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Ascendis Pharma A/SÂ (ASND -0.75%)
Q2Â 2019 Earnings Call
Aug 28, 2019, 4:30 p.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
Operator
Good day, ladies and gentlemen, and welcome to the Q2 2019 Ascendis Pharma Earnings Conference Call. [Operator Instructions]
I would now like to introduce your host for today's conference, Mr Scott Smith, Senior Vice President and Chief Financial Officer of Ascendis Pharma, Mr. Smith, you may begin.
Scott T. Smith -- Senior Vice President, Chief Financial Officer
Thank you, operator. Thank you everyone for joining our second quarter 2019 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 Office; Tom Larsen, Chief Commercial Officer; and Juha Punnonen, Head of Oncology.
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 are not limited to our progress on our pipeline candidates and our expectations with respect to their continued progress statements regarding our strategic plans our goals regarding our clinical pipeline, 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 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 on April 3, 2019. Please note that our TransCon product candidates are investigational product candidates and are not approved for commercial use. The safety and effectiveness of any TransCon product candidates have not yet been established. None of the statements made on the conference call regarding our TransCon product candidates shall be viewed as promotional.
On today's call we will discuss our second quarter 2019 financial results and provide a business update. Following some prepared remarks, we will then open up the call to questions. I will now turn the call over to Jan Mickelson, our President and Chief Executive Officer. Jan?
Jan Moller Mikkelsen -- President and Chief Executive Officer
Thanks, Scott. Today, I would like to focus on how our TransCon Growth Hormone program is enabling us to build Ascendis as a global leading biopharma company. This year, we achieved major milestones with the -- with the completion of our two Phase III trials, the heiGHt and fliGHt Trials for TransCon Growth Hormone, our once-weekly growth hormone therapy in development for pediatric growth hormone deficiency.
For untreated subject, we reported data showing TransCon Growth Hormone demonstrated superior efficacy, while maintaining comparable safety and tolerability to a daily growth hormone. We also showed it was safe and well tolerated it's subjects, previously treated with daily growth hormone and children younger than three years of age. Based on this finding we expect TransCon Growth Hormone to be raising the bar and setting a new standard in the treatment of growth hormone deficiency.
With both Phase III trials now completed and database is locked, we are now preparing for BLA filing in the first half of 2020 and MAA filing in the second half of 2020. Two items, need to be finalized for these filing. First, this quarter we expect to complete our robust, long-term safety package to be included in the filing. This data set has been agreed upon with input from regulatory authorities in the US and Europe. We are on track to have the last subject out this quarter for the long-term safety data set consisting of around 300 subjects treated for at least six months, 120 subject for 12 months and 45 subject for 24 months.
Second, in the coming months, we will complete the process validation activities and the associated qualification reports. With these two last pieces on track and the successful introduction of the auto-injector in the enliGHten Trial, we are now taking the opportunity to step back and further analyze all our clinical resource from an integrated holistic view across both our Phase II and III trails. Our key learnings are, first, TransCon Growth Hormone demonstrated a safety profile comparable to that of a daily growth hormone. Second, TransCon Growth Hormone demonstrated superior efficacy to a daily growth hormone in the heiGHt trial. With a PK profile off released growth hormone that may indicate more efficient utilization by target tissue throughout the entire body. Next, TransCon Growth Hormone data showed a predictable response to dose titration, which may provide physician with the flexibility needed to successfully dose titrate each patient to the desire clinical outcome at all stages in the treatment of growth hormone deficiency.
Last, TransCon Growth Hormone data suggest the same mode of action as daily growth hormone by preserving that by a logical balance between the direct effect of growth hormone and the indirect effect of IGF-1 in target tissue. These results highlight the important that a long-acting growth hormone must have the same mode of action as daily growth hormone. By releasing unmodified growth hormone, the same molecule as daily growth hormone and it [Indecipherable] growth hormone.
TransCon technology is uniquely designed to leverage both the direct and indirect effect of growth hormone in the same balanced way as daily growth hormone has for decades. Indeed it is the combination of the direct and indirect effects of growth hormone, which are the key to support the body's overall endocrine health. This includes not only heiGHt, but also body composition, metabolic and cardiovascular health and even mental well being. With TransCon Growth Hormone we are not changing this priority. We are simply replacing what the body is missing unmodified human growth hormone. In our Vision 3x3, the goal is to achieve sustainable growth through multiple approaches. Two important strategic driver for sustainable growth for our endocrinology rare disease pipeline are global clinical reach and label expansion programs.
Let me start with the global clinical reach. Recently, I traveled to China to visit the leadership of VISEN Pharmaceuticals. Our strategic collaboration form with an investor syndicate nearly one year ago. After discussion with the team leading the development of TransCon Growth Hormone in China. I left confident that through VISEN, we have the local expertise and affirmed plan for the development and commercialization of our rare disease pipeline in Greater China.
In addition, as Ascendis is also in an unique position, where we have the possibility of conducting clinical trials for our rare disease endocrinology pipeline in China through VISEN, that potentially could accelerate our development timelines in the Western world. Why is the Asian region important for Ascentis? As you may know, China, India are now the second and the third largest pharmaceutical market in the world. Many of the fastest growing pharmaceutical markets are also in Asia. Reinforcing the importance of this region in our recent 3x3 strategy to create sustainable long-term growth through multiple approaches.
In China, VISEN has been working on the development and commercialization plans for TransCon Growth Hormone. The Center for Drug Evaluation or CDE in China agreed that we can fully leverage our existing non-clinical package and have no need to conduct and it look we can study with Chinese subject. Just recently an IND was filed for Phase III trials for pediatric growth hormone deficiency with CDE and is under technical review. This Phase III trial in China for TransCon Growth Hormone is expected to enroll around 75 pediatric subject at VISEN expect to begin the trial this year.
In Japan, we have agreed with the Pharmaceuticals and Medical Device Agency or PMDA our next step with the goal of initiating a Phase III trial in 2020. PMDA agreed that we can fully leverage our existing non-clinical data package and we have agreed to conduct an -- operating study to begin this year. In parallel, we are actively working to develop the Phase III protocol including around 40 pediatric subjects, expected to be initiated next year.
In South Korea, we sought advice from the Ministry of Food and Drug Safety on next date. They also agreed that we can fully leverage our existing non-clinical data package and move directly toward regulatory submission and marketing application without full clinical trials. By establishing a global reach across our program, we believe that we would be able to build and maintain a competitive events as we are building a growing biopharma company.
Label expansion is another important element in our Vision 3x3 strategy for creating sustainable long-term growth for rare disease endocrinology pipeline. For TransCon Growth Hormone, the first indication for label expansion will be adult growth hormone deficiency. For this indication, we expect to combine both the label expansion and global clinical reach in one single program. We expect to initiate a a global clinical trial next year for subjects with adult growth hormone deficiency incorporating clinical sites in the US, Europe and selected countries in Asia.
For commercialization of our rare disease endocrinology pipeline, we are dedicated to bring our product opportunities all the way to patients as quickly and as broadly as possible. By building a pipeline of a leased three independent high-value product opportunities in rare disease endocrinology, we believe that we are creating the levers synergy economy of scale needed for our own commercialization. We have already started this process in areas like North America and European countries where we are driving toward commercialization, the filing of our first regulatory submission for TransCon Growth Hormone next year.
The promise of our TransCon platform is clear. The TransCon Growth Hormone results have validated our ability to move from an innovative idea, all the way to a successful Phase III development program of an unique product candidate. This validation of the TransCon platform give us increased confidence in both our rare disease endocrinology pipeline programs that we will also set a new standard with TransCon PTH and TransCon CNP. And the broad potential of the development of product candidate withi TransCon technologies in other therapeutic areas such as oncology. With our progress this quarter, we are one step closer to establishing a broad global reach for TransCon products and one step closer toward achieving our recent 3x3 goals.
Let me now turn the call over to Scott for financial update.
Scott T. Smith -- Senior Vice President, Chief Financial Officer
Thanks Jan. Turning to our financial results for the three months ended June 30, 2019, let me review some highlights. For the second quarter, we reported a net loss of EUR58.9 million or EUR1.25 per basic in diluted share compared to a net loss of EUR22.8 million or EUR0.55 per basic and diluted share during the same period in 2018. The second quarter 2019 net loss includes an unrealized non-cash loss of EUR8.2 million compared to an unrealized non-cash gain of EUR21.3 million in the 2018 quarter due to foreign currency exchange rate fluctuations.
Research and development costs for the second quarter were EUR43.8 million compared to EUR40.2 million during the same period in 2018. Higher R&D costs during the 2019 quarter reflect increased personnel and infrastructure costs due to growth in headcount to support development of our product candidates. For TransCon Growth Hormone, costs were lower primarily due to a decline in manufacturing and clinical trial costs following the completion of our Phase III heiGHt Trial.
For TransCon PTH, costs were slightly lower, primarily due to a decline in costs for pre-clinical research and constant develop our pen [Phonetic] device, which were partially offset by higher costs associated with our Phase II clinical trial. For TransCon [Indecipherable] the costs were slightly higher, primarily due to an increase in manufacturing costs and clinical trial costs related to our achieve study and accomplished trial, which were partially offset by lower pre-clinical costs. Other R&D costs were higher, primarily due to activities to support our oncology therapeutic area. As a reminder, our R&D expenses, including manufacturing-related expenses vary from quarter-to-quarter reflecting timing of ongoing development activities.
General and administrative expenses for the second quarter of 2019 were EUR11 million compared to EUR5.2 million during the 2018 period. These higher costs primarily reflected increase in personnel and site costs as well as costs of building out commercial capabilities. We ended the second quarter with cash and cash equivalents of EUR690.4 million and 47,545,204 ordinary shares outstanding. As a reminder, our quarterly ending cash balance may be impacted by a combination of items, including exchange rate in working capital fluctuations, which this quarter led to a net positive impact on the ending cash balance. During the quarter we continue to execute on our Vision 3x3 strategic road map and our recent initiation of the Phase II accomplished trial for TransCon CNP.
Looking forward over the near term, we plan to complete long-term follow-up for TransCon hGH this fall as agreed to with FDA and EMA as we progress toward a BLA filing in the first half of next year. Continued growth of our endocrinology rare disease pipeline through label expansion of TransCon hGH into adult GHD and initiation of the Phase III trial of TransCon hGH in China through VISEN Pharmaceuticals. Report Phase II TransCon PTH data by year end continue executing on the TransCon CNP accomplished trial as we march toward discovering an effective dose in 2020. Advance oncology product candidates toward first IND or similar filing in 2020 and continue to expand our global reach for our endocrinology rare disease pipeline.
Operator, we are now ready to take questions.
Questions and Answers:
Operator
[Operator Instructions] Our first question comes from Josh Schimmer with Evercore. You may proceed with your question.
Josh Schimmer -- Evercore -- Analyst
Hey, thanks for the updates and for taking the question. As we approach the Phase II TransCon PTH data. I was hoping maybe you can help frame the unmet need for us in terms of the number of patients in the US with hypoparathyroidism, the general split between severe hypo PTH patients and perhaps more mild-to-moderate and we're Natpara from your understanding has been able to make inroads in penetrating into the market and where it hasn't and the extent to which you think TransCon PTH can succeed where Natpara has not? Thanks so much.
Jan Moller Mikkelsen -- President and Chief Executive Officer
Thanks just as always a good question. So what we actually stated in our slide deck, it's our [Indecipherable] we gave an overview about the patient group that we would like to someway cover in our Phase III study. And if you look on the numbers we get from the US, it was about from 70,000 to 110,000 in the US. In Europe, it was about 90,000 to 200,000, Japan for about 25,000 to 32,000 and South Korea pitching around around 12,000. So you can see in average it is more than 200,000 patients that we actually believe our global Phase III program really will have the opportunity to really cover. And to the question you are reflecting is how large of this proportion of patients will we actually would expect to treat and I could always turn it back to what I call the real disease. If I look on the condition, if I look on how this patient group are basic are not really can't function, all the, what I call the short-term symptoms, which I think is very well described in our survey in -- from our research team, but also what is really the long-term complications, just what you see the assets rate of [Indecipherable] complication 5-fold and other things. So we're really dealing with what I called really a severe -- more than 35% cannot really managed to keep a job. So we're really talking about both short-term symptom and long-term complications.
And to address part of your last question before I come to the final conclusion is, I actually think you cannot compare TransCon PTH to Natpara because you're comparing two different compound with complete two different clinical profile. What we want to do in TransCon PTH is basic develop a true replacement therapy. And what do it mean with that? I mean that we get back to the body exactly as they need it molecule identical molecules they really need. That is the first requirement of a true-replacement therapy.
But I think where we have and will be highly differentiated compared to Natpara is in the second part of what I think is exactly as important as a true replacement therapy is provide it back in the right physiological way. And what we want to do and this is what I think that is really clear agreement both to regulatory agencies to just reading the literature related to treatment of the disease is that you need to give it back in the physiological level where you have PTAs in the physiological levels 24 hours, 7 days at a week.
So therefore when I see what that really results by having a true replacement therapy, it was basic mean that you basically can remove all the supplements and take them to a level where you basically see the same amount of supplements being given as you see in a normal population, you will normalize urinary calcium, you will normalize phosphate, you will basic recall the normal life. To date, how do we do that? You give them infusion pump on children patient that is. So I personally believe that the majority of this patients should be treated with TransCon PTH that have hypothyroidism. Would that happen? Definitely not. That's not all of them will be treated.
But I believe that a large portion of them and it could be between 30% to 60% of these patients are suffering so much that just from a pharmaco-economic calculation and then seeing the patient need there should be in treatment. That was a long answer for this short question.
Josh Schimmer -- Evercore -- Analyst
Great, thank you so much for the comprehensive answer.
Operator
Thank you. Our next question comes from Tazeen Ahmad. You may proceed with your question.
Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst
Hi, good afternoon and thanks for taking my questions. Yeah, I'm sorry if I missed this in the your prepared remarks, but when you submit your application for GHD next year, is it your anticipation that there will be an outcome for it?
Jan Moller Mikkelsen -- President and Chief Executive Officer
As you know Tazeen, this is not really my decision. We are trying to some way to position us in the way we write the BLA that I think we are trying to take any kind of theoretical consideration that we can think about and build it into the PLA so be trying to be proactive when we describe this. For example, the analysis we did related to the balance the team, the indirect and direct effect of growth hormone was actually some part of that effort to really show that we are the only long-acting growth hormone that it will have seen, where we basic are keeping the same balance with team direct and indirect effect.
And I actually think this is some of the thing. So when you go back to our slide they can see the key learnings from our TransCon trials is basic some, some of the summary that is part of the BLA statement that somebody will be giving the fundamental really to have a strong position. You can ask me on a personal level, do I believe? There is a reason in the data sheet that should be an outcome, I don't believe that and we can also ask Jonathan, our CMO and hear what he will answer this question.
Jonathan A. Leff -- Senior Vice President, Chief Medical Officer
I will very much agree. I think the data that we've generated to-date is really unambiguous and if and when it's ambiguous and not quite clear that leads to Advisory Committee. So our hope is that we would not have an advisory committee. Of course if there is one, we will be prepared.
Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst
Okay, great. And then another question also on GHD. You're planning on applying in the US in the first half of next year and then Europe in the second half. Is there any difference in what each of the agencies is asking for in terms of data that you would need to submit?
Jan Moller Mikkelsen -- President and Chief Executive Officer
No, this basically is exactly the same target that will be filed in place [Phonetic]. I can think that has been, I never seen such a great alignment of the team, all the agencies, both in US and Europe. That basic have been noticed from the team what we will provide updates packet.
Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst
Okay, great, thanks.
Operator
Thank you. And our next question comes from Jessica Fye with JPMorgan. You may proceed with your question.
Jessica Fye -- JPMorgan -- Analyst
Great. Good afternoon, guys. Thanks for taking my questions. I had a few on PTH. I'm going to say them all once. First, can you help us think about what the typical calcium dose might be for patients enrolling in the path forward trial, acknowledging the 400 milligram BID minimum? And where do you think that might end up after optimization of supplements to get calcium into the normal range?
Second, can you maybe just set expectations for that Phase II dataset around whether investors should expect to see statistical significance on the primary endpoint versus just clear separation? And lastly, you sort of related to that, is it possible that the highest dose might not end up with the best response rate should it push patients above the normal range on serum calcium?
Jan Moller Mikkelsen -- President and Chief Executive Officer
I think Jonathan will take the first question and I will continue.
Jonathan A. Leff -- Senior Vice President, Chief Medical Officer
Okay. So we would expect the patients that are in the path Forward trial would typically require 1000 milligrams of calcium or more. Some of these patients, as you know sometimes require 2000 or even more, but somewhat in that range. And after treatment with TransCon PTH even after a short period of four weeks, we would expect the great majority of those to taper off calcium to the degree of -- well taper off vitamin D for sure. And most of them will taper off calcium, except that all of us require about 500 milligrams to 700 milligrams of calcium in our diet. So many of them might end up on those low doses of calcium, which would be typical of all of us.
Jan Moller Mikkelsen -- President and Chief Executive Officer
So going to back, how we have designed our Phase II trial. And, often when we talk about our Phase II trial, at least from the centers view, we try to conduct a Phase II trial in such a manner that we basically can derisk it before we move into the Phase III trial. This is where we actually like to be dose [Phonetic] where we were with the TransCon Growth Hormone. Some saw there was a big surprise for basic what we had in our Phase II trial got repeated in our Phase III trial. This is why we someway are allocating the same endpoints that we want to use in Phase III trial, also into our Phase II trial. The question you're asking is, are were powered sufficient enough to basic to hit the statistic significant in our Phase II trial? And often we are in a position that we first really can't answer this, when we haven't done it, but what we are getting for getting the statistic power to really to be in position to design the Phase III trial, so we can have high level of insurance that we will hit the statistic power in our Phase III trial. So therefore the goal for the Phase II trial is basic not to hit the statistic power. If we do it, I don't know, but this is not really recovered [Phonetic] on it, but I do not know. The second question, you have is, yes, you could be right, it could be and I think it could be likely that the highest dose, the 21-microgram dose will be too high dose as a starting dose.
But this is how we're actually exploring it, it could be 15 is optimal starting dose. We don't believe that the optimal starting dose will be much lower than 15 because we know in average there will be a use of PTA when you use infusion pump which was about 15 level. So therefore, we believe that it will be highly likely -- it will be under that. So therefore potential of the 15 or 18 could be the optimal starting dose and the 21 could be too high.
And what we basic will seen that is there would be some patients that would be hypocalcemic, but just showing that is a highly saturatable compound and we have the right property to get single patient adjusted to the right level dependent on the severity of the disease and what is optimal calcium limit that is for this patient.
Jessica Fye -- JPMorgan -- Analyst
Okay, great. Thank you. And I just have one more if I could on growth hormone. I appreciate the comment on manufacturing earlier in the call. Can you please just elaborate a little bit on that topic and ideally share a little more detail to help us understand the remaining steps that need to take place for you to file the BLA and also to launch TransCon Growth Hormone?
Jan Moller Mikkelsen -- President and Chief Executive Officer
Yeah. So, basic the two missing part. We have now first part is the last patient out was having this quarter related to locking the safety database that we have proposed and agreed with the authorities. And that is happening this quarter. The second part is that we, in the coming months, we were finalizing the three independent validation batches and then they are finalized, we need to be quite sure that we are getting all the reports, all the quality statement is being made. And then the basic -- can compile the last part of the BLA. It's not like we have been writing the BLA for the last 10-12 months now and people are extremely resource demanding and getting all this believe really written and so we basic have a rolling way to do it and we will be in a position that the two largest [Phonetic] pieces, is the two largest partly writing together as last.
Jessica Fye -- JPMorgan -- Analyst
Okay, thank you.
Operator
Thank you. Our next question comes from Michelle Gilson with Canaccord Genuity. You may proceed with your question.
Michelle Gilson -- Canaccord Genuity -- Analyst
Hi, thank you for taking my question. I wanted to go back to a comment that you made Jan on regulators recognizing TransCon PTH as a physiologic PDH replacement. Can you just talk a little bit about what you will be looking for as far as TransCon PTH's profile? What you need to show and either in both the Phase II and Phase III to show that TransCon PTH converged an advantage over supplements perhaps?
Jan Moller Mikkelsen -- President and Chief Executive Officer
I actually think that the -- So Michelle, this is a great question because this goes back to the fundamental of this product opportunity. The fundamental is that, how do you have the optimal treatment received today is either by Natpara, either by [Indecipherable], by really insulin pump that provide a steady-state level of PTH 24 hours, 7 days a week. And what we showed in the Phase I setting, we showed that we basic and -- not only the PK, but all the expected PD effect of a continuous infusion in healthy volunteers.
What we're doing now? We're basically moving up and showing that in our Phase II trial where we will do it not in healthy volunteers, but in adult patients with hypoparathyroidism, that is what we're doing in there. What we can see In this stage, I think we receive exactly the same thing I expect to see with an infusion pump. We will see the basic can't be [Phonetic] in a position, we can withdraw all the supplements, which you're basically doing on day one for the patient when you start the infusion pump. Also believe we can see exactly the same thing that you see with an infusion pump in patients with hypoparathyroidism is that you see a normalization of urinary calcium and that is indicating exactly the physiological effect you expect to see and with having just a person that providing the normal physiological PTH level 24 hours, 7 days a week.
So when I go back and say, yes, we were not only see it highly differentiated against standard of care, but we also can already see it highly differentiated against a product like Natpara, which basic only 50% of them minus to which will all the activated vitamin D, only 25% minus to with all of the calcium supplement. And this we already can establish on a Phase II trial.
Michelle Gilson -- Canaccord Genuity -- Analyst
I guess, in terms of what regulators are looking for in terms of, I guess, showing how TransCon PTH may have an effect on renal complications and quality of life bone complications, do you think those things can be elucidated in the Phase III study?
Jan Moller Mikkelsen -- President and Chief Executive Officer
Exiting [Phonetic] the clinical development, people have really designed it very well because what is happening with these 40 patients, they're going on to extension study. In this extension study, you will have the opportunity really to see how we address long-term complications. So you're 100% right. What we basically will see in the -- this study, we can see some kind of symptoms, the short-term symptom, we can see effect on them. What we can see on long-term, we will see in an extension study.
And Jonathan, you can see -- you have developed a great patient reported outcome, which are really will be unique to really -- to [Indecipherable] excited with the benefit we see from the therapy.
Jonathan A. Leff -- Senior Vice President, Chief Medical Officer
Yeah. I mean, I don't have a lot to add. In the short-term Phase III studies, the goal is to manage calcium to manage -- both in the blood and in the urine. And to greatly reduce or completely reduce vitamin D and calcium, that's a practical outcome you can show in a short-term Phase III trial. And for the longer term, as Jan said, we're developing the questionnaires that will inform us on all of the long-term complications.
Michelle Gilson -- Canaccord Genuity -- Analyst
Okay. Thank you so much for taking my questions.
Operator
Thank you. Our next question comes from Jim Birchenough with Wells Fargo. You may proceed with your question.
Jim Birchenough -- Wells Fargo Securities -- Analyst
Yeah. Hi, guys. Congrats on all the progress. A few questions. Maybe just starting with TransCon Growth Hormone. Jan, you did very good at predicting the positive outcome you've had with TransCon Growth Hormone and the benefits of an unmodified growth hormone. Could you maybe speak to the other side on the risk of a modified growth hormone and maybe in the context of OPKO data we're going to get later this year? And how much of a risk do you see that data being? And how predictive do you think the biology of a modified growth hormone will be in them being able to match what you've done? And maybe what we should take about as we look at their data?
Jan Moller Mikkelsen -- President and Chief Executive Officer
When we analyzed [Technical Issues] our product -- our long-acting growth hormone, we analyzed what is really the consequence of using a molecule enlargement [Phonetic] principle exactly as OPKO do, and basically, it is that, instead of having at the right balance between indirect effect and direct effect, you're basically eliminating a large part of the direct effect. And you saw that very, very, very clearly in the OPKO trial in Phase III in adult growth hormone deficiency, because there you have TransCon [Phonetic] effect as the primary endpoint. TransCon effect the mode of action is that you need basic to have the direct effect to see this benefit in growth hormone treatment. So when I go back and seeing and starting with the Phase III trial, I look in there product opportunity, what we see and that basic phase in the Phase III trial an adult growth hormone deficiency.
So from a theoretical perspective, from Phase III data, we know already now they are in a position that they don't have the same benefit that you really would have on what I call the integrated effect of growth hormone treatment ensuring that you're getting the right body composition, the cardiovascular effect, the mental [Phonetic] effect and also other things that you expect to see in a growth hormone treatment.
Going then to the specific trial, and what you will see on the primary endpoint is high velocity. Potentially, and I think they have a fair thing [Phonetic] to be non-inferior to daily growth hormone. But who really cares honestly. Because you already have proven that you cannot get the integrated effect on all the effect you want to see in an growth hormone treatment. The other part that you should ask as a question. We need to disclose everything from BMI, we need to disclose all the body composition effect that you also want to see. We also need to show that you are in a position that they really titrate up to the relevant benchmark for them in a US market and that is not what they're comparing themselves to now the 0.24 milligram per kilo per week because this is what they're comparing with our European [Phonetic] dose.
They need to in someway convince us. Can you also get the expected effect compared to a US dose? Which are 0.30 to 0.35 and they selected the highest Phase II data -- Phase II dose in their Phase II trial, so they have no data that suggests that anyone can do it, and I think it's really highly doubtful that can drive and mainly IGF-1 driven growth effect up to that effect. And then you have all the effects some are typical, we start to see like [Indecipherable] when you have something high growth hormone activity together with this indirect or lack of direct effect.
Jim Birchenough -- Wells Fargo Securities -- Analyst
That's very helpful, Jan. And then maybe just on the PTH program, just in terms of the protocol for reduction in calcium and vitamin D supplementation, how much, and you have prescribed, is the protocol? Is there some discretion for investigators, is there any risk that some physicians or investigators won't dose titrate down the calcium and vitamin D as aggressively as others. If you could just speak to that aspect of the trial?
Jan Moller Mikkelsen -- President and Chief Executive Officer
Jonathan, will you?
Jonathan A. Leff -- Senior Vice President, Chief Medical Officer
Yeah. Hey, Jim. It's very prescribed in the protocol. There is a very specific algorithm, there's a chart based on the serum calcium level, they're instructed to reduce. So I think there is very little risk that they will not reduce. There's a little bit of discretion into how fast and whether they reduce the vitamin D or the calcium, but by and large, it's pretty well prescribed in the protocol.
Jim Birchenough -- Wells Fargo Securities -- Analyst
Great. And maybe just finally on CNP, your Phase IIs have been higher are designed to be highly derisking in approaching Phase III as was the case with TransCon Growth Hormone. What are you looking for, in Phase II results for CNP in achondroplasia? What would be a good result that you think would be derisking for the subsequent Phase III?
Jan Moller Mikkelsen -- President and Chief Executive Officer
The first thing is, always, when we are having a pediatric Phase II is safety. We need to show that we have a safe compound all what we have seen in all preclinical more of what we are seeing in our dose acceleration study in healthy volunteers is, extremely safe product. We have not seen basic anything. So really from that perspective, we're feeling really, really on a safe ground. No cardiovascular risk, not in BFC. What we believe we can see in our Phase II trial in children with achondroplasia is we will start to see the efficacy. And the efficacy we want to see and ultimate goal [Private] of TransCon CNP is to do a normalization of the pathway between the hyperactive FGR3 [Phonetic] and CNP. And we do that by selecting in [Indecipherable] of the signal downstream of the activated FGR3 pathway.
And I believe and what we have seen in animal models and what we have seen from other places is this is really possible to basic -- to do a yin and yang normalization of this two pathway. What dose we need to have to achieve that, that is what we want to identify in our Phase II trial and I actually think that will not be one single dose, I think you will see the same thing that you see a lot of, it was doing, density in the disease, you see some mild, some are more in the middle and moderate and some are really severe and I have to believe you, basic we'll see that for some patient paths we need to get the more CNP than other patient. So but what I hope to see on a fixed-dose basis is that we can measure, really which we are doing as the primary endpoint. High velocity as a way to see the effect of CNP and I expect that we will be there meaningful and by meaningful, I mean, is not just one to two centimeter, because you kind of already achieved that partly by giving growth hormone treatment in achondroplasia to date. We're meaning that what we see, for example, in the beginning of growth hormone treatment moving up to an eight centimeters or some that range. I actually think we have huge ambition for this product, because I actually believe we have the tools by continuous exposure of CNP really to normalize this pathway.
Operator
Thank you. Our next question comes from Tiago Fauth with Credit Suisse. You may proceed with your question.
Tiago Fauth -- Credit Suisse -- Analyst
Hi. Thanks for taking the question. So just a follow-up on the CNP. So in terms of news flow from the Phase II, have you guys established a plan for any interim data releases. What are we going to see, when is the first data point that we might see there and are we planning on measuring disclosing any marker data to help establish that profile and perhaps it's a follow up. Beyond the preclinical data, what is the evidence in humans, perhaps if there is any that CNP may lead to that outsized growth relative to perhaps to shorter half life CNP alternatives that are in clinic right now? Thanks.
Jan Moller Mikkelsen -- President and Chief Executive Officer
Hey, that's a lot good question related to the underlying signs and priority [Phonetic] with CNP. And I actually think that CNP, even if we have known the molecule for 20 years, it's really, really developing here. I just found that people are now to do genetic testing about CNP molecule mutation and they are active finding in some mutation in the CNP molecule itself that have major effect on what I call, that the entire growth.
And so there is no doubt CNP is potentially one of the most powerful hormone that ever have been identified with [Indecipherable] growth. So going back to some of the question, because there were like a lot of questions here. One of the thing was related to biomarkers, yes, we are reading [Phonetic] different kind of biomarkers to data is not really any great biomarker and its definitely [Phonetic] simply CNP is not really a biomarker for efficacy and the growth rate is more mainly an effect on the cardiovascular system and nothing to do with what you see in the growth rate. That is different quality in markers that can be evaluated and the evaluating also different biomarkers. And this is where we need to have that associated what are called the clinical outcome compared with the biomarker to show, before I will come out and say now we have a validated biomarker that can use either to predict outcome of the guidance for giving the optimal dose, because it's basic not in status to date. So that is one question, you have some more. I forgot some of them now.
Tiago Fauth -- Credit Suisse -- Analyst
Any interim data?
Jan Moller Mikkelsen -- President and Chief Executive Officer
The interim data is a good question in this way. We will be in [Phonetic] position where we see some active doses, we will be in a position that we have the opportunity to look at that, I thought we will have that part of the dose escalation.
Operator
Thank you. Our next question comes from Alethia Young with Cantor Fitzgerald . You may proceed with your question.
Alethia Young -- Cantor Fitzgerald -- Analyst
Hey guys. Thanks for taking my question. A couple; one, can you talk about your [Indecipherable] technology versus some others in the past. I get this question a lot from clients. And what do you think are the key considerations for regulatory approval? Also as it relates to the adult growth hormone trial, and not [Indecipherable] to discuss, but can you talk maybe a little about size and endpoint design of that study? And I just wanted to clarify on PTH the fast forward study, we'll get all 40 patients [Phonetic] of data at the end of the year and will we also get kind of any longer duration that exist beyond kind of what it does, what characterize on ClinicalTrials.gov thing?
Jan Moller Mikkelsen -- President and Chief Executive Officer
Let me start from the last question. We are still aiming up being in a position to provide the top-line data in the end of the year. We are still in a position that we will move the patient over in an extension study, sort of the long-term data. So for example, you can [Indecipherable] at six months to the data then there will be the six months data. So I expected in the middle of next year, we will have six months data from the extension study, and then we will continue, where we will have on predetermined intervals. We will have readout of at least 40-patient [Indecipherable] in the study.
Related to our TransCon Technology, yes, you are right. Ascendis Pharma is built on TransCon technology. We have basic the one and only company that have what are called technology platform that provide what we call the TransCon technology, which are basic and predictable sustained release of a product. No one basic have that. You see other company trying to mimic that part. You can see, for example, Nexa have tried to do it in the PEGylated IL2 with our basic and they are complicated way to make a product of IL2. And so other technologies platform is not really existing in the same level as you've seen with our TransCon technology. And this is why we have really a unique position is and the technology platform is very different compared to other technology platform that has been used.
If you go through the protein area, we have protein fusion that have been used and we already have seen that issued by protein fusion both related to change of mode of action. But also immunogenic potential on the permanent PEGylated product. We also have seen the complete different technology platform, where you have an entity that is basic and consisting of the target of the linker and the carrier and is also have the element of restricting this distribution volume. So when we talk about the technology platform and how we differentiate to come clear to our technology platform, everything from encapsulation technology, permanent PEGylation, protein fusion, no one really can be compared to the TransCon technology.
Jonathan A. Leff -- Senior Vice President, Chief Medical Officer
And, she asked about the adult program?
Jan Moller Mikkelsen -- President and Chief Executive Officer
The adult program. So we're finalizing the details of the adult program, but we've not yet completely harmonized across all the different regions and regulatory bodies. So it's a little premature to talk about the specific details and study design of the adult program.
Operator
Thank you. Our next question comes from Liana Moussatos with Wedbush Securities. You may proceed with your question.
Liana Moussatos -- Wedbush Securities -- Analyst
Thank you for taking my questions. Do you plan to partner the entire pipeline including oncology with VisEn in China. And can you remind us the terms for pediatric growth hormone?
Jan Moller Mikkelsen -- President and Chief Executive Officer
What we did within China was that we made a collaboration where we provided the three endocrinology products, TransCon Growth Hormone, TransCon PTH, TransCon CNP. So VISEN pharmaceuticals basic limit to what we call endocrinology. We have not done any kind of partnership at all with our -- for example, oncology pipeline or they are not anyway a limit and any kind of geographic regions.
The partnership with VISEN Pharmaceuticals is that we have a 50% ownership in the entity and as I said and the pre mark [Phonetic] was that it gives us a unique opportunity not only for being a position that we get our three product opportunities develop and commercialized in China, but we also, as Ascendis Pharma have an opportunity to conduct clinical trials for our product. For example, in achondroplasia in China through VISEN Pharmaceuticals. So we really believe that having this kind of productive approaches take us in, they are really unique. And the same time, we also have what we could call a potential upside that VISEN pharmaceutical could go public as an independent company either in Mainland or in Hong Kong sometime in the future.
Operator
Thank you. Our next question comes from Adam Walsh with Stifel. You may proceed with your question.
Adam Walsh -- Stifel -- Analyst
All right. Thanks for taking my questions. A couple here, just on TransCon Growth Hormone, you mentioned Jan that you've been proactive in identifying any potential review issues upfront and writing them into the BLA. That's terrific and I think you gave an example earlier, but I wonder if you could elaborate on that in terms of what are the potential review issues, if any, that you see and how are you approaching that in terms of the BLA filing?
And then just one other with respect to label expansions for TransCon Growth Hormone into additional pediatric indications like Turner SGA. Can you just clarify for us the approach that you will be taking there whether you intend to pursue formal label expansion studies or how you go about accessing those patient populations? Thanks.
Jan Moller Mikkelsen -- President and Chief Executive Officer
Yeah. Adam, thanks for the question. And I actually think that you're going up and saying is that first of all, my old conclusion is that I really cannot think of about an issue with I actually think that I should be concerned about. But what we really have done in our basic slide deck is that we have tried to say what is our key learnings and I have to think that is the main important part we have done in our evaluation is -- so I have to think that we are in a position is that we have really saw to. We have not seen anything that really give us some concern. We wanted to prove that we had the same balance to the team, the direct and indirect effect, because we know that by having that we really some way can be in a position that we can some way build on all the last 15 to 20 years, what I call safety, efficacy on it. I think, Jonathan and his people have really gone to all the major, you can say, safety part of the entire trials we had made not only our Phase III trial, but also our Phase II trial and I have to think, Jonathan, if you can come up with your conclusion.
Jonathan A. Leff -- Senior Vice President, Chief Medical Officer
Sure. So I mean growth hormone is a class, has some safety issues that have been well described over the years like slipped capital femoral epiphysis, benign intracranial hypertension, arthralgia slowing [Phonetic]. So we look at all of those, we've not seen those in our programs, but those are the sorts of the proactive issues that we'll describe very carefully to show that we've not seen them. And those are the kinds of issues that the agency, shortly we'll be looking for.
Jan Moller Mikkelsen -- President and Chief Executive Officer
With related to your second question, Adam, we have really working a lot with all of our commercial strategies and Tom and his team have got the mass order. How can they build a leading brand in less than three years? And one of the common feedback is what is the balance with team Phase III trials and Phase IV trails? How are we balance the different indications and I like to think what you see first is where we have a proactive Phase III trial happening and that is the first label expansion we will do, they will be in adult with growth hormone deficiency.
So I have to think, when you look on all the other indication where the growth hormone be used. You will see a mix of the team, Phase IV trial and Phase III trials. And this is how we basic will build and expand the growth hormone market in the future. Growth hormone adult is interesting, because it's under penetrated, have just only penetrated down to 15% to 20% and we believe potential [Phonetic] if we conduct a really successful Phase III trial in adult growth hormone deficiency, we can drive an expansion of this market and there is other indication where we potentially can see there is a huge benefit to make a Phase III trial potential with the -- we can phase, facilitate an expansion of this specific market segment.
Operator
Thank you. And our last question comes from Joseph Schwartz with SVB Leerink. You may proceed with your question.
Juri -- SVB Leerink -- Analyst
Hi. I am Juri [Phonetic] dialing in for Joe. Thank you for taking our questions. I am wondering if you can expand on the percent of patients with IGF-1 standard deviation greater than two and three for the Phase III fliGHt Trial data that you provided at your R&D Day. Could you provide the number or the percentage of patients with consecutive observations greater than two and three standard deviations in your fliGHt Trial?
Jan Moller Mikkelsen -- President and Chief Executive Officer
Because the question you asked is, need to be little bit more reflecting back of the Data we are providing. For example, if you go back to our current slide deck and go to the new data we are providing how we serve, you can basic [Indecipherable] up and down and it gives you a little bit of perspective, about the IGF-1 levels to see in the patient group with our fliGHt Trial.
So if you go to Slide number 29 and then you can see that when we -- we look then this patient, the 29 patients that went through a down titration and this 29 patient went to an -- had this [Phonetic] dose reduction of 0.0445 [Phonetic] milligram per kilo per week. And then before we would like to see what is we did -- the demographic of this patient group and when we look at them they were on a daily growth hormone dose of 0.28 milligram per kilo per week. This is basic the same group that the average of the entire fliGHt was 0.29. Perhaps a little bit, 0.01 just.
But when you look on the baseline IGF-1 is that is you can basic see that the ability and what kind of execution because you can basic from a mathematic model then calculate out from the [Indecipherable]. The baseline IGF-1 is based on daily growth hormone, was 2.0, meaning is that you're going to see the frequency of that, that is higher on three, that is higher on four. This is patient that is on daily growth hormone. So you can always say that, this reflect typical what you see in the US population, where you all see more than 30%, 40% of all measuring being done on IGF-1 higher than two.
What we also saw they saw because we take them on an 0.24 milligram per kilo per week dose that basic are in a position that they get higher IGF-1 because they are much more effective compound we have, with about 40% to 50% more effective. And what we can see, you just lower the dose with the 20% and then you basic are done 0.246. And if you were in a position that your basic will lower again with 20%, then there will be basically down to the starting dose. So this is how you function in the clinical system today. How you really are as a physician with other product. You look holistic on the patient, do you really look at the age, the gender, looking on what is the time before the gold plate [Phonetic] close as only have the treatment opportunity to one to two years. I want to give the optimal benefit to the patient and do the treatment according to that.
Operator
[Operator Closing Remarks]
Duration: 63 minutes
Call participants:
Scott T. Smith -- Senior Vice President, Chief Financial Officer
Jan Moller Mikkelsen -- President and Chief Executive Officer
Jonathan A. Leff -- Senior Vice President, Chief Medical Officer
Josh Schimmer -- Evercore -- Analyst
Tazeen Ahmad -- Bank of America Merrill Lynch -- Analyst
Jessica Fye -- JPMorgan -- Analyst
Michelle Gilson -- Canaccord Genuity -- Analyst
Jim Birchenough -- Wells Fargo Securities -- Analyst
Tiago Fauth -- Credit Suisse -- Analyst
Alethia Young -- Cantor Fitzgerald -- Analyst
Liana Moussatos -- Wedbush Securities -- Analyst
Adam Walsh -- Stifel -- Analyst
Juri -- SVB Leerink -- Analyst
