Scott Smith - CFO Jan Mikkelsen - President and CEO Jonathan Leff - Chief Medical Officer.
Jim Birchenough - Wells Fargo Securities Jessica Fye - JP Morgan.
Welcome everyone to the Ascendis Pharma Year-End 2017 Financial Results Conference Call. Following some prepared remarks from the Company, we will open up the call to Q&A. I will now turn the call over to Scott Smith, Senior Vice President and Chief Financial Officer at Ascendis Pharma.
Sir?.
Thank you, Operator. And thank you everyone for joining our year-end 2017 financial results conference call today. I'm Scott Smith, Chief Financial Officer of Ascendis. Joining me on today's call are Jan Mikkelsen, President and Chief Executive Officer, and Dr. Jonathan Leff, Chief Medical Officer.
Before we begin, I would like to remind you that this conference call will contain forward-looking statements that are intended to be covered under the Safe Harbor provided by the Private Securities Litigation Reform Act.
Examples of such statements may include, but are not limited to, our potential to become a leading integrated rare disease company, our progress on our pipeline candidates and our expectations with respect to their continued progress, statements regarding our strategic plan, our goals regarding our clinical pipeline of rare disease endocrinology programs, statements regarding the plans for our Phase 3 heiGHt Trial of TransCon Growth Hormone and the fliGHt and enliGHten trials, statements regarding our Phase 1 trial of TransCon PTH, statements regarding the market potential of our pipeline candidates, and statements regarding the planned regulatory filings.
These statements are based on information that is available to us today.
Actual results or events could differ materially from those in the forward-looking statements and we may not achieve our goals, carry out our plans or intentions, or meet the expectations or projections disclosed in our forward-looking statements, and you should not place undue reliance on these statements.
Our forward-looking statements do not reflect the potential impact of any in-licensing agreements, acquisitions, mergers, dispositions, joint ventures, or investments that we may enter into or terminate. We assume no obligation to update these statements as circumstances change, except as required by law.
For additional information concerning the factors that could cause actual results to differ materially, please see the Forward-Looking Statements section in today's press release and the Risk Factors section of our annual report on Form 20-F filed today. On today's call, we will discuss our year-end 2017 financial and business results.
Following some prepared remarks, we will then open up the call to questions. I will now turn the call over to Jan Mikkelsen, our President and Chief Executive Officer.
Jan?.
TransCon GH, TransCon PTH, and TransCon CNP. During 2017, we continued this transformation of Ascendis from a company with a single product in the clinic to having a pipeline with multiple rare disease candidates in clinical development.
You will recall that our three endocrinology product candidates are created by the same unique combination of our TransCon technology together with our [indiscernible] for product innovation.
Our rare disease endocrinology pipeline is built on [indiscernible] with established safety and efficacy, which is expected to provide a higher success rate compared to traditional drug development. This expected higher success rate is becoming evident as we further de-risk our pipeline by successful clinical progress.
Our organization continues to evolve gradually [ph] as we prepare for our programs to invent through the clinic and towards commercialization. We are executing step by step on our plan to build a leading integrated rare disease company. I would like to briefly review the [indiscernible] with each of our product candidate.
Our TransCon Growth Hormone program continue to advance in Phase 3. We completed enrollment in our pivotal heiGHt trial, and initiated two supporting Phase 3 trials. We also continue the development of our patient-friendly auto-injector, which we expect to be ready at norms [ph].
In addition, we published our Phase 2 results and other data to build awareness of our potential best-in-class program. Given changes in the competitive landscape during 2017, TransCon GH has moved to a potential first-to-market position in their latest wave of long-acting growth hormone products for pediatric growth hormone deficiency.
We are well-positioned in this market, and we expect top line result from our heiGHt trial in the first quarter of 2019. For TransCon PTH, we initiated our Phase 1 trial last year. Since January, we have been reporting interim data from both the single and multi-dose cohorts.
This positive data reinforce our preclinical finding supporting the target product [indiscernible] for TransCon PTH as a true replacement therapy. By restoring PTH to physiological levels for 24 hours a day, both serum and urinary calcium should be normalized.
We expect to complete this trial in the second quarter, and we will report data at medical conferences and business update. We expect to initiate Phase 3 in the first quarter of 2019 pending regulatory discussion later this year.
For TransCon CNP, we submitted regulatory filing in Australia, and have now received approval to initiate a Phase 1 trial as planned. We're on track to dose subject during the second quarter, and have top line data in the fourth quarter of this year.
As I reflect on the year one significant achievement is the translation of TransCon PTH preclinical data into clinical data. Once again, highlighting [indiscernible] of our TransCon platform technology. This gives me a high level of confidence that TransCon CNP has the potential to realize its target product profile.
We expect to report the clinical data in the third quarter this year supporting our goal to provide patients with FGFR-related diseases and effective treatment without cardiovascular risk. All three of our candidates are now advancing [technical difficulty] business.
The product profile and data so far has been well received by both the medical and patient communities. It is clear that our pipeline address significant unmet medical needs. I would also like to remind you that each of our internal pipeline programs is wholly owned without royalties to third parties.
We are building our commercial infrastructure and put in place the key functions requiring to support pre-launch activity and commercialization of our differentiated product candidates. You may recall that one element of our Vision 2020 is to pursue additional new therapeutic [indiscernible].
We are eager to develop the same kind of high-value pipeline we have developed for endocrinology [indiscernible]. We plan to address unmet medical needs using the same [indiscernible] used for our current pipeline.
By the events in our rare disease endocrinology pipeline and in achieving our stated milestone, we also remain on track to this part of the Vision. Thank you for your support during a super year for Ascendis. I will now turn the call over to Jonathan..
Thanks, Jan. 2017 was a defining year for our pipeline. We now have three product candidates advancing in development, and we have met all of our stated milestones. With this growing pipeline we are maturing as a company and expanding capabilities in our clinical and regulatory. Our Phase 3 program for TransCon Growth Hormone is progressing well.
We completed enrollments of 161 subjects in the pivotal heiGHt trial, exceeding our original target and further strengthening the statistical power of this non-inferiority trial. The Data Safety and Monitoring Board has extensively reviewed our safety data and recommended continuing our program as planned.
At the recent ENDO conference in Chicago, we presented a poster summarizing the baseline demographics of heiGHt trial subjects. The poster concluded the demographic profile is generally similar to the daily growth hormone cohorts of four recent Phase 3 registration trials.
Based on final subject enrollment, we calculated the trial's statistical power for non-inferiority to be well over 90% even based on conservative assumptions. Our Phase 3 single-arm open-label fliGHt Trial is also well underway. Our plan is to recruit 150 subjects who will switch from daily growth hormone to once-weekly TransCon Growth Hormone.
The fliGHt trial is enrolling briskly, and we are extremely pleased with the strong interest from sites, most of which are also participating in the heiGHt trial. Investigator enthusiasm for the trial also suggests strong interest among patients treated with daily growth hormone to switch to our long-acting therapy.
We believe this is an encouraging indicator of the unmet need for long-acting growth hormone treatments. We expect to complete enrollment in fliGHt in the third quarter of 2018. We also recently initiated the enliGHten trial, our long-term extension study with the initial subjects from heiGHt rolling over in recent months.
Feedback from sites has been encouraging, and we expect the vast majority of subjects finishing the heiGHt and fliGHt trials to enrolling enliGHten. As Jan mentioned, we anticipate top line results from the heiGHt trial during the first quarter of 2019.
Based on expected availability of data from heiGHt and the supporting Phase 3 trials, we are on track towards our stated goal of a database lock for the entire clinical program in the third quarter of 2019. Turning now to TransCon PTH, we have made exciting progress with this program in the past year.
As a reminder, TransCon PTH is in development as a true PTH replacement therapy for hypoparathyroidism designed to more fully address all aspects of the disease.
Following initiation of our Phase 1 trial last year in healthy adults, we are thrilled with the interim data so far that supports our target product profile, a convenient therapy that restores PTH to physiological levels with an infusion-like pharmacokinetic profile.
We believe that by replacing and maintaining PTH levels for 24 hours a day, TransCon PTH can normalize serum, calcium, and phosphate as well as urinary calcium excretion.
Such a product may not only control acute symptoms of hypo or hypercalcemia, but also may help reduce the long-term effects of hypoparathyroidism such as tissue calcinosis and renal impairment. Currently, available treatments do not fully address all aspects of the disease.
In January, we presented initial findings from the Single Ascending Dose or SAD portion of the ongoing Phase 1 trial. Pharmacokinetic data from the SAD cohorts demonstrated a half-life of approximately 60 hours supporting an infusion-like profile with daily administration, and reinforcing our prior preclinical evaluations and modeling.
Importantly, this half-life is a substantial increase in duration compared to subcutaneous administration of PTH 1 to 34 and PTH 1 to 84, both of which have half-lives of only a few hours. Finally, the SAD data also showed sustained and dose-dependent elevations of serum calcium levels lasting more than 72 hours with low intersubject variability.
Earlier this month in a late-breaking poster at ENDO, we presented additional data, notably results from the Multiple Ascending Dose or MAD cohorts. These data further reinforced our target product profile for TransCon PTH. Following 10 daily doses, free PTH levels showed a flat infusion-like profile and a low peak to trough ratio over 24 hours.
The MAD cohorts also showed a predicted pharmacodynamic response, suggesting the ability to titrate patients with hypoparathyroidism into the normal calcium range. For example, measurable increases in serum calcium levels were demonstrated with repeated administration at both the 12 and 16 microgram daily doses.
Finally, the results from the SAD cohort showed the expected effect on renal calcium re-absorption with maintenance of a normal fractional excretion of calcium, which is important to minimize the long-term adverse effects of the disease and its treatment on renal function. As you may be aware, PTH control serum calcium via several mechanisms.
First, it acts to release calcium from the skeleton. Second, PTH facilitates the conversion of 25 hydroxy Vitamin D to 125 dihydroxy Vitamin D, the active form, which in turn acts on the intestines to increase calcium absorption.
Finally, presence of PTH is required to act on the kidneys to reabsorb calcium from the urine into the bloodstream, and decrease re-absorption of phosphate. For patients with hypoparathyroidism, continuous presence of PTH should allow control of urinary calcium.
This is critical given the four fold greater risk of long-term renal disease and the high rates of hospitalization for these patients. In terms of safety, TransCon PTH was generally well tolerated across the likely clinical dose range. We are extremely pleased with the emerging data from our TransCon PTH trial.
We believe that our initial results support our plan to advance directly into the Phase 3 study pending discussions with regulatory authorities. Our third product candidate, TransCon CNP also continues to advance as a potential treatment for achondroplasia and related skeletal disorders.
In December, we completed regulatory submissions in Australia to enable our first in human Phase 1 trial for TransCon CNP, which is expected to begin dosing healthy adult subjects during the second quarter. The trial will evaluate safety, tolerability, and pharmacokinetics with the goal of identifying safe doses for future efficacy trials.
We expect top line data to be available in the fourth quarter of 2018. As you know, there is a high level of interest in development of treatments for achondroplasia from the medical, patient, and regulatory communities.
To this end, FDA is planning to hold an advisory committee meeting to discuss drug developments for the treatment of children with achondroplasia. We look forward to the panel discussion as it will help inform our TransCon CNP program.
We will be interested to hear the views on defining clinically-meaningful outcomes that could help improve patients' lives. 2018 has started off with strong momentum across all three of our rare disease endocrinology programs.
We have a pipeline of products designed to address unmet needs, and we have assembled a very committed and experienced development team. We look forward to achieving our milestones and bringing these product candidates closer to patients during the coming year. Now, Scott will provide a financial update..
Thank you, Jonathan. Turning to our financial results for the full-year ended December 31, 2017, let me review some highlights. We ended 2017 with cash and cash equivalents of €195.4 million on a reported basis.
In February this year, subsequent to the December 31 year-end, we completed a follow-on financing further strengthening our cash position as we advance our pipeline. Net proceeds from the February 2018 financing were approximately $242.5 million, or approximately €196.8 million based on exchange rates as of the date of the financing.
Combined with our year-end cash balance, this financing ensures that Ascendis is well-capitalized to pursue our Vision 2020 to become the leading integrated rare disease company. As of December 31, 2017, the company had 36,984,292 ordinary shares outstanding.
As of today, including the February 2018 financing the company has 41,523,765 ordinary shares outstanding. For the full-year 2017, we reported a net loss of €123.9 million or €3.68 per basic and diluted share compared to a net loss of €68.5 million or €2.58 per basic and diluted share during 2016.
The 2017 loss reflects an unrealized noncash €13.7 million finance expense due to foreign currency exchange fluctuations for the year. Research and development costs for 2017 were €99.6 million compared to €66 million during 2016.
Higher R&D costs in 2017 reflect an increase in manufacturing and clinical costs related to preparation for and execution of the Phase 3 clinical program for TransCon GH, including the heiGHt, fliGHt, and enliGHten trials.
Ongoing development of our proprietary auto-injector for use with TransCon GH, an increase in costs related to the Phase 1 clinical trail and activities related to Phase 3 initiation including manufacturing and device development for TransCon PTH, and preclinical development costs associated with TransCon CNP.
General and administrative expenses for the 2017 year were €13.5 million compared to €11.5 million during 2016. This is primarily due to an increase in G&A personnel. During 2017, we expect an increase in R&D expenses and so we continue to advance our wholly-owned internal pipeline programs and invest in the TransCon technology platform.
R&D expenses will include for TransCon Growth Hormone costs associated with our Phase 3 clinical supply and manufacturing of validation batches which we expect to be used for commercial supply.
Costs associated with the ongoing Phase 3 clinical program including execution of the heiGHt, fliGHt, and enliGHten trials, and costs associated with ongoing development of our proprietary auto-injector for use with TransCon GH.
For TransCon PTH, R&D will include Phase 3 enabling activities including nonclinical talks, manufacturing, regulatory, and device development activities, and the ongoing Phase 1 clinical trial.
And finally for TransCon CNP, R&D will include ongoing Phase 2 enabling activities including nonclinical talks and manufacturing and costs associated with the Phase 1 trial which is expected to dose the first patients in the second quarter this year.
We expect to make meaningful progress on each of our wholly-owned rare disease pipeline candidates in 2018 and sharing new developments with you on all three of our programs over the next 12 months.
Key upcoming milestones include TransCon PTH Phase 1 data from all SAD and MAD cohorts, TransCon CNP Phase 1 data, regulatory discussions and agreement regarding design and initiation of our Phase 3 program of TransCon PTH, and top line data from our heiGHt trial of TransCon GH.
Our goal is to continue to leverage our TransCon technology to create a pipeline of internal proprietary products.
As we disclosed to you during our February 2018 financing, we intend to use a portion of the net proceeds from that financing to apply our algorithm for product innovation to expand our pipeline including potentially into new therapeutic areas. Operator, we are now ready to take questions..
Thank you. [Operator Instructions] Our first question comes from Jim Birchenough with Wells Fargo Securities. Your line is now open..
Well, hi, guys. Congrats on all the progress. A couple of questions, I guess, first, you alluded to it Jonathan, but the heiGHt and fliGHt rollover into enliGHten, could you quantify it. It sounds like there's a pretty decent rate of rollover, but are you able to quantify that for us..
So far every subject who has completed the heiGHt trails has chosen to enroll into enliGHten. Now, we've not provided exact numbers yet but it's been a hundred percent so far, and I expect it to remain very close, if not at 100%..
And then maybe just on TransCon PTH, with a 60-hour half-life is there any possibility of spacing it dosing less than once daily.
And I'm just wondering with once-daily dosing do you expect to achieve an optimal steady state or then this would make any sense to spacing up the dosing further?.
Jim, it's a pretty interesting question. But I think it's mainly going back to the old question, how do we build up optimal adherence to our patient population? And the given [Ph] rule has always been that you'd like to have and the treatment administration that is built on something that the patient really can remember.
And it comes back to daily administration, weekly administration, monthly administration. So therefore even we believe we can develop and the treatment administration that can support perhaps twice weekly injection potentially once-weekly injection.
We think it's important to start with a daily administration because it give us this opportunity to be in a position that we can titrate in an optimal manner the fast and best way to really to get the [indiscernible] treatment that is optimal for the patient.
And then we can discuss, potentially later on, that if you have stabilized the patient we can move then on then once-weekly product opportunities, more like a kind of lifecycle management opportunity. But from that perspective we believe that the daily administration.
And one of the more really, I think, appealing element of our long half-life about 60-hour is that if a patient by any means forget to take the administration just for one day they are in a position that they are not suddenly losing completely the PTH level, but you will have a sliding scale of less and less of PTH [Ph] so you're not sitting suddenly in a situation where you have an hypocalcemic episode..
And maybe one last question if you'll allow me. It strikes me that for the TransCon PTH program that you're differentiation versus things like Natpara are on the urinary calcium side. But that's also a differentiator from calcium and vitamin D supplementation which is more broadly used.
So the question is do you think in a Phase 3 you'd incorporate an arm where you have vitamin and calcium supplementation..
So, another good question. So we absolutely will compare ourselves to the first line therapy, which is calcium and vitamin D. And you're right; lack of control of urinary calcium is a major problem there as well as for Natpara.
So we will clearly incorporate control of urinary calcium as an important component of our endpoints because we feel it's a very important aspect of the disease that's not been well addressed so far..
Just to add in, Jim, we also believe that if we go away on secondary point, secondary point could be more a normalization of [indiscernible], it could be -- also be which some day could mean that you have a much more healthy bone metabolism.
And I also believe that other element where we can see a benefit of the profile we provided and having PTH over in the physiological level for 24 hours a day.
But we're quite sure the easiest and perhaps the most important one is definitely the urinary calcium, and that as Jonathan said, it's really one where we see a huge differentiation to all standard of care treatment, including Natpar..
Great. Well, thanks for taking the questions..
Thank you. Our next question comes from Jessica Fye with JP Morgan. Your line is now open..
Great. Thanks for taking my question. Can you talk about your estimate for the standard deviation in height velocity in the Phase 3 growth hormone trial, or maybe just what it's been in other recent Phase 3s? And then sticking with growth hormone, you reiterate the timeline for database log for the clinical program in 3Q '19.
Beyond that kind of clinical data, what are the remaining gating factors to think about that you would need to knock out prior to filing? Is it accruing more long-term experience, is it manufacturing? And can you also remind me of where we stand in terms of incorporating the auto-injector into the growth hormone clinical program? Thank you..
Hi, Jess, Jonathan here. So for the standard deviations, the exact numbers I don't know that are critical, but I'll tell you what our approach was. So our approach was to take our own experience from Phase 2, take the standard deviations that we actually saw in our hands, realized that we were expanding from 40-some odd sites to about 90 sites.
And when you do that the standard deviation typically expands, enlarges, worsens. And then we looked at the standard deviation from other published studies and kind of just took all of that into account. And I tend to be relatively conservative when I power studies.
So I looked at standard deviations that were on the conservative side in coming up with our numbers. And that gave us a number of 150 subjects. And then of course, even from there we over-recruited, so we went beyond that. So, that's kind of the general approach that I have taken in designing the heiGHt trial with the team here.
And for the auto-injector question, we are going to incorporate the auto-injector into the enliGHten trial some time early next year. So patients, when they're in the extension study, will begin using the auto-injector at some sites..
So, Jess, going back to your last of your question, just to clarify one thing, we expect, and this is our plan, to have the auto-injector ready for launch. So it would be part of our filing document.
We think is an essential part of providing an optimal treatment for the patient with growth hormone deficiency that also be having the auto-injector available. Related to the filing date, this is something we have been executing on for long time now.
We have three different elements that we -- I try to group it in three different element just to be quite sure that it's more in small packets. One packet is related to the preclinical safety. It basic done. We're starting and writing that up now, finalizing everything we report on.
What Jonathan just disclosed was in Q3 next year we will have all clinical data that is necessary for supporting a filing in both the U.S. and in EMEA ready. The last part of that is validation batches.
And you can see from [indiscernible], we already are executing on the validation batches, because it will be part of our commercial production that will be out-coming of the patients. We still logging the last timeline of the last part of the validation batches.
And then soon as they are really locked down to days and months we can give you the basic -- the date for the filing. But we're also feeling that we want to be very transparent, and we want to keep milestones, and being quite sure we can live up to them as -- we have not really locked down the last part of that manufacturing steps.
I think it's much better that we will come to you and saying this will be our filing date..
Okay, understood.
And then on CNP, just as we anticipate that data in the fourth quarter, can you talk about the extent to which we can feel comfortable reading across from the PK data for PTH, for example, to that program in terms of your ability to replicate what you're seeing pre-clinically? And are there any biomarkers that you can evaluate in the healthy volunteers for the CNP product?.
I can take the first part of it, and then move it over to Jonathan to take the second part of the question. First part is that what we have seen for all product opportunities that has been developed with TransCon technology are pretty unique and really great translation from preclinical data-specific primus data into humans.
That is not only for PTH, we have seen it for all our product opportunities. Yes, sure it give us -- I'm confident that we hope there will be a great translation. We have at least the [indiscernible] with us, not against us, because we have seen it every time that can be coming up product-specific elements that we have never considered.
We think we have really started and analyzed the fundamentals in each single product opportunity to really deep level that we -- feeling that we think that we have a great chance to see the same translation that we saw with PTH and also for CNP.
Jonathan will address what we're trying to get out of that trial and also what we expect to see of [indiscernible]..
So we'll certainly get a full safety profile from the healthy volunteers, we get a tolerability profile, we will get the infusion-like profile that we expect as we saw with PTH as well to see in that study. In terms of biomarkers, there are some biomarkers such as Cyclic GMP that we can measure both in urine and serum.
There is also some experimental biomarkers of bone metabolism that we are considering as well.
And then finally, I would say that if we don't see a drop in blood pressure which we are not expecting to see and we have not seen pre-clinically, that would allow us to push the dose to higher levels where we might really optimize our efficacy signals in those children..
Great, thank you..
Thank you. [Operator Instructions]Our next question comes from Alethia Young with Credit Suisse. Your line is now open..
Hi, thanks for taking my question. This is Derrick [Ph] on for Alethia. Congrats on all the progress for the quarter. I guess I have two questions from me if I may.
My first one is about the FDA advisory meeting for achondroplasia, can you provide some color and your thoughts about your expectation, the different possible outcome from the meeting, and how those factor your TransCon CNP development plans?.
Sure. So, thanks for that question.
We are really looking forward to this, and we think it's a great sign that FDA has called for this meeting, because in their briefing materials, it looks as if they are really, really focused on what are clinically meaningful endpoints in these children, and what kinds of study designs are required to establish that.
And that has long been our passion as well. We really want to make a difference in this disease state, and we are really focused on what are the clinically meaningful endpoints. We have our own ideas about that, and we certainly are going to follow with great interest as the panel discusses that.
No matter what happens, it will clearly inform our plans and we think they are likely on the right track..
We also believe that the timing is perfect for us. We are in a position now where we're really defining how we really will develop our TransCon CNP in the late-stage clinical development, and getting this kind of input is the right timing because we can integrate it into our plans..
And I think kind of the obvious question is how important is heiGHt if at all? So, you might grow more, but does that really correlate with the real unmet need in this disease state? So we look forward to that discussion, we certainly have our own views on that topic..
Okay, thanks. The other question on the PTH part, can you walk us through how the calcium excretion is calculated? I know there is a chart, you see percentage of 1% to 2%; you can maintain that level.
I'm wondering what is the expectation for that number and how is the data compared to that expectation?.
Sure. So, fractional excretion of calcium is just that it's what percent of calcium is delivered to your kidney is actually excreted and how much is reabsorbed. And that is a formula that you can just look up, but it involves measurement of urine and serum creatinine, and then making a ratio of that and urine and serum, serum calcium levels.
So, those four components, you plug into an equation and you get the fractional excretion of calcium. Now, normal fractional excretion of calcium is about 1% to 2%.
And I think the really critical part to understand in our poster, and it explains what we are seeing in our data is really that the figure in our poster that shows that if you were to clamp a calcium level of 10.3, and this has been done in previous literature, and you look at the fractional excretion of calcium in normal volunteers, it goes up to that six to seven and that is because in normal volunteers where you falsely elevate their calcium levels to 10.3, you completely suppress their own endogenous PTH.
So, those healthy volunteers have no PTH presence and a hypercalcemic blood level. What happens then is your calcium gets dumped by the kidney, because there is no PTH present or reabsorbed.
Now, you turn to our study, and when we raised the calcium levels with PTH level of 100 micrograms single dose to 10.5 or more similar to that other published study I told you about, you would expect fractional excretion of calcium to go up to six to seven, but in fact it remained normal, because in our study we had continuous pressure of PTH at the kidney.
In fact, this is just a wonderful representation of how important it is to have PTH present 24/7. In the presence of PTH you don't dump calcium even when your calcium level is abnormally high..
Okay, that's helpful. Thank you..
Does that answer your question?.
Yes, thank you..
Okay, you're welcome..
Thank you. As I am showing no further questions in queue, I would like to conclude today's conference. Thank you everyone very much for their participation, and you may all disconnect. Have a wonderful day..
Thank you everyone. See you. Bye-bye..