Q4 2020 Calliditas Therapeutics AB Earnings Call
something disclaims any obligation to update such statements
Renee Aguiar: Thank you very much and welcome to Calliditas' Q4 2020 report. As you know, obviously, there's a disclaimer, and so during today's call, we'll be making certain forward-looking statements, which may include statements among other things about the timing, progress, and results of ongoing phase 3 clinical trials for Nefacon, development plans for Cetanaxib, or any other future product candidates, timing, scope, likelihood Those forward-looking statements are based on current information, assumptions, and expectations, which are subject to change, and involve risks and uncertainties that may cause actual results to differ materially from those contained in the forward-looking statements.
So with that I would like to take you to page three just to remind those of you who may not be familiar with the company that we are late stage by a former company were focused on novel treatments an orphan indications are lead candidate mexicon is a proprietor and level investigation treatment Dragon 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 page him in the gut, uh, in order to really disrupt or interrupt the very beginning of the disease process leprechaun, which is our lead candidate is the most advanced product candidate and we are at position to be the very first approved drug, uh for IGA nephropathy, which is very exciting. We have carried out.
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Three trial and this is obviously what this quarter report is going to focus on mainly as we read out very strong and positive data in November of 2012 and we are planning to file for regulatory approval both in the US and Europe in q1 and Q2 respectively and we also do hope there's a significant element need into syndication and we believe that there's a very significant commercial opportunity available for Network on if it goes to be approved if you turn to page for this really is a design of the phase 3 clinical trial because as I said, we read out top-line data of this of this trial in November of 2018, the design of this study was virtually identical to the face to be which also meant both its primary and secondary endpoints wage.
Renee Aguiar: So with that, I would like to take you to page three. Just to remind those of you who may not be familiar with the company, we are a late-stage biopharmaceutical company. We're focused on novel treatments in orphan indications. Our lead candidate, Nefacon, is a proprietary novel investigation treatment for IgN, 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.
Renee Aguiar: This means that we are not delivering the drug to the kidney but actually to the ileum in the gut, in order to really disrupt or interrupt the very beginning of the disease process. Nefacon, which is our lead candidate, is the most advanced product candidate, and we are positioned to be the very first approved drug for IGA nephropathy, which is very exciting. We have carried out a phase 3 trial, and this is obviously what this quarterly report is going to focus on mainly, as we read out very strong and positive data in November of 2020.
Which was published in the Lancet?
2017 this was a 200 patients in what we would call the part A. So this is the basis for efficacy safety and and Market approval. It's a global while in nineteen countries and across just under a hundred fifty sites. And the trial is looking at dose of 16 mg of an African versus placebo on the backgrounds of an optimized unstable raspa paid patients were treated once-daily for nine months after which the primary endpoint approaching area was dead out. So if we turn to page five, this is a summary of the clinical trial results of the study method guard. And so this is obviously randomized double-blind placebo-controlled trials and uh, what we saw in terms of primary endpoint was a 31% reduction in the treatment arm versus baseball.
Renee Aguiar: 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 that there is a significant need for this syndication, and we believe that there is a very significant commercial opportunity available for an effort if it were to be approved.
Renee Aguiar: If you turn to page 4, this really is the design of the Phase 3 clinical trial. As I said, we will read out the top-line data from this trial in November of 2020. 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 200 patients in what we would call 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 will be also start in the treatment on with regards to the secondary endpoint name of the egfr with the treatment with method on stabilized kidney function wage, which in contrast to the placebo arm where there was a continuous deteriorate configuration of the kidney function in the placebo group, which was about 4 a.m. Just over four milliliters per minute over the nine at the nine-month and point. And so what we saw was a very statistically statistically significant 27% you pursue our reduction Network on versus placebo and also statistically significant energy for stabilization with an African compared to Placebo. So these results were obviously we were very delighted to receive these results. They are, you know, obviously completely confirmatory the fees to Thursday.
Renee Aguiar: The trial was looking at dosing of 16 milligrams of nefacon versus placebo on the background of an optimized and stable RAS pathway. Patients were treated once daily for nine months, after which the primary endpoint of proteinuria was read out. So if we turn to page five, this is a summary of the clinical trial results of the study Nesigard. And so, this is obviously a 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.
Data that we had previously shown and also actually in terms of the reduction versus Baseline and we actually saw a slightly even a slightly stronger reduction here 30% versus 27% will be so in the face to be and obviously, you know, it's a you know, the, you know, the ultimate treatment go for this disease 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 be able to report that out.
Renee Aguiar: And what we also saw in the treatment arm with regard to the secondary endpoint, namely EGFR, was that the treatment with Nefacon stabilized kidney function, which is in contrast to the placebo arm, where there was a continuous deterioration of kidney function in the placebo group, which was just over 4 milliliters per minute at the 9-month endpoint. And so what we saw, this was a very statistically significant 27% UPCR reduction with nephrocon versus placebo and also statistically significant EGFR stabilization with nephrocon compared to placebo. So, these results, obviously, We were very delighted to receive these results.
In terms of the some other kind of details around the trial and if you look at page six, this just really shows you the demographic characteristics of the phase 3 versus The Phase 2 trial and as you can see and as we have previously been communicating obviously this patient population off slightly sicker. And so this was obviously a consequence of the fact that there was some codigo guidelines that were introduced between the beginning of the phase two and phase three which led to a higher wage. Um, kind of inclusion criteria in terms of uh, UPC are for phase three as well as the fact that we slightly lower the cut off in terms of egfr from 45 to 30 GB per minute in the face 3, if you turn the page to to turn to page seven with regards to the safety profile wage.
Renee Aguiar: They are, you know, obviously completely confirmatory of the Phase IIb data that we had previously shown. And also, actually, in terms of the reduction versus baseline, we actually saw a slightly, even a slightly stronger reduction here, 31% versus 27%, which is what we saw in Phase IIb. The ultimate treatment goal for this disease is obviously to protect 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.
They were really no.
Renee Aguiar: In terms of 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 3 trial versus the phase 2 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 Cadigal guidelines that were introduced between the beginning of phase 2 and phase 3, which led to a higher kind of inclusion criteria in terms of UPCR for phase 3, as well as the fact that we slightly lowered the cutoff in terms of EGFR from 45 to 35 mls If you turn to page 7, with regard to the safety profile, there were really no surprises.
Prices it's generally well-tolerated basically in keeping with the face to be results as we all know odesza. My dad has very poor bioavailability down there for this type of safety profile is what would be expected and so the most common Adverse Events were similar to those which were observed in an F 202
there was a lower frequency and reporting of some of these Adverse Events and this we put down to the fact that obviously the face to be designed was fairly unusual in that it's had a solicited adverse event reporting both in terms of potential glucosteroid related and GI related Adverse Events wage. We also saw a similarly no adverse no adverse clinical effects 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 with regards to hide do systemic steroids where there is indeed, you know, a significant change both of them at the bar like and cardiovascular system as well as severe infections etcetera, which we obviously saw none in the phase three dead.
Renee Aguiar: It's generally well-tolerated, basically in keeping with the Phase IIb results. As we all know, bedecinide has very poor bioavailability, and therefore this type of safety profile is what would be expected. And so the most common adverse events were similar to those which were observed in the NEF-202. However, 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 2b design was fairly unusual in that it had solicited adverse event reporting both in terms of potentially glucocosteroid-related and GI-related adverse events.
Turning to page eight just to get some general more information about the phase three. This just lays out the discontinuation both in terms of the study treatment as well as the study itself. And obviously these numbers are very low and so actually the the discontinued to Thursdays about just over 3% and the total discontinuation study treatment is 9% which is a very very significantly different number than what we saw in the face to be which again our thesis had been for a long time that the design of the study clearly impacted some of those outcomes.
Renee Aguiar: We also saw, similarly, no adverse clinical effect on body weight, blood pressure, or HbA1c. And again, this is obviously a completely different type of profile compared to that type of profile which we are familiar with with regard to high-dose systemic steroids, where there is indeed a significant impact on the metabolic and cardiovascular system, as well as severe infections, etc., of which we obviously saw none in Phase 3. Turning to page 8, just again, some general more information about phase 3.
So that really is a little bit about the kind of actual data and read outs and numbers Etc the phase three and what I want to do just a, it's been a couple of minutes on what this what kind of implications or what this can be translated into a potentially using a variety of different Frameworks and publications.
Renee Aguiar: This just lays out the discontinuations both in terms of the study treatment as well as the study itself. And obviously, these numbers are very low, and so actually, the discontinuation study is about just over 3 percent, and the total discontinuation study treatment is 9 percent, which is a very, very significantly different number than what we saw in phase 2b, which again, our thesis had been for a long time that the design of the study clearly impacted some of those outcomes.
They return to page nine. 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 on which we collaborated with a variety of universities on and actually the original version of this was published by anchor at all in 26 team and it was this framework which the FDA then accepted as a basis for kind of looking at protein or as a surrogate endpoint.
yesterday has been
Renee Aguiar: So that really is a little bit about the kind of actual data and readouts and numbers, etc., of phase 3. And what I now want to do is spend a couple of minutes on what kind of implications or what this can potentially be translated into 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.
Obviously continue to work on this and develop this framework both in context of an TF and again working with the various universities and other academics. And so this is an updated version. This is actually an another publication from 2019, which also includes additional Interventional studies in IGA nephropathy.
The head author here is Thompson says Alicia Thompson who's the deputy head of the cardio-renal division?
Renee Aguiar: 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 the context of NKF and again working with 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 Thomson, so this is Alicia Thomson who is the Deputy Head of the Cardiorenal Division.
So with this is the background this obviously framework looks at the correlation. So the yeah the correlation between kind of really looking at the treatment effect of protein area off and then which translates into certain Hazard ratio on the left. And as you can see there's a line that runs through this that actually shows the actual kind of our actual kind of line that shows the correlation between the reduction and protein or and 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 a variety of workshops, which the FDA and EMA and Chaos etcetera organized. Uh, if you turn the page what we can do then and this actually refer this is a slide which we also showed in our recent are indeed a month. 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 in fact one might expect from a reduction in protein area. And for those of you who listened in or attended the R&D day, this was actually part of a professor it's presentation at our day at R&D day and there was a similar presentation that he had made at Revere's are indeed a in 2020 off.
Renee Aguiar: So with this as a background, this obviously framework looks at the correlation, so 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 that actually shows 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.
And what is really just looks at is to say depending on on the kind of reduction in protein area that is seen in a clinical trial and this is Sue's that that is on a standard of care when 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 wage and this looks at the different Hazard ratios, the one with arrive at various kind of treatment effect and as Professor Barrett's description, obviously, they use some data that is comes from the University of Leicester, which actually then provides a kind of a framework in terms of progression without intervention wage. And this would then show would basically be the reflection of a hazard ratio of one. So this would show that you know, approximately fifty percent of the population would progress
Renee Aguiar: 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, NKS, et cetera, have organized. If we turn the page, what we can do then, and 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 Barrett's presentation at our R&D day, and there was a similar presentation that he had made at Trevor's R&D day in 2020.
I'm having an event and in this case an event is described as a composite endpoint.
Renee Aguiar: 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 at various kinds of treatment effects.
In stage renal disease or doubling of serum creatinine and this would then result in about 50% of those, uh that population ending up in end-stage renal disease or having this doubling of crap mean to impose it on point approximately over twelve at 12 in excess of twelve years. This was actually the slide that was discussed by Professor Barrett at the day off looking at the difference. Then with the guards two different levels of protein are in a reduction.
Renee Aguiar: And as per Professor Barrett's description, obviously, there is some data that comes from the University of Leicester, which actually then provides a kind of framework in terms of progression without intervention. And this would then show, would basically be the reflection of a hazard ratio of 1.
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 a month versus Baseline as we've just covered but also obviously not all patients had reached 12 months at the time of the database law 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 $40.46 forty to 48% at twelve months which obviously them would translate into a very significant delay in terms of disease progression. If one uses them in the framework on the prior page, so this would basically indicate that you know, eight the treatment effect that we can see and also dead
Renee Aguiar: 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 serine creatinine. And this would then result in about 50% of that population ending up in end-stage renal disease or having this doubling of serine creatinine composite endpoint, approximately, in excess of 12 years. This was actually the slide that was discussed by Professor Barrett that day.
Renee Aguiar: And looking at the difference then with regard 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 nine 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 percent, 42 and 48 percent 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.
And in terms of some Trend analysis, we would expect to see really would provide somewhere between fifteen and twenty years delay with regards to disease progression.
Another very important element of this. Obviously. I'm looking at this if you turn the page is also obviously the egfr off information from The Trial. So there's obviously provides a very important additional long-term validation and what we have here is just another publication that we also um, uh discuss briefly at the R&D day which again comes out of the work that has been done with anchor and also a 10 k f as well as which is a broader look at kind of CKD, which is also something that the FDA, you know obviously had been part of money and these type of publication would say that actually the impact on E G afford one year is highly predictive of the outcome of easier for it to you.
Renee Aguiar: So, this would basically indicate that, you know, the treatment effect that we can see and also, in terms of some trend analysis, we would expect to see really would provide somewhere between 15 and 20 years of delay with regard to disease progression. Another very important element of this, obviously, of looking at this...
And so what we can see here in this kind of inkers is the Anchor Paper that we're referring to in terms of broader ctd analysis shows that the this is a one year slash. The one you're slope is 1.31 per minute 1 year, then there is an extremely high probability of 95.5% that there will be a delay in the back end point. And this is the same clinical and point that I just discussed on the previous page of e s k d. So end stage renal disease are in end-stage kidney disease or doubling of serum creatinine.
Renee Aguiar: If you turn the page, it's also obviously the EGFR information from the trial. So this obviously provides very important additional long-term validation, and what we have here is another publication that we also discussed briefly at R&D Day, which again comes out of the work that has been done with INCRE and also with NKF, as well as a broader look at CKD, which is also something that the FDA, you know, obviously had been part of.
and obviously
See we were delighted. I'm very excited in order to see that in the next nine months of the difference between Africa and Placebo obviously was very significant off this represented 3.7 per minute. And again, this is something that you know, adds to the robustness of the data set that we obviously are very exciting to be able to enter into discussions with regulatory agencies with regards to so in terms of conclusions on page twelve, we believe that there is a robot demonstration of efficacy off both in terms of reduction in protein area and and very importantly Gia for stabilization which obviously in this kidney disease is the ultimate treatment goal. It is to protect Bap kitne and thereby delay any further or prevent or delay any further deterioration and kidney function.
Renee Aguiar: And these types of publications would say that actually the impact on EGFR at one year is highly predictive of the outcome of EGFR at two years. And so what we can see here in this kind of INCURS, this is the INCURS paper that we're referring to in terms of broader CKB analysis, shows that this is a one-year slope.
Renee Aguiar: So if the one-year slope is 1.31 mL per minute at one 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 end-stage kidney disease, or doubling of serum creatinine. And obviously, we were delighted and very excited to see that in the NIFAGARD trial at nine months, the difference between NIFAGARD and placebo, obviously, was very significant, which represented 3.87 mils per minute.
Told her ability and safety profile was in line and keeping with the fees to be as we've discussed and very much what would be expected from an active ingredient that has very very poor by availability. So it's a highly consistent between the two trials. So obviously there is a broad patient population that showed, you know, extremely similar outcomes across the face to be in phase three.
Renee Aguiar: And again, this is something that, you know, adds to the robustness of the data set that we are obviously very excited to be able to enter into discussions with regulatory agencies. 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, GFR stabilization, which is obviously the ultimate treatment goal in this kidney disease. It is to protect the kidney and thereby delay any further or prevent or delay any further deterioration in kidney function.
So with that I would like to just spend a couple of minutes talking about the next steps would be uh, we will submit to the FDA regulatory file for Accelerated approval of Mexican, uh in q1 and if priority review is a granted this would actually position as for potential commercialization in the US and Q4 of this year. We are also on track with regards to the submission to Ema Latorre smiling and we will also be requesting accelerated assessment if that is granted that could could enable us to have an approval as early as q1 2022 month.
Renee Aguiar: Tolerability and safety profile was in line with phase 2b, as we've discussed, and very much what would be expected from an active ingredient that has very, very poor bioavailability. So it's highly consistent between the two trials. Obviously, there is a broad patient population that shows extremely similar outcomes across phase 2b and phase 3. So with that...
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 that organization in the US and in line with our communicated plans, and we are very excited about the feedback that we are getting from an astrologist through RMS else following the phase 3 data Rita.
Renee Aguiar: I would like to just spend a couple of minutes talking about the next steps. So obviously, we will submit to the FDA a regulatory dossier for accelerated approval of methadone 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. We are also on track with regards to the submission to EMA or regulatory filing, and we will also be requesting accelerated assessment, which could enable us to have an approval as early as Q1 2022.
So with this will we will change a little bit and talk just give you a brief update on the entire text transaction. So to remind you we affect the control transaction 7.2% just concluded in November 3rd and that was followed by simplified mandatory tender offer which closed on December eleventh and the resulting in a total ownership wage, uh engine context likely do just over 86% and we will obviously be obviously plan to continue to increase our ownership in alignment. We originally communicated intentions wage for this transaction.
Renee Aguiar: And I said we are very much looking forward to our interaction with the regulators based on the robust data package that we have. We're also continuing, obviously, to build out our organization in the U.S. in line with our communicated plans, and we are very excited about the feedback that we are getting from astrologists through our MSLs following the Phase III data readout. So with this, we will change tack a little bit and talk, just give you a brief update on the Genkiatex transaction.
it's
Terms of operations the work is continuing with regards to you know, additional compounds from the platform as well as all the Preparatory work with regards to starting of clinical trials in second half of this year off that work is all on track and the collaboration is working. Wow, if you turn the page, this is really also just a reminder in terms of the mode of action of sleep and excessive wage, which is the lead candidate here and there's also being actually recent form of the article of nadph oxidase in addition and fibrotic pathologies, which actually provides a very interesting overview of the role of nonsense times and variety of fiber optic diseases. And as you can see on this page in terms of page fifteen, this covers the knock sensor and impact across both lungs liver and kidney diseases and so we are excited about the continued work on set on access that we woke.
Renee Aguiar: So to remind you, we effected a control transaction of 67.2%, which was concluded on November 3rd, and that was followed by a simplified mandatory tender offer, which closed on December 11th, resulting in a total ownership in Genkiatex likely to be just over 86%. And we will obviously, obviously plan to continue to increase our ownership in alignment with the originally communicated intentions with regard to this transaction.
Renee Aguiar: In terms of operations, the work is continuing with regards to additional compounds from the platform as well as all the preparatory work with regards to starting of clinical trials in the second half of this year, and that work is all on track, and the collaboration is working well, turn the page this is really also just a reminder in terms of the mode of action of Cetamaxib which is the lead candidate here and there's also been actually a recent former re-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, In terms of page 15, this covers the knock-sense hand impact across both lung, liver, and kidney diseases. And so we are excited about the continued work on Seton Access 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.
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've had ongoing phase 3 trial that phase 3 trial is fully recruited as of January of this year. So all three hundred sixty patients have been included with uh, and is therefore on track to complete an early 2023. Um, we have as I just mentioned plans to launch a practical trial with such an active one would be infinite adaptive pivotal trial in phase two three pivotal trial in PVC, which we would launch second half of this year off as well as a proof-of-concept trial which we also plan to launch before the end of the year in oncology more specifically and headed Mac head and neck cancer in conjunction with birth.
You know therapies and they're obviously to investigate a list studies which are still on going on in d k d and one in ipf and the ipf study started recruitment as you may remember in Q4 of 2020.
Renee Aguiar: Obviously, we have an ongoing phase 3 trial, and that phase 3 trial was fully recruited as of January of this year. So all 360 patients have been included, and the study is therefore on track to complete early 2023. We have, as I just mentioned, plans to launch a clinical trial with Seton Acid. One would be an adaptive pivotal trial in a Phase II-III pivotal trial in PBC, which we would launch in the 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, specifically in head and neck cancer in conjunction with immunotherapy.
And obviously we also have started our open label extension of Nazi guard. We have several patients who have enrolled and we have those the first page 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 3 trial Thursday. We're also planning to start the next extended trial this year, which will be more continuous dosing longer-term dosing using an ethical.
So with that in terms of any post. Events, obviously there was the readout of the genetics things one study which provided a pathway really for these trials, which I've just covered off 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 Fredrick to take us about the financial. Thank you and good afternoon everyone. I will present to you the financial overview for the full year of 2020 and all numbers presented to you or in life as usual to start with we reported limited revenues in the period of 0.9 million due to the delivery of Mexican to sign up for use in China sort of like a dog study as part of the license agreement with a partner and it was medicine.
Renee Aguiar: And there are obviously two investigative studies which are still ongoing, one in DKD and one in IPF, and the IPF study started recruitment, as you may remember, in Q4 of 2020. And we have also started our open-label extension of NessieGard. We have several patients who've enrolled, and we 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.
Renee Aguiar: We're also planning to start the NEFEC STEM trial this year, which will be more continuous dosing, longer-term dosing using NEFEC. So with that, in terms of any post-period events, obviously, there was the readout of the Genki-Tex Phase I study, which provided the pathway, really, for these trials which I've just covered. And we also, as I mentioned, completed enrollment, as well as the first patient in an open label extent. So with that, I would like to hand over to Fredrik to take us through the financials.
or total operating
Expenses for the. Amount is to 380.6 million compared to 212.8 million for the same period last year and after the total operating expenses the cost for research and development increased by 91.6 million to 241.4 million compared to 149.8 million month free this year and increase in all the expenses originals from The increased clinical activities to the network. Trial that we adopt Forte and almost fully booted the remaining 100,000 patients given twenty twenty but also due to large efforts in the preparation in between the regular and product development organizations, as we are preparing for the Riveter submissions to age twenty-one.
Fredrik Johansson: 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 SEC as usual. To start with, we reported limited revenues in the period of $0.9 million due to the delivery of Naficon to China for use in the Chinese arm of the Nafigard study as part of the license agreement with a partner. Our total operating expenses for the period amounted to $380.6 million compared to $212.8 million for the same period last year.
During the second half of 2020 also started preparations for the network Aladdin trials were reduced the first patients in the open-label extensions extension in the beginning of this year as wage and just mentioned the sales and administration costs amount to 141.7 million for the. To be compared with 62.9 million for the same period last wage increase of 78.8 million between the periods is primarily related to The increased activity and headcount increase and organization generally including the increase cost money for free commercial activities in the us as we grow in all areas and preparing for the potential commercialization in u.s.
Fredrik Johansson: And out of the total operating expenses, the cost for research and development increased by 91.6 million dollars. 241.4 million compared to 149.8 million for the same period last year. And the increase in R&D expenses originates from the increased clinical activities in the NET-A-GOT trial, as we redacted Part A and almost fully recruited the remaining 100 patients during 2020, but also due to large efforts in the cooperation with clinical regulatory and product development organizations as we are preparing for regulatory submissions to the FDA in Q1 this year. And during the second half of 2020, we also started preparations for the methadone add-on trials where we dosed the first patients in the open-label extension trial at the beginning of this year, as Renee just mentioned.
Some activities we perform during the year was the US and the acquisition of the characters. That's the most prominent ones and these have also contributed to the increase in wage Administration costs. Please leave us with an operating loss of 379.7 million for this period compared to an operating loss of twenty eight million for 2019. But remember we had a one hundred eighty four point eight million in Revenue included in the email from China in 2019. The cash flow used in operating activities for the. Mounted to 309.2 million compared to seventy 1 million for the previous year increase in the operating cash flow used for this. Is mainly related to the increase in operating Staffing and 4:19. So just said had $1000000 upfront payment received from Everest.
Fredrik Johansson: The sales and administration costs amount to $141.7 million for the period, to be compared with $62.9 million for the same period last year. The increase of $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 prepare for the potential commercialization in the U.S. Some activities we performed during the year were the IPO in the U.S. and the acquisition of Gankeritas X, as the most prominent ones, and these have also contributed to the increase in administration costs.
We're next to effect from or investment and financing activities combined was 596 million and this is mainly due to the u s i p o en masse back in June where we raced down across the amount of 891.4 million plus the net cash effect of 254.8 million used in the game character transaction and part of our life precedes have remained in the u.s. Dollar positions to ensure we control or cash which since the build-up of us operations and means cost in u.s. Dollar and having a balanced life with SE Ki s eks accounting currency and with the week and then USD to SEK. We sold a. Financial expenses of fifty six point four million volts on Realize for Moses on cash accounts.
Fredrik Johansson: This leaves us with an operating loss of $379.7 million for this period, compared to an operating loss of $28 million for 2019. But remember, we had $184.8 million in revenue included in the finale from the China deal in 2019. The cash flow used in operating activities for the period amounted to 309.2 million, compared to 71 million for the previous year. The increase in the operating cash flow used for this period is mainly related to the increase in operating expenses.
Okay.
And remains very solid as we had a cash position of 996.3 million at the end of December and this was all from me and now back to you. Thank you very much. And so with this I'll be happy to hand over to the operator to take any questions from anyone on the line.
Fredrik Johansson: And for 19, we, as we just said, we had a 15 million dollar platform payment received from Everest. Our net cash effect from our investment and financing activities combined was $596 million, and this is mainly due to the US IPO on NASDAQ in June, where we raised a gross amount of $891.4 million. That's the net cash effect of $254.8 million used in the GameCaretex 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 build-up of our U.S. operations means costs in U.S. dollars.
Thank you. And if you have a question for the speakers, please press zero one on your telephone keypad now.
Our first question comes from the line of Maury recall from Jefferies, please go ahead.
Right line is on. Can you please unmute yourself?
Fredrik Johansson: And having a balance sheet with SEP, SEK as accounting currency, and with the weakened USD to SEK ratio, we saw financial expenses of $56.4 million due to unrealized foreign currency losses on cash-out. Our cash position remains very solid, as we had a cash position of 996.3 million at the end of December. And that's all from me, and now back to you, Bruno.
We will try the next question from Annabel. Samimy from Steve, please go ahead.
Hi, thanks for taking my questions and thank you also for laying out the egfr predictive capacity of the study over there. It was very young. I was just curious on that. Um did FDA require you for you to have met that egfr secondary to be able to file or was that in my to have I guess in other words, does that make your filing that much more robust since you had met that that egfr stability in the secondary endpoint so that that's my first question and my husband phone no.
Speaker: Thank you very much. And so, with that, I'd be happy to hand over to the operator to take any questions from anyone on the line.
Operator: If you have a question for the speakers, press 01 on your telephone keypad now. Our first question comes from the line of Maurice Raycroft from Jeffries. Please go ahead. Can you please unmute yourself?
Okay, so obviously the sales like a couple of answers to this. Obviously the primary endpoint is reduction of protein area. The this is a supportive secondary endpoint wage. And so so suggest to come but on the other hand, it's an orphan disease and I think the agency is always been very clear about the fact that you know, they would like to look at the totality of the data off. So obviously GFR is you know, a very component very important component of of what they're looking at as they're trying to you know, assess the data package, you know in its totality off and egfr the fact that we've seen such a robust impact on egfr obviously provides, you know, I guess in my view, you know, certain wage significantly through the robustness of the data package that we can provide to The Regulators.
Annabel Eva Samimy: We'll try the next question from Annabel Samimy from Stifel. Please go ahead. Hi, thanks for taking my questions, and thank you also for laying out the EGFR predictive capacity. The study over there was very interesting. I was just curious about that; did FDA require you to have met that EGFR secondary endpoint to be able to file, or was that a nice to have? I guess, in other words, does that make your filing that much more robust since you have met that EGFR stability in the secondary endpoint? So, that's my first question, and I have some follow-ups.
Okay, great. And then just on on the different types of studies that you're connected right now, you obviously have the party started a complete party of study that's fully enrolled and then you just started back in the early study and it seems like both of them are enrolling patients from part. Are are are we going to see data from the study in any of that data off potentially derail the part B or the analysis of heartbeat? Are they including the same patience? Is it separate patients from part A. I guess I'm just trying to understand the difference between the two studies and when we might see read out of the o l e study.
Renee Aguiar: Okay. So obviously, there are a couple of answers to this. Obviously, the primary end point is reduction of proteinuria, but this is a supportive secondary end point. And so just to kind of, but on the other hand, obviously, this is an orphan disease, and I think the agency has always been very clear about the fact that they would like to look at the totality of the data. So obviously, GFR is 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.
Sure, so so in order to qualify.
For inclusion in the open-label extension, you must already have completed two years of treatment in that regard. So basically anybody so so the the actual can all patients are already recruited into Part B. And so obviously you wouldn't be it wouldn't be qualified to enter into the open-label extension until you've completed the national study. So it is for definition. The same patience is just a timing issue. You have to go through the treatment first before you go into the open-label extension.
Annabel Eva Samimy: Okay, great. And then, just on the different types of studies that you're conducting right now, you obviously have Part B of the study that's fully enrolled, and then you just started doing the OLE study, and it seems like both of them are enrolling patients from Part A. Are we gonna see data from the OLE study, and can any of that data be used? potentially derailed in Part B, or 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 the difference between those two studies and when we might see readout of the OLE study.
I see and are we going to send it to open-label? Are we going to see any data emerging from on before we see the outcome of the part B study?
So I mean I guess the most I guess my view would be kind of most likely not any significant data because obviously, you know, it is an open truck. Obviously we have it, you know, we've 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 trying to reach treatment versus six patients who has to be no Placebo. And so I think in order for us to get to you know, kind of a, you know, a relevant data set, you know, we would need to have a fair amount of patience included in the office and also they would obviously then have to have gone through their kind of nine months of treatment. So it wouldn't be my expectation that there would be any any kind of significant announcements around open label extension until there's a completion of the, you know, very close to a completion. I guess of the part B.
Renee Aguiar: Sure. So, in order to qualify for inclusion in the Open Label Extension, you must already have completed two years of treatment with NIFAGARD. So basically, anybody, 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 NIFAGARD study. So it is, by definition, the same patients. It's just a timing issue. You have to go through treatment first before you go into the Open Label Extension.
Annabel Eva Samimy: 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?
Okay, and if I need one more question, I just want to know the difference between the discontinuation that you showed you had 5.1% related to AES, but then you have the full analysis set off. Um of 3.5. Can you just explain to me the difference between the 5.1 or the 3.5? What is the full analysis that that came down here. Richard Phillips on our chief medical officer to tape tape that question. So the part a full analysis set was a it's the same analysis set used for the the primary analysis. That's the hundred ninety-nine patients included in part A. So if we look at that population overall nineteen 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.
Renee Aguiar: So I mean I guess that you know most I guess my view would be kind of most likely not any significant data because obviously you know it is an open trial so obviously we have a you know 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 you know kind of a you know a relevant data set you know 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 nine months of treatment so it wouldn't be my expectation that there would be any any kind of significant announcements around the open label extension until there's the completion of the or you know very close to the completion I guess of the part B.
And of those nineteen ten or 5.1% of the overall full analysis set 10 discontinued due to AIDS.
Annabel Eva Samimy: And if I may, one more question. I just want to know the difference between the discontinuations that you showed. You had 5.1% related to AEs, but then you had 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 set that we're talking about here?
Okay. Okay. Thank you. Great. Thank you.
I'll try I'll try more and write off again. I'll just bring it please. Go ahead. Good morning. Everyone everyone.
Richard Philipson: I'll ask Richard Philipson, our Chief Medical Officer, to take that question.
Yeah, that's on the progress and thanks for taking my questions that I was going to ask on. Uh, so what some of the Baseline characteristics that you've reported you've broken out the patients who are logged into grams greater than 3.5 grams, then the patients in between there. And so for the your patience that Baseline with proteinuria greater than 3.5 grams. Can you talk more about the the mag proteinuria reduction you're seeing there? I guess is that 31% mean reduction consistent for the three groups or can you talk more about the range that you're seeing?
Richard Philipson: Thank you for your questions. Sure, so Part A's full analysis set was the analysis set 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 AED. Thank you. Great
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 an ongoing but I will I will forget order also hand over to Richard just to confirm. Yeah, I mean I could say something similar. I mean that's essentially getting into a potential amount of detail relating to subgroup analyses. Um, so we're not releasing those kind of subgroup analyses in detail because Israeli has said this is an ongoing blinded study off.
Annabel Eva Samimy: Great, thank you.
Maurice Thomas Raycroft: and Maurice Raycroft again from Jesse. Please go ahead. Hi, good morning everyone.
Operator: Sorry, Richard, can you hear me?
Maurice Thomas Raycroft: Good Congratulations on the progress and thanks for taking the time to answer my questions. I was going to ask, so with some of the baseline characteristics that you've reported, you've broken out the patients who are less than 2 grams, and greater than 3.5 grams than the patients in between there, and so for 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 three groups, or can you talk more about the range that you're seeing?
Understood understood and then just as another follow-up on the open-label extension data to I think it's your R&D day 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 submission for review and or four label discussions.
So obviously we're we're filing with the FDA this quarter and so the open leave an 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. So obviously the first patient was eligible after two year period to roll over into the owner of an extension was was really kind of in and kind of November December time frame last year. So any kind of date from these, you know from the open-label extension will probably be you know, much further down the line then we'll then basically the review.
Renee Aguiar: 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. Um, but I will, um, I will, for good order, also hand over to Richard, our CMO, just to confirm.
Richard Philipson: Yeah, I mean, I'm going to say something similar. I mean, that's essentially getting into substantial amounts of detail relating to subgroup analyses. So we're not releasing those kind of subgroup analyses in detail because, as Renee has said, this is an ongoing blind, understood. And then just as another follow-up on the open label extension data, so I think it's your R&D day. You talked about the 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.
Got it. So that would probably be used for the the confirmatory data that expands the label then.
Yes, this is these trials are more just for kind of healthy economic purposes and to kind of guide actual clinical practice.
Under said, okay. Thank you for taking my questions.
Maurice Thomas Raycroft: 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 it, our first patient into this study was in November 2018. So, obviously, the first patient who was eligible after a two-year period to roll over into the open-label extension was really kind of in the November, December timeframe last year. So, any kind of data from the open-label extension will probably be much further down the line than basically the review period.
And the next question comes from the line of your number Thomas from City, please go ahead.
All right. Thank you for taking a question on a commercial account feedback from payers. What is your expectation around off the phone with car requiring a prior authorization? Is this the expectation that the quotation will have to have failed the ACR or steroids in order for repairs to cover Network on and then secondly, what is your expectation with respect to the frequency of therapy in the commercial setting will patient am expecting the positions will treat beyond the nine month. Meaning continuous treatment or will this be sort of a episodic treatment where they're on for nine months and then they're off period of time and then they resumed therapy again.
Renee Aguiar: Got it. So that would probably be used for the confirmatory data that expands the label.
Renee Aguiar: Yes, these trials are more just for kind of health economic purposes and to kind of guide actual clinical practice.
Maurice Thomas Raycroft: Okay. Thank you for taking my question. And the next question comes from the line of Yigal Nochomovitz from Citi. Please go ahead. I thank you for taking the questions.
Okay, so what we did?
We added a fairly substantial kind of Market landscape research work on our behalf. And so they did in that kind of research. They did. I do kind of try to address both of these points that you were raising. So from a payer perspective there was a large kind of payer research that was conducted. I think it was covering about 225,000 lives in the US and they're in terms of 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 be getting this coming across their desk, but they were obviously showing the face to be profile in that market research and on that basis what we found out was that, you know in that age range the range we've been, you know kind of talking about before which was a spontaneous range from from their perspective 55 to $85,000 per treatment period of nine months from, Georgia.
Yigal Nochomovitz: I have two questions, Renee, on the commercial uptake for Nethicon. First, with regard to feedback from payers, what is your expectation around Nethicon requiring prior authorization? Is it the expectation that the patient will have to have failed the ACER-R? or steroids in order for payers to cover necrotime? And then secondly, what is your expectation with respect to the frequency of therapy? In the commercial setting, will patients, or are you expecting that physicians will treat them beyond the nine-month period, meaning continuous treatment, or will this be sort of an episodic treatment where they're on for nine months, and then they're off for a period of time, and then they resume therapy again?
Basically said that they would you know, and in our view I think would treat it appropriately so they would you know, they would expect it to be you know, the prescription to be done by specialist and all of these patients really do end up but a nephrologist long they would expect it to have you know, that that there would be a diagnosis that was you know valid in terms of the actual disease and and a couple of them did mention that they would get to a step edit in terms of Aces and arms. So that's really kind of what came out of ugh that kind of market research, uh that we uh that we saw and wage obviously in terms if you look at guidelines, you know, that is the only kind of you know, kind of recommendation that the guidelines has is you know to actually treat these patients with a sandwich. I think that you know, as in most indications these patients are already on blood pressure-lowering agents, you know, there's Asus and arms and there's combinations and and they are kind of authors
Renee Aguiar: So what we did, IQVIA did a fairly substantial kind of market landscape research work on our behalf, and so in that kind of research, they did kind of try to address both of these points that you were raising. So from a payer perspective, there was a large amount of payer research that was conducted. I think it covered about 225 million lives in the U.S. And there, in terms of, 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 desks.
Renee Aguiar: But they were obviously shown the Phase 2B profile in that market research, and on that basis, what we found out 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 period of nine months.
Lies and titrated over with a variety of these, uh, you know, kind of basis and arbs to to kind of get to you know, as good of a position that they can but obviously as we know that I'm not really address, you know, kind of the underlying progression which we see in a lot of these patients but as you know, this is obviously something that that, you know, we already do we've already done our trial and on top of optimized Asus and arms, you know, so from our perspective we would expect a blood pressure-lowering agents, you know will continue to be used in in CKD indications, including our general philosophy of life. So we don't we don't really see that as an issue. I must say cuz I think you know pretty much all patients are already on on on and that's what we found also kind of actually in our face to be troubled kids. So so that's really what we found out from from that I think in terms of the the treatment Paradigm, I would say that the the physicians in that market research kind of fell into a job.
Renee Aguiar: They basically said that they would, and in our view, I think we'd treat it appropriately, so they would expect the prescription to be done by a specialist, and all of these patients really do end up at a nephrologist. They would expect it to have, a diagnosis that was valid in terms of the actual disease. And a couple of them did mention that they would look to a 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.
Renee Aguiar: And obviously, in terms of 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-lowering agents. There are ACEs and ARBs, and there are combinations, and they are kind of optimized and titrated with a variety of these kinds of ACEs and ARBs to kind of get to as good of a position that they can.
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. Treatment cycle and then they see these patients three or four times a year anyway, and they would follow them in terms of both egfr and protein area 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. Well, if there's another group of nephrology is to clearly felt that you know, as long as they're patient was seeing a benefit from the medication I could tolerate it that actually they would just prefer to keep their keep the patient on the medication. So I think that there to kind of, you know different approaches. I guess it's 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 woke we 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 you know that there is a continuum
Renee Aguiar: 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 IJ nephropathy. So we don't really see that as an issue, I must say, because I think pretty much all patients are already on them, and that's what we found also kind of in our phase 2B trial. So that's really what we found out from that.
Renee Aguiar: I think in terms of the treatment paradigm, I would say that the physicians in that market research kind of fell into two buckets, really. One group of physicians felt like they actually appreciated the ability to be able to treat patients intermittently. So they actually put patients on a nine-month treatment cycle, and then they see these patients three or four 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, they would put them on another treatment cycle.
Benefit and and you know significant continued Decline and proteinuria, for example over the first three months and this will give us a much longer time. To kind of be able to know that you know, you know better than what we do today and that data is just data that we don't have today and I think that you know from that from that perspective, uh this month obviously something that we're doing both the Nets extend an open-label extension is to provide more really more information and background to these treating the philologists with regards to both of those approaches both the retreatment as well as the extended dosing.
Renee Aguiar: Well, if there was another group of nephrologists who clearly felt that, you know, as long as their patient was seeing a benefit from the medication and could tolerate it, then actually, they would just prefer to keep their patient on the medication. So I think that they have two kinds of, you know, different approaches, I guess what we found from the market research. But that's also obviously why we are going to, on the basis of Part B, we will obviously get a lot of information with regard to the longer-term impact of this treatment, and as we've already indicated, for example, that on the, you know, that there is a continued benefit and, you know, a significant continued decline in proteinuria, for example, over the first three months.
Thank you. That's very helpful. And then just one question on other indications for Africa. I think you had mentioned in the past autoimmune hepatitis. What what's the status of that game planning and other other indications from Network on that? You're that you're targeting.
Yes, so we've had in last year we did have interactions with the FDA with regards to our immune Hepatitis. And we believe that we have we've had very very good guidance. And I think we're we're very close to what we believe is kind of a you know, a clear regulatory path forward which would really involve a late-stage clinical trial in a i h a m a couple of other things a couple more things. We'd like to kind of go back and get some further Clarity on but we would expect in a later this year to to have, you know to kind of have final Clarity on on the way forward in a i h and that obviously would would kind of rely on the same type of of kind of basis in in uh, you know, being able to provide, you know, just a uh-huh. That is more appropriate for kind of chronic treatment than you know systemic steroids simply due to the you know, the the the big difference in in safety profile and particularly in some
Renee Aguiar: And this will give us a much longer time period to kind of be able to know that, you know, better than what we do today, and that data is just data that we don't have today. And I think that... You know, from that perspective, this will also obviously be something that we're doing both in NEF-Extend and Open Label Extension to provide more, really more information and background to these treating nephrologists with regard to both of those approaches, both the re-treatment as well as the extended dosing.
Yigal Nochomovitz: Thank you, that's very helpful. And then just one question on other indications for nephegon. I think you mentioned in the past autoimmune hepatitis. What's the status of that planning? And are there other indications for nephegon that you're targeting?
something of a chronic treatment like age they're obviously compliance and and you know
Renee Aguiar: Yeah, so last year we did have interactions with the FDA with regard 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 in AIH. There are a couple of other things, a couple more things we'd like to kind of go back and get some further clarity on.
Over Mission issues on the basis of what's available today if there's nothing approved. So that's really where we stand in terms of age. We have also obviously previously also discussed PVC wage and we are continuing actually we also have dialogues around and we're continuing those dialogues in parallel, but in terms of a clinical trial, you know, the first clinical trial that will conduct is with set an active in the pivotal Phase 2 3 trial that we are ugh planning to start this year.
Renee Aguiar: But we would expect later this year to have, you know, to kind of have final clarity on the way forward in AIH. And that obviously would kind of rely on the same type of basis in, you know, being able to provide, you know, just a drug that is more appropriate for some kind of chronic treatment than, you know, chronic steroids, simply due to the, you know, big difference in safety profile, and particularly in something of a chronic treatment like AIH.
Right. Thank you very much.
And we have one more question from the line of ram from live side Capitol, please go ahead.
Hey guys. Thanks for taking my question. Just a quick one for me, but based on. Jakaya Texas discussions with you still plan to use GTA as a primary endpoint for the upcoming month or will you focus on instead?
Renee Aguiar: There are obviously compliance and, you know, 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 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, you know, the first clinical trial that we will conduct is with Cetamaxib in a pivotal phase 2-3 trial that we are planning to start this year.
no, since this would be a registration oil potentially registration trial we would we would seek to to use the you know, the validated endpoint if you like, which name is Alt
Got it makes sense. Thank you.
And as there are no further questions, I'll headed 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 three months time and give you a you know, an update as to both our regulatory progress as well as our commercialization efforts in the US.
Yigal Nochomovitz: Great, thank you very much. One more question from the line of Rami Katkhuda from Lifesci Capital. Please go ahead. Hey guys, thanks for taking my question. Just a quick one for me, but based on JICAIUS-X's discussions with the FDA, do you still plan to use GGT as a primary endpoint for the upcoming PBT trial, or will you focus on ALP instead?
Thank you.
This concludes our conference call. Thank you all for attending you may now disconnect your lines.
Renee Aguiar: Uh, no, since this would be a registrational, uh, potentially registrational trial, we would, uh, we would seek to use the, you know, the validated endpoint, if you like, which in PBC is ALP.
Rami Azeez Katkhuda: Got it. Makes sense. Thank you. And as there are no.
Renee Aguiar: 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 three months' time and giving you an update as to both our regulatory progress as well as our commercialization efforts in the US. Thank you.
Operator: This concludes the conference call. Thank you all for attending. You may now disconnect your lines.