs, but then you have the full analysis set of 3.5%. Can you just explain to me the difference between the 5.1% and the 3.5%? What is the full analysis that you're talking about here?

Sure. Yes. I'll ask Richard Philipson and our Chief Medical Officer, to take that question.

Sure. So Part A full analysis set was the analysis that used for the primary analysis, that's the 199 patients included in Part A. So if we look at that population overall, 19 patients withdrew from treatment, but they still remain in the study or have the potential to remain in the study. So they're not completely removed from the study. And of those 19, 10 or 5.1% of the overall full analysis set 10 discontinued due to AEs.

And we'll try Maury Raycroft again, from Jefferies.

Sorry, would you -- can you have him muted, go ahead. Yes, go ahead Maury.

Congrats on the progress. I was going to ask on -- so with some of the baseline characteristics that you've reported, you've broken out the patients who are less than 2 grams, greater than 3.5 grams than the patients in between there and so for the -- your patients at baseline with proteinuria greater than 3.5 grams. Can you talk more about the magnitude of proteinuria reduction you're seeing there?

I guess, is the 31% mean reduction consistent for the 3 groups? Or can you talk more about the range that you're seeing?

So I guess that our view is really that we don't provide any additional kind of detail on this simply because we do still have a trial that's blinded and ongoing. But I will for good order, also hand over to Richard, our CMO just to confirm.

Yes. I mean, I was going to say something similar. I mean, that's essentially getting into substantial amount of detail relating to subgroup analysis. So we're not releasing those kind of subgroup analysis in detail because, as Renee said, this is an ongoing blinded study.

Understood. And then just as another follow-up on the open-label extension data. So I think at your R&D Day, you talked about potential for repeat dosing and extended dosing and so I'm wondering if you're going to include some of the data from those studies in your FDA submission for review and -- or for label discussions?

So obviously, we're filing with the FDA this quarter. And so the open-label extension has obviously just started because the first patient who was eligible to roll over. If you think about our first patient into this study was November 2018. And so obviously, the first patient was eligible after a 2-year period to roll over into the open-label extension was really kind of in kind of November, December time frame last year. So any kind of data from these -- from the open-label extension will probably be much further down the line, then what will then basically the review period.

Got it. So that would probably be used for the confirmatory data that expands the label then.

Yes. These trials are more just for kind of [healthy economic] purposes and to kind of guide actual clinical practice.

And the next question comes from the line of Yigal Nochomovitz from Citi.

I had 2, Renee, on the commercial uptake for Nefecon first, with regard to feedback from payers, what is your expectation around Nefecon requiring a prior authorization? Is that the expectation that the patient will have to have failed the RAS or steroids in order for payers to cover Nefecon?

And then secondly, what is your expectation with respect to the frequency of therapy in the commercial setting where patients, or are you expecting the physicians will treat beyond the 9-month period, meaning continuous treatment? Or will this be sort of an episodic treatment where they're on for 9 months and then they're off for a period of time and then they resume therapy again?

Okay. So what we did -- IQVIA did a fairly substantial kind of market landscape research work on our behalf. And so they did in that kind of research they did do kind of try to address both of these points that you're raising. So from a payer perspective, there was a large kind of payer research that was conducted. I think it was covering about 225 million lives in the U.S. And there in terms -- from a payer perspective, obviously, this is an orphan disease that has previously never had anything approved.

So the payers are not kind of really used to getting this coming across their desk. But they were obviously shown the Phase IIb profile in that market research. And on that basis, what we found about was that in that kind of range, the range we've been kind of talking about before, which was a spontaneous range from their perspective, $55,000 to $85,000 per treatment at period of 9 months.

They basically said that they would -- and in our view, I think we've treated appropriately, so they would expect it to be the prescription to be done by specialists. And all of these patients really do end up with a nephrologist. They would expect it to have -- that there would be a diagnosis that was valid in terms of the actual disease.

And a couple of them did mention that they would look to step edit in terms of ACEs and ARBs. So that's really kind of what came out of that kind of market research that we saw. And obviously, in terms if you look at guidelines that is the only kind of recommendation that the guidelines have is to actually treat these patients with ACEs and ARBs.

And I think that as in most CKD indications, these patients are already on blood pressure lowing agents there's ACEs and ARBs, then there's combinations, and they are kind of optimized and titrated with a variety of these kind of ACEs and ARBs to kind of get to as good of a position as they can. But obviously, as we know, that doesn't really address kind of the underlying progression, which we see in a lot of these patients.

But this is obviously something that we already do -- we've already done our trial on top of optimized ACEs and ARBs. So from our perspective, we would expect that blood pressure lowering agents will continue to be used in CKD indications, including IgA nephropathy. So we don't really see that as an issue, I must say because I think pretty much all patients are already on -- and that's what we found also kind of actually in our Phase IIb trial.

So that's really what we found out from that. I think in terms of the treatment paradigm, I would say that the physicians in that market research kind of fell into 2 buckets really. One group of physicians felt like they actually appreciated the ability to be able to treat patients intermittently. So actually put patients on a 9-month treatment cycle, and then they see these patients 3 or 4 times a year anyway, and they would follow them in terms of both eGFR and proteinuria and if they felt that the disease was kind of taking hold again or that progression was starting again that they would put them on another treatment cycle.

Whilst there was another group of nephrologists who clearly felt that as long as they're patient we're seeing a benefit from the medication and could tolerate it, then actually, they would just prefer to keep the patient on the medication.

So I think that there are 2 kind of different approaches, I guess, is what we found from the market research. But that's also obviously why we are going to -- on the basis of the Part B, we will obviously get a lot of information with regards to the longer-term impact of this treatment. And as we've already indicated, for example, is that on the that there is a continued benefit and significant continued decline in proteinuria, for example, over the first 3 months. And this will give us a much longer time period to kind of be able to know that better than what we do today, and that data is just data that we don't have today.

And I think that from that perspective, this will also, obviously, something that we're doing, both in NefXtend and open-label extension, is to provide more -- really more information and background to these treating nephrologists with regards to both of those approaches, both the retreatment as well as the extended dosing.

That's very helpful. And then just one question on other indications for Nefecon. I think you had mentioned in the past, autoimmune hepatitis what's the status of that planning? And are there other indications for Nefecon that you're targeting?

Yes. So we've had in last year, we did have interactions with the FDA with regards to autoimmune hepatitis, and we believe that we have we've had very, very good guidance. And I think we're very close to what we believe is kind of a clear regulatory path forward, which would really involve a late-stage clinical trial AIH. There are a couple of other things -- a couple of more things we'd like to kind of go back and get some further clarity on, but we would expect later this year to have -- to kind of have final clarity on the way forward in AIH.

And that obviously would kind of rely on the same type of kind of basis and being able to provide just a drug that is more appropriate for kind of chronic treatment than systemic steroids, simply due to the big difference in safety profile and particularly in something of a chronic treatment like AIH. They're obviously compliance and remission issues, on the basis of what's available today as there's nothing approved. So that's really where we stand in terms of AIH.

We have also, obviously, previously also discussed PBC. And we are continuing. Actually, we also have dialogues around PBC, and we're continuing those dialogues in parallel. But in terms of a clinical trial, the first clinical trial that we will conduct is with setanaxib in the pivotal Phase II/III trial that we are planning to start this year.

And we have one more question from the line of Rami Katkhuda from LifeSci Capital,.

Just a quick one for me. But based on Genkyotex' discussions with FDA, do you still plan to use GGT as a primary endpoint for the upcoming PBC trial? Will you focus on ALP instead?

No. Since this would be a registrational -- potentially registrational trial. We would seek to use the validated endpoint, if you like, which in PBC is ALP.

And as there are no further questions, I'll hand it back for closing remarks.

Great. Well, thank you very much for taking the time to listen to our Q4 report, and we look forward to talking to you again in 3 months' time and give you an update as to both our regulatory progress as well as our commercialization efforts in the U.S. Thank you.

This concludes our conference call. Thank you all for attending. You may now disconnect your lines.