Q2 2023 Calliditas Therapeutics AB (publ) Earnings Call
[music].
This call is being recorded.
Welcome to the Cletus Therapeutics Q2 'twenty two.
Three report for the first part of the conference call. The participants will be in a listen only mode.
During our question and answer session participants are able to ask a question by dialing star five on the telephone keypad.
Now I will hand over the conference to speakers C O Rooney gorilla come there.
CFO Jacky Wang song Andrew Odell.
President of North America, and Richard Philip a zoom Philippson Chief Medical Officer. Please go ahead.
Thank you very much and welcome everybody to this Q2 report of 2023.
I would just like to draw your attention to the disclaimer page related to forward looking statements in the meaning of the private Securities Litigation Reform Act of 1995 as amended and I refer you to the company's reports and other regulatory filings, including those which contain risk factors and other relevant information.
So I'm going to take you through some of the Q2 highlights. So in June of this year and we filed our supplemental NDA with the FDA, which is based on the full data from the naphtha Guard phase III trial.
The trial successfully met its endpoint of kidney function as measured by Egfr, which was supported by durability of proteinuria reduction reduction micra, hematuria and the treatment arm and a highly significant benefit for the and ethicon over placebo in terms of total slope.
The first data from the trial was presented to the nephrology community during the era EDTA Congress in Milan in June and the reception was very positive and we've also received very positive feedback from advisory Board meetings held with U S. Nephrologist regarding the phase three data and we're obviously very excited about the recent publication.
In the lamps that are of the data.
So in the second quarter, we saw a record level of 422, new enrollment supports our payout. So we're seeing a continued growth of the franchise are the number of prescribers also continue to grow with Q T seeing over a total of over 1100 prescribers of <unk> compare to only.
Around 300, or so in Q2 of 2022.
Total revenues of 260, my 69 million S. Swedish crowns are about $25 million out of Wichita pay on net sales represented 259, Swedish cramps, which reflects a 39% growth over Q1 and over 270% growth over Q2 'twenty 'twenty.
You too.
Based on our experience to date as you know we are pioneers in this whole area in the sector.
So based on the limited label continued market access friction and potential seasonality impact from the summer period we've.
We decided to revise our 'twenty three outlook to $100 million to $120 million of net sales force our payout for 2023.
In terms of post period events and pipeline updates. We recently shared some exciting data from the interim readout of our head and neck cancer trial, which Richard will cover a bit later in some detail.
And in light of recent clinical and biomarker data advances in the liver area and regulatory interactions, we decided to implement a revision of the trial design of transform which is a clinical trial in PBC, which will enable us to report out read out the phase II data, which is targeted for the first half of 2024.
Please state your name and company.
Please go ahead.
Most importantly enable us to make the most appropriate decision regarding the program going forward.
Including exploring potential different indications as well as partnerships.
<unk>, which we are have been having conversations regarding.
As previously mentioned our phase III data was published in the lancet very recently.
And obviously as you may know obviously the lamps. It is one of the top medical journals in the World are also referred to as one of the big five and so we're certainly very excited about the recent publication and we believe that this really will kick off the dialogue.
With the nephrology community in the U S with regards to the data that we saw in our phase III trial.
So with that I'm going to hand over to Richard Phillips, and our Chief Medical Officer to take you through some of the clinical data.
Thanks, very much Ronnie I'll.
I'll begin by reviewing some of the outcomes of the <unk> final analysis.
So just as a brief reminder of the Phase III study design, then I forgot study enrolled patients with biopsy proven nephropathy proteinuria of one gram per day, or greater and an egfr of 35 to 19 mills per minute and with well controlled blood pressure, whilst on optimized Ras inhibition.
[noise] immuno suppression suppressive therapy was not permitted during the study and changes to antihypertensive medications with discouraged.
This will randomized to receive top payer at a dose of 16 milligrams per day or placebo for nine month treatment period.
An interim analysis of change from baseline in proteinuria and the first 199 patients enrolled and treated for nine months formed the basis for accelerated and conditional approval in the U S and Europe , respectively.
The final analysis of the <unk> study is based on 364 patients and the full analysis set for efficacy treated for nine months and followed up for further 15 months without investigational treatment with a primary endpoint of average change from baseline in Egfr over the entire 24 month period of treatment and observation.
And with Egfr slope based secondary endpoints.
As previously reported the primary endpoint of average change in Egfr over the two year period of treatment and observation was met with a highly statistically significant difference between <unk> and placebo and all additional support to the analyses of Egfr two year total slope.
Were also statistically significant.
When we look at the effect of an ethical treatment on Egfr two year total slope, we see a difference of approximately 1.8 to three mills per minute per year in favor of Mexico compared to placebo, depending on the analysis method used.
All estimates are well in excess of the difference per year and two year Egfr total slope required to predict clinically meaningful long term effects.
Specifically comparison with the meta analysis by increase how has shown that all estimates of the ethical treatment benefit on two year easier fall total slope of well in excess of a threshold of one point to three mills per minute per year required to predict with a high degree of confidence clinically meaningful treatment effects on the composite clinic.
11 point.
Any failure Egfr decline to less than 15 mills per minute or sustained doubling in serum creatinine.
And evaluation of micro Haematuria was also included as a secondary endpoint in the final analysis of the <unk> trial.
This was measured using dip stick testing at each visit during observational follow up a baseline in patients included in this analysis the proportion of patients with Micra Hematuria was 66, 5% and 67, 8% and then ethicon and placebo groups, respectively. In other words the propulsion of PAH.
<unk> and micro hematuria was very similar in the two treatment groups at baseline.
During observational follow up the proportion of patients with micra haematuria decreased to 45% of patients previously treated with <unk>.
As in patients previously treated with placebo the proportion with micro Haematuria doing observational follow up was only slightly lower than our baseline of 61, 2%.
These observations with respect to micro Haematuria further support the potential disease modifying effect of Mexico.
I'd like to take a moment now to discuss our evolving understanding of the long term outcomes and Iga nephropathy.
Isn't published registry analysis of a representative cohorts of patients with Iga nephropathy underscores the poor outcomes observed in patients with the disease and provides evidence that proteinuria levels traditionally considered benign or low risk or in fact associated with increased risk of kidney failure.
This analysis showed that most patients progress to kidney failure within 10 to 15 years irrespective of age of diagnosis with a median kidney survival of approximately 10 years.
The analysis also showed that all patients diagnosed with Iga nephropathy before the age of 40 years and with an annual Egfr decline of three mills per minute would progress to kidney failure in their lifetime, but even an annual rate of Egfr decline a small as one mil per minute would lead to a significant proportion of patients reaching.
Kidney failure within their lifetime.
The analysis confirmed our understanding the proteinuria as a risk factor for kidney disease progression in Iga nephropathy with higher time average protein Europe being associated with greater likelihood of progressing to kidney failure more quickly. However, what was particularly striking in the analysis was the increased risk of kit.
The failure in patients with levels of proteinuria traditionally considered to confer a low risk of progression to kidney failure spin.
Specifically and when considering time average proteinuria levels, 30% of patients with proteinuria, if point for four to eight eight grams per gram and approximately 20% of patients reproach near a lesson 0.44 grams per gram developed kidney failure within 10 years with further emphasize.
As the importance of intervention to reduce proteinuria levels early in the disease course, indeed, the manuscript commented that disease modifying therapies that specifically target the immune system or more likely to be affected early in the natural history of Iga nephropathy before the kidneys accumulate significant irreversible fibrosis.
I'd like to move on now to discuss our interim review of data from the ongoing head and neck cancer study.
Yeah.
As a brief reminder, the ongoing phase two study assessing access in patients with recurrent or metastatic squamous cell carcinoma of the head and neck will evaluate the effect of certain accessible placebo in conjunction with pember, Lizzie Mab on clinical and biomarker outcomes.
Patients with recurrent or metastatic disease, and tumors characterized by moderate or high levels of cancer associated fibroblast or caps are randomized to receive certain actual placebo on top of pember lithium up with tumor biopsies taken prior to enrollment in the game after nine weeks of treatment corresponding to three.
Cycles of Pampers easy map.
Treatment continues until disease progression unacceptable toxicity of patient <unk> investigator decision and patients are followed up for progression free survival.
The planned interim review.
Of clinical and biomarker data was scheduled to occur after 12 patients with paired biopsies tumor had completed at least nine weeks of study treatment.
Data cutoff for the States review was the 26th of May of this year 20 patients contribute to data on clinical outcomes and 12 of these 20 patients had paired tumor biopsies for review.
We evaluated clinical outcomes, such as change in tumor size and disease progression and biomarker changes, including histological and transcriptome make assessments.
We did not perform a review of safety data. Since this is done separately by an ITM C, which reviewed safety data and identified no concerns earlier. This year in March 2nd idea M. C meeting is planned for next month.
The cutoff for this data review seven of the 16 Evaluable patients were progression free with either stable disease or partial response of these seven patients six were in the certain active treatment arm and one was in the placebo arm.
Six of the seven patients were still on the study drug at the time of the data readout of the six patients five were in the <unk> treatment arm and the longest period on drug was reported as 21 weeks and a patient in the sets of Mexico.
Turning to the biomarker analysis and again at the cutoff for this day to review Transcriptome analysis indicated the downregulation of gene expression in the idiopathic lung fibrosis and hepatic fibrosis Parkways was most significant in the patients receiving such a massive competitive placements.
Receiving placebo.
It was also a potentially favorable effect of Cessna exit treatment on the immunological activity of the tumor.
Observed through Fox P. Three staining and the combined positive school.
So in summary at the time of the cutoff for the interim review if Dave. So we saw a numerical difference in progression events and patients remaining on randomized treatment in favor of sets and accept and detect is a preliminary signals, suggesting greater downregulation of important genes and the idiopathic lung fibrosis and that Patrick fibrosis PAH.
Twice in patients treated with sets and accept versus placebo, which is consistent with the mechanism of action of such an exit.
Detecting changes in tumor staining was more challenging because of the small size of tissue biopsies, but nevertheless, we saw some evidence of an increase in the immunological activity of tumors in association with <unk> treatment.
So that completes my part of the presentation I'll hand over to Andy who do.
Thank you Richard.
Next slide.
So during the second quarter of 2023, <unk> commercial team continued to build on the achievements from the previous quarter further reinforcing the position of <unk> payout as a transformative and foundational treatment option for Iga nephropathy net sales of $25 million in Q2, representing a 39% growth over Q.
In addition, our specialty sales force generated 422 enrollments during the quarter, which represents further growth coming off a Q1 record of enrollments and brings the 2023 total to 831 at mid year.
This strong 85% growth compared to the first half of 'twenty two and the addition of 232, new prescribers during the quarter underscore the growing recognition of <unk> clinical value among health care providers.
In the second quarter over 90% of the patients enrolled in <unk> payout touch points, excluding those still waiting for the final insurance decision received her pale in addition, compared to the first quarter, we saw a 14% improvement in the average time to fill reflecting our continuous investment in supporting providers and patients.
And accessing tour payout next slide please.
During the second quarter, our medical and commercial teams had a robust presence at major nephrology conferences, including National Kidney Foundation spring clinical meeting and the European Renal Association Congress held in Milan in June .
DTA proved instrumental in cleaning tasks of scientific exchange efforts with Napa Guard pivotal data receiving recognition as a late breaker presentation. This mark the scientific communities first encounter with these critical findings capturing the interest level of nephrologist around the globe.
Additionally, abstracts with valuable data on proteinuria and Hematuria. We're present, we presented from the full Napa Guard study population, which further demonstrated the uniqueness and benefits of <unk> in the treatment of <unk> again.
Discussions at E. R E D T a centered around the evolving ICANN treatment landscape and the importance of the immuno modulator therapies to suppress pathogenic Iga production and control Merial information highlighting to our payers pivotal role in the treatment paradigm.
<unk> has and will always remain dedicated to Iga nephropathy patients and caregivers are patient and advocacy support is unwavering.
Early in Q3, we let the sponsorship and support of the Iga Nephropathy Foundation second annual in person patient summit called Spark. This event is extraordinary and special it's.
It's filled with approximately 200 patients that are eager to learn connect support smile cry and even dance together.
Tenants at the event as motivation and confirmation to our team members that focus on access availability and education of Iga nephropathy on a daily basis next slide please.
We've seen very rapid and significant growth from the launch of our product delivered by a dedicated team with great execution capabilities. However, due to primarily two factors or indication on label during accelerated approval and the market access friction that while it's typical for specialty products is new to many in the nephrology spur.
<unk>, we are revising our guidance.
As you are aware our indication during this accelerated approval period is based on proteinuria reduction and describes rapid disease progression is generally a UPC are of greater than or equal to one five grams per gram. While this is not a cutoff some payers do manage more strictly to the one five grams per.
Graham, which has skewed the initial usage of tar payout towards patients with a higher <unk> level, which has reduced the addressable market size compared to the population represented in our pivotal trial, which aligns with how rapid progression as defined in the <unk> guidelines.
As it relates to market access as we've mentioned previously at a given time approximately 15% to 20% of enrollments are still in process. This typically means that the enrollment cryo as more information or theyre going through the approval of the appeal process with payers, which can require some back and forth between Payor Nephrology office and our hub.
What's our payer coverage is broad with over 90% of U S. Lives have been coverage, we are seeing that between five and 15% of enrollments did not ultimately convert.
Due to a variety of reasons. This is most often due to payer management, which while it's typical once again for a specialty drug has several inexperienced and under resource to office staff unwillingness to go through the process, which can include appealing initial payer decisions. This is different from other disease categories such as <unk>.
Apology or rheumatoid arthritis, where payer management as expected and integrated into the <unk> office workflow and providers generally understand how to navigate payer management using clinical rationale.
While we have many patients that have received longer than nine months of therapy. The average duration of therapy over the last 12 months is approximately eight months long as we've heard from some of the top kols that are familiar with our product and the full study results that were published in the lancet. This week to our payer works differently than any other product.
And this requires education and time to disseminate to prescribers and change long lasting habits, and how they've treated again and these patients for many years next slide please.
We continue to center efforts and resources on education and market access support and remain confident that we will demonstrate continued growth and enhanced sales trajectory following full approval in the broader population due to the following.
First full approval reduced payer limitations.
And wood on the basis of approval and the full trial population substantially increase the size of the addressable market.
Market access friction will continue to decline with the additional resources, we put forth and also be supported by a full trial results from naphtha guard being published and the expanded scientific exchange of information that is anticipated with payers and nephrologist, while we move towards full approval and a new label.
Physicians will gain further confidence with continued use patient success stories as well as familiarity to the data of both Napa Guard trial as well as our open label study extension study, which will conclude in the middle of 2024.
Once again I want to reiterate our strong anticipation of substantial growth from our full approval in a broader population and the general confidence in the differentiated and groundbreaking benefits of our product and the caliber of our team as we move through the second half of 'twenty, three and beyond and beyond So please move to next slide.
As I turn it over to our Chief Financial Officer Fredrik Johansson.
Thank you Randy and good afternoon, and good morning, everyone. I will now present to you the financial overview for the second quarter of 2023 and as always all numbers presented to you our median sick unless otherwise stated to.
To start we report tune of six to $9 4 million in net revenues for the quarter for the same quarter last year, we reported net revenues of $64 million.
Net product sales for the quarter amounted to $259 2 million or $24 7 million, which is an impressive 39% growth from Q1, and a 275% increase over the same quarter previous year.
In addition, we also recorded $10 1 million for the quarter and revenues related to partners, primarily from can peg royalties from startup.
With total operating expenses for the quarter amounted to $333 million compared to $271 5 million for the same quarter last year.
The cost for R&D decreased by $7 3 million in the quarter to $89 million compared with $96 3 million for the same quarter previous year.
The decrease in R&D expenses Arena is primarily from the in all lessons completion of Donetsk art start in the first quarter 'twenty to 'twenty three reducing the trial cost in Q2 compared to the same quarter prior year.
While designing a study in PBC transport is currently under review in the short to start that has the potential to significantly reduce the planned R&D cost for the trials for both 2024 and 2025.
The cost for sales and marketing increased by seven 8.2 million to $191 5 million compared to $113 3 million for the same quarter previous year.
The increase is primarily related to the cost for sales and marketing of <unk> in the U S where the marketing activities has been intensified in the sales force has been increased compared to the corresponding period of the prior year.
The above led to an operating loss of $75 2 million for the quarter compared to $209 8 million for the same quarter last year.
And we did continue to reduced operating loss quarter over quarter as sort of payer sales are growing.
In the second quarter cash used in operating activities was $163 million compared to $225 2 million for the same quarter previous year.
This leaves us with a net decrease in cash in the quarter of $167 1 million and we have a very healthy cash position at the end of the quarter of $866 2 million, which we believe is sufficient to take us to profitability.
That was all for me, Thank you and now back to you Renee.
Thank you very much we're ready to take our questions. If there are any.
If you wish to ask a question. Please dial star five on a telephone keypad 10th re queue. If you wish to withdraw your question. Please start star five again on a telephone keypad.
First question comes from <unk> Divan Guggenheim Securities. Please go ahead.
Hi, Thank you for taking my questions and for all the color on the call just a little bit around the guidance and some of that.
Since you have room, so when the market access friction in Poland.
Since you mentioned will resolve some I know you've filed now for the full approval assuming you get that early part of next year.
When do you sort of expect some of these friction time points to cut it.
Would that be sort of first half of next year is a more like second half of next year or is it more of a 2025, just just trying to get a sense.
The timing there.
And then I have one quick follow up.
Sure.
So I guess the interactions with payers, obviously can can be initiated I would say kind of out of this period of time. When there is kind of a peer reviewed journal.
Manuscript out there that's been published.
But obviously these processes do you take awhile and ultimately payors are going to be guided not just by kind of published data, but obviously also what the ultimate label will say and that obviously they will have to take into consideration. So my assumption is that we will start definitely start seeing this.
2024.
But obviously it'll be kind of you know over time this will build in 2024 as more and more payers.
Has the opportunity to kind of take this through there there are process I don't know if you have anything to add any.
No I agree I think it's over time and experience from those that don't have the staff to support and Thats.
What we've improved on thats somewhat of that.
That's something that we can assist with but as it relates to payers in their decisions and formulary for that which will also ease it. It's as Renee said once our labels changed or guidelines come out. These are kind of important pieces of information.
And how a payer decides to manage our product.
Yeah.
Okay, great. Thank you and then one quick follow up just in terms of I'm sorry.
Sorry, if I missed this on the call, but just in terms of the duration you're seeing of treatment is there any comment you can give there in terms of sort of the ninth month seller studied what are you seeing in the real world now in terms of how long patients are generally staying out there.
Yeah, No I think as we've said before I mean, obviously, it's a it is a very it's a variable.
The time that people stay on treatment, but obviously as we've also mentioned for those patients who reached nine months a majority of them actually stay on beyond nine months.
But I think that's why we really needed to have a slightly longer time series, where we could look at this because it does vary and I think that's why we kind of today would say that the best kind of estimate to use for right now it's probably eight months.
But obviously, we would expect that to.
It kind of too to be extended to longer periods of time as kind of the physicians have more experience of the product more data comes out at.
Etc, Andy anything you want to add to that.
No I think that Thats right we have.
Many patients on greater than nine months now.
But that's just to assist with their overall average seems to be around eight if we look back the last 12 months or so.
Okay. Thanks for taking my questions.
Our next question comes from Christopher IATA Seb. Please go ahead.
Yeah.
Yes, thanks for taking my questions.
So a couple first on TARP.
<unk>.
So are you seeing any signs now that were I guess, a little more than halfway through this quarter have any pick up enrollments and enrollment since the data was presented or is it too soon.
Then.
In terms of the clinical program would it be wise to consider a trial in patients with low levels of proteinuria.
Given the data that you.
Rented.
At the conference in today, and if so what can you tell us about the impact of dose level on proteinuria decline in patients at the lower end of baseline proteinuria in the Nerf again, so the phase II trial.
And then I.
Have a couple on.
One certain accident as well, but I'll wait for that thanks.
So I think it is too soon to your first question I think it's too soon to kind of draw any conclusions from that I think we're going to have to wait for that.
In terms of your second question I think that this is.
We haven't seen in terms of the trial any kind of.
And the difference in terms of the effect of people, having lower or higher levels of proteinuria. It is quite consistent across kind of baseline you Pcr levels.
But what we are seeing and I think this is something that you bring up which is an excellent comment which is obviously part of what is being done in this whole sector is that there is I think building slowly, perhaps but they're certainly building more of a sense of urgency and that is coming from the fact that there is now reported data and there's actual Egfr day.
There is placebo data and I think that all of these things will contribute to the fact that what we're hearing is more and more of that actually it's becoming more of an impetus to treat early and pacifically with something that has the ability to really significantly impact egfr in egfr trajectory.
So it is moving away to some extent from kind of symptoms to actually more.
Hard data because that data is now becoming available and yes, I think it is moving towards.
Physicians actually realizing that this is something that you can't just kind of wait for and potentially have a benefit on proteinuria or you really need to treat this in order to keep kind of patients out of dialysis hopefully.
So I do think that that is something that we're going to see more and more of them and I think yes. It will it wouldn't surprise me if the kind of levels will move down in terms of which patient population.
Should be considered for treatment compared to kind of where it's been previously.
Okay. Thanks, very much and then if I could quickly just.
Throw in a couple of more of a sort of sudden acts of in head and neck.
How many evaluable patients where they're in each arm.
And then for nothing guard.
So.
Some experts have written that in part a of the placebo group outcomes underperformed versus outcomes in other trials like testing.
What's your view about that.
Any potential causes.
Richard do you want to.
In terms of the balance between the treatment groups at the time of that interim review of data. They were essentially balance I mean, I think for the biomarker analysis or 12 patients.
I think seven were on placebo five on Cessna exit.
And overall in the 'twenty is pretty balanced so.
In terms of them they are still kind of on the unethical placebo arm I think this is Tom.
I don't know if it's actually I mean in my view I think this is something that again I think we'll see more and more of this is I'm actually kind of more trials come out, but I'm actually heard both of these that supposedly we had much too too much kind of decline in placebo arm compared to what people would expect them suddenly put their people are saying, we have too little and I think that at the end of the day.
I think it's a it's a very similar to what we saw in our phase two b.
I think it's it's actually very similar to what's been seen in other trials, where theres been placebo arm and so I don't really think that it's it's you know kind of relevant or helpful to really start kind of comparing one trial to another trial I think you can pick and choose a variety of trials then.
To do that so I think overall that it.
These are you know it.
It is eight.
This kind of patient population group that is at risk of progression do you seem to have.
Now a fairly similar kind of development of the placebo arms and I don't know if you have it I completely agree I mean, I think we've looked at this in detail I mean, our view is our placebo decline in terms of Egfr is absolutely in line with what would be expected in this category of patient population and as Ron has said and.
Hopefully through what I talked about during the presentation that it underlines the importance of early intervention patients.
One placebo, who receive supportive care only there is a significant risk.
<unk> pro.
<unk> trends get stage kidney disease.
In a relatively short period of time 10 to 15 years. So that to me is the key message is coming from the placebo group.
We've found nothing that suggests a placebo group is behaving in anyway unusually absolutely reflects that patient population that was enrolled.
Okay. Thank you.
Let's take the next.
Question.
Next question comes from <unk>.
I'm not sure mortgage from Citi. Please go ahead.
Hello Graham.
Yeah, we can hear you yeah, Hi, Irene can you just re explain I know you've probably explained this in the past, but in the paper Youre seeing obviously theres no convergence in the slopes on the Egfr.
After the <unk> during the observational study, which is obviously strong.
Disease modification, regardless of the.
The split by area, but then in the in the Proteinuria graph you see either after the 12 months you do start to see a rebound.
So can you just help explain why youre seeing the continued disease modification on the egfr side of things but.
On the PCR side.
You know things are starting to converge. So I was just curious if you could maybe reexplain the thinking around that.
Yeah.
So I guess I'll I'll give my view and Richard you can provide your commentary. So I guess my view is actually this is I mean this is kind of when we're starting to look at the relationship between kind of proteinuria and Egfr and maybe it is slightly more complex than what people had actually thought or how you kind of simplistically can can explain.
And so we your cap slightly right. We are not seeing a kind of first a significant reduction in proteinuria, followed by an impact on Egfr there seems to be a more complex relationship between proteinuria and egfr than what may have been kind of depict it in in various papers and I think this is really when were going to start seeing this.
In terms of you know.
Different modes of action different drugs, they may very well have a different impact on proteinuria and Egfr and so I think that you know will probably won't have kind of one size fits all here I think that we will very well may see quite.
Quite big differences in terms of proteinuria versus Egfr and I think this is something that we're just going to have to rely on on the datasets that are going to become available to.
To see them you know in terms of what this relationship kind of looks like and if its actually constant or not.
Based on the different modes of action Richard Yeah, I mean, I agree I'm not sure I can add too much more but as <unk>.
We've observed I mean, clearly there is evidence of the disease modifying effect with the maintenance of the separation of the Egfr curves over the second year, where patients are not receiving treatment, but as Ronnie has said I think this opens the door to.
Recognizing.
There's no there isn't necessarily a completely simple relationship between proteinuria change and a change in egfr trajectory over time, and I think you will see different patterns of relationship between prices in Europe and Egfr change.
Related to the mechanism of action of the treatment.
Okay.
And then just one very specific question are you able to say anything more about this.
The split or the percent of patients that have received her payout so far that are above versus below this one five gram.
Border.
I don't actually have the I don't know Andy do you.
No no we don't we don't.
Have the exact numbers on that.
Okay. Thank you.
We have the next question from Nick.
Garuda lifestyle capital. Please go ahead.
Yeah.
Hey, guys. Thanks for taking my questions as well.
You touched upon the average duration of treatment with <unk> being around eight months are you hearing any physician feedback as to why patients may not be completing the full treatment course is it primarily due to aes or are there other factors involved here.
And it will take that.
Sure. There's several factors obviously, there is always there could be <unk>, but.
What we're seeing is interestingly, we've asked some physicians and sometimes they are saying its been successful the drug.
And you remember the typical treatment length of therapy for a product, it's probably replacing them.
A lot of instances or systemic steroids and they typically prescribed them for about six months. So interestingly a lot of times, they would even say well none of this patient had success and they stopped less than six months and this goes to how this product works different.
<unk> talked about even on the last question people stop taking the drug in their proteinuria continued to decline, let's remember they stop taking the drug while they're egfr stayed stable. So so this drug works differently and I think it's going to take time for people to get used to a initial treatment.
<unk> of nine months.
But as we said earlier there it's pretty variable right now we have people that are.
On for well over nine months some that are on.
767 months and deeming our success and then stopping as well.
And this doesn't speak to let me just make one other point this doesn't speak to re treatment, which which is obviously something that's going to start to happen more and more.
Got it makes sense and then really quickly with regard to the interim data with <unk> of the patients on treatment who are progression free can you touch upon how many were actual responses.
Relief patient's treatment naive or refractory coming into the study.
Well in terms of treatment. They may have risen because these are patients with recurrent or metastatic disease disease. So they will have received.
<unk> treatment, probably an initial treatment plan that could have comprised anything.
Any combination of radiotherapy chemotherapy and surgery before they come into the study with a recurrent or metastatic disease.
And we haven't given that level of granularity around.
The various responses.
Fair enough thanks for taking my questions.
Our next question comes from Annabel Sammy y.
Please go ahead.
Hi, This is Jack calling on for Annabel, Thanks for taking our question.
So I know, it's not a hard cut off but you've previously previously mentioned requesting a change of the full label language patient to generally greater than eight grams of protein area from the $1 five like it is now.
What influenced the selection of that particular number in the context of that long term outcome study you discussed on the call and about what additional percent of the overall Iga and population with that capture for the payers to treat that number like hard cutoff.
So just to just to kind of make sure that I kind of understand your question. So obviously the the 1.5 is it's a UPC are at level. That's in our label right now, which really obviously really wants to kind of drive usage towards.
Patients who are at risk of rapid disease progression.
0.8 of UPC or is the actual kind of level of inclusion into the phase II trial.
Which is the method guard trial, so that obviously is consistent with the kind of one gram of proteinuria.
Which is in the Conagra guidelines and represent the broader population at risk of progression. So this would obviously go from in a kind of having a fairly fairly limited kind of.
Part of the kind of population at risk to include the full population at risk.
And so obviously, what we've said is that the estimate that we have for this is that you know, 50% or just over 50% of the population.
Is kind of expect it to be at risk of progression and therefore may kind of fall into that type of category. It's in obviously, a very it's quite a significant broadening of the.
Kind of them patient population.
In terms of the label.
In terms of kind of how big exactly this kind of subgroup is I think it's really almost impossible to know I mean, Unfortunately this is a rare disease and we don't have a lot of data.
About you know the prevalence the population or are these kind of the sizes of subpopulations.
I think we're not really unfortunately able to comment on exactly how big that would be but we know obviously that it's significantly smaller than the overall population at risk, which was studied in the phase III.
Great. Thank you.
Next question comes from Dan acuity.
Total Securities. Please go ahead.
Yeah.
Thank you for taking my questions.
First question would be on the enrollment so Q1 was a bit slower than expected.
For almost eight the now expanded 22, so the pace is not really increasing they expect.
Slowdown in Q3, and now because of the summer holiday.
What's your explanation of it.
The increase in EBITDA.
So again I think that what we've what really what we're seeing is that you know there is a it is a function of the fact that actually there is some market friction in this area. We don't have you know physicians are not necessarily seeing the sense of urgency.
In terms of actually kind of wanting or needing to treat patients kind of immediately.
What we are seeing is a very steady growth I think obviously also new subscribers.
We're adding to this.
And so I think that even if we haven't necessarily kind of reached a very significant.
Inflection point I think that obviously the franchise.
Now with the kind of growth that we're seeing in revenues et cetera, I think is having a very healthy growth trajectory.
Overall, I think that in terms of when would we kind of potentially have that change I do think that you know it does come back to them.
Not having accelerated approval not having a kind of a smaller subgroup.
And also I think obviously, having more data out there for.
For people to really understand because that's as we've mentioned I think this is this is differentiated from everything out there in terms of that it is not a generally systemic approach to.
Trying to kind of impact proteinuria. It really is a kind of local approach really focused on being disease, modifying and really kind of having an impact on the kidney function. So I think that there is an educational component of this.
But in terms of the the summer again, it's it's I think what we have so what we can expect potentially to see that seasonality again during this kind of Q3.
And I think it's it's hard to know whether we are going to experience that or not but it's certainly something that were you.
Taking into account that.
That might be the case and that's obviously also one of the reasons for our revised guidance.
Okay. Thank you.
You mentioned the clinical data.
So far unique zone.
The GFR effect.
Helpful.
The feedback.
Sufficiently we're guessing that considering that there is no.
Sure.
Driving the market has shown this effect.
It's a progressive disease that there is no.
Interest interested to prescribe the drug itself, maybe again bill labor related.
Okay.
There's something else that you see.
I think even I think it is a combination of the fact that you know this is very name in the renal the renal area has not seen lots of specialty products to start when it is not something that you know nephrologist deal with you know as you know it's not like they have 100 drugs to kind of choose from their old specialty that they know exactly how to manage so I think there.
Is clearly kind of in a process here to go through them and so apart from the fact that you know this is a specialty product and it is not you know not that well established I think that there is part of that is the sense of urgency I think that a lot of these data sets that are coming out in hours and we just talked about a dataset from registry that real.
I think is shedding light on this for physicians to kind of say listen you know you may not have a patient who's going to have an event in the next six months, but this patient is going to end up in dialysis unless you actually treat this disease and treated fairly aggressively with a focus on actually stabilizing their kidney function.
And I think that we will see more and more of this is actually this this data is making its way into the nephrology community and unfortunately, it's not it's not immediate there is a kind of educational process here, but I have no doubt.
But there will be you know.
More and more kind of information and I think that the nephrology community.
You know is very data driven and I think the more data that comes out there are they will review it and they will start making.
Decisions around treatment paradigms and how to best.
Reserve kidney function for their patients.
Okay. Thank you and our last follow up.
Europe , How's the progress there and that's been.
Fairly close so far.
Yeah. So I think that what we've generally what's I think is seen in Europe from from you know from any kind of a launch in the kind of medical products is that you know it does take a lot longer in Europe , obviously, because again of the the difference in them negotiation cycles and difference in terms of of.
Country by country kind of launch.
But I think in terms of the you know in terms of start I think they are they are very happy with the progress that they're seeing.
I think that they've started to kind of now launch also in some other countries and so we would expect to start seeing you.
Again, some of that kind of additional revenue coming from other regions outside of Germany, but minus my understanding really isn't what we're hearing from our partner is that they.
They're very happy with it relate with the development and I think here you know EMA really did put a quite a strong kind of line in the sand in terms of they did not use the word generally and.
So I think here it is very much limited to just that population.
Kind of 1.5.
You Pcr level.
Which again I think we have to kind of take into account.
When looking at Europe .
Okay. Thank you very much.
Our next question comes from Maurice Raycroft from Jefferies. Please go ahead.
Hi, Thanks for taking my questions wanted to clarify does the market access friction, resulting in the 5% to 15% not converting does that include the patients with UPC are less than 1.5 Gram per Gram and also wanted to know.
Any of the market access friction issues are due to competition with <unk> launch.
So I would say that I would say the answer to your first one is yes. Obviously this relates to the entire population that prescribers are prescribing for <unk>.
So obviously some of the reasons why you know why there is frustration.
From a physician's perspective in and why they are you know they kind of ultimately may may choose not to go forward is because of the fact that the payers are potentially.
Potentially giving them at a difficult time, if theyre trying to prescribe for a patient that has a lower levels.
I think in terms of of payers I I I I wouldn't expect any of that to have an impact us I think that you know.
This is a process that other companies are going to have to go through.
You know the Pnp committees and get you know, they're kind of use on them, but I don't think that you know them.
I don't I don't think we have any kind of impact on that from a payer perspective, but Andy I don't know if you have a different view on that Andy.
No I don't think.
I don't think they have an impact.
I think with what is the.
Definitely clear there are definitely patients that are at or above.
Eight and in less than the one five that have there.
The time is that that's where they're seeing some friction clearly that that's where it is.
Might get these patients that arent failed or are these.
That arent converted to your first part of your question.
I've also seen situations, where actually it's very severely.
Sick patients.
That actually you know you are prescribing for someone who may actually be a have lost a lot of kidney function.
And actually they may actually get on and get onto the the transplant.
You can get into the transplant Q and therefore, you know.
We will not kind of complete a carry or take kind of the drug. So it is really quite different I mean, theres quite a variety of reasons I would say why not just the fact that it is below it can be a variety of other reasons as well and also actually being.
You know quite far progressed can obviously be another reason why.
There is a.
Frustration our decision not to kind of go forward.
Got it that's helpful.
Any impact with on <unk>.
Due to competition.
But I guess, it's I mean, it's impossible for me to know I mean, I'm, assuming that every time that you have kind of a.
Another kind of company coming into the market you would expect that you know there would be some impact from that however, I think also that.
You know this is a very early early stage in the launch I think that you know it's been very limited revenues, so far but I haven't really I mean, I don't have any insight into.
How that launches being run or what they're seeing or how they're kind of progressing well there. So I think from our perspective, we're kind of focusing on on kind of our market and in building our franchise.
And again I think that the you know ultimately the data.
The strength of the data will ultimately decide how physicians will derive their treatment paradigm and so I think it is as I've said before it's clearly an extremely data driven.
Great.
Again, you know they don't like to go through specialty products I'm sure. If you gave them free drug and they will definitely like that on the other hand, I think that you know the the the actual kind of decision a medium term, we'll clearly be based on what is the patient profile I have a front of me how will I actually kind of treat that patient best base.
On the needs of this patient and then I think you will have a variety of different options.
Which I think is great for the patient.
And then I think that as you know the physician will make the appropriate decision based on the data that they have in front of them. Mr. Hao. The motive action now the type of drug et cetera.
And I think that's ultimately where we're going to to end up.
Okay. That's helpful and it makes sense and maybe just one other question and then I'll hop back in the queue.
I'm just wondering if you can thinking about the longer term opportunity wondering if you can elaborate on the open label extension study and how that's going if you have any insights from this study as far as how many patients have enrolled and how they're responding to the second round of treatment.
Do you want to take that my true Yeah, I mean, I think that study is going well. According to plan. We expect as Andrea said, we expect to have data from that study in the middle of next year.
Third 19 patients were enrolled in that study most of those patients have.
Completed the treatment I think we have around about 16, continuing in this study at the moment.
Dropout rates have been relatively low.
And as we've said before I mean, I think we saw when with patients who are coming in that one of the main reasons patients one guessing in was because of they weren't meeting the proteinuria requirements and we can see why now that's reflected in the.
Stained improvement in proteinuria that we saw in the second year of follow up in the main study.
So that that then translated through to fewer patients being able to get into the open label study, but I think that studies as I say to reiterate it's going well, we expect data to come out in the middle of next year and I think that will be very important information to help us understand.
The potential benefits to the second course of treatment.
But to be clear, obviously that is still blinded and it's so we have no insights into any data readouts or or anything anything as such.
Got it okay. Thanks for taking my questions.
There are no more questions at this time, so I'll hand, the conference back to speakers for any closing comments.
Thank you very much. Thank you for the questions. Thank you for listening to our Q2 report and we look forward to speaking to you again, when we report our third quarter.
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