Ascendis Pharma A/S (NASDAQ:ASND) Q2 2020 Earnings Conference Call August 27, 2020 4:30 PM ET
Scott Smith – CFO & SVP
Jan Mikkelsen – President & CEO
Dana Pizzuti – SVP, Development Operations
Conference Call Participants
Michelle Gilson – Canaccord Genuity
Joori Park – SVB Leerink
Joshua Schimmer – Evercore ISI
Jessica Fye – JPMorgan Chase & Co.
James Birchenough – Wells Fargo Securities
Tazeen Ahmad – Bank of America Merrill Lynch
Alethia Young – Cantor Fitzgerald & Co.
Trevor Allred – Oppenheimer
Ladies and gentlemen, thank you for standing by, and welcome to the Second Quarter 2020 Ascendis Pharma Earnings Conference Call. [Operator Instructions].
I would now like to hand the conference over to your speaker today, Scott Smith, Senior Vice President and Chief Financial Officer, at Ascendis Pharma. Please go ahead.
Thank you, Operator. Thank you, everyone, for joining our Second Quarter 2020 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; Dr. Dana Pizzuti, Head of Development Operations; and Dr. 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, but 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 most recent annual report on Form 20-F.
Please note that our TransCon prod candidates are investigational product candidates and not approved for commercial use. As investigational products, the safety and effectiveness of the TransCon product candidates have not been reviewed or approved by any regulatory agency. 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 2020 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 Mikkelsen, our President and Chief Executive Officer. Jan?
Thanks, Scott, and good afternoon, everyone. This second quarter, we achieved several key milestones for Ascendis. As we continue to advance towards our Vision 3×3 to build a fully integrated biopharma company. We submitted our first BLA to the FDA for TransCon Growth Hormone for the treatment of pediatric growth hormone deficiency in June. The BLA submission was completely in line with our stated 2020 corporate goals. And it moves Ascendis, another step closer to become a fully integrated global biopharma company.
To see our first TransCon technology product, TransCon Growth Hormone, progressed from the idea stage through 3 Phase III clinical programs, covering over 400 subjects and into a regulatory filing, which also includes our auto-injector, makes me proud of what we have achieved. But we are not stopping here. What makes Ascendis unique is that we are a global company with a broad, diversified pipeline where all product candidates are created with the TransCon technology platform.
With the TransCon technology, we are able to leverage the validated biology of assisting drug and create highly differentiated product candidates by identifying significant unmet medical needs with well-defined clinical strategies, starting with signs underlying the disease. And applying our TransCon technology to an existing clinically validated parent drug or pathway, we are able to create a new product candidate, solving the unmet medical need. Starting with known biology, we are able, quite simple, to create highly differentiated products with large commercial potential with an expected high success rate. To achieve our goal of sustainable long-term growth, we will continue our algorithm of building multiple high-value product opportunities in endocrinology rare disease, oncology and a third therapeutic area. The BLA filing for TransCon Growth Hormone in the U.S. is just one more milestone for Ascendis towards achieving our Vision 3×3 strategy to be a leading biopharma company.
We also continue to execute across other areas of the company. Let me update you on some of this recent development. For TransCon Growth Hormone. After the BLA filing, for the treatment of pediatric growth hormone deficiency, Ascendis received a positive opinion from the Pediatric Committee of the European Medicine Agency, PEDCO. On this agreement with the proposed Paediatric Investigation Plan or PIP, covering children from six months to less than 18 years of age. We are pleased by the PEDCO decision because we believe it reflects the unique product features of TransCon Growth Hormone, which enables the long action release of unmodified somatropin. By releasing unmodified growth hormone, the same molecule as daily growth hormone, all in daily growth hormone.
The TransCon technology is designed to levels both the direct and indirect effect of growth hormone in the same balanced way as daily growth hormone has for decades. To our knowledge, the approval of our PIP is the first time PEDCO has concluded that a development program for a long-acting growth hormone treatment support the clinical development in children. With the approval of the PIP, we are on track for filing the M&A or marketing or taxation application in Europe this quarter, instead of the planned Q4 2020 filing. To establish global clinical reach for TransCon Growth Hormone, we continue to advance on several fronts. In Greater China, VISEN Pharmaceuticals, our strategic investment, continues to enroll subjects in a Phase III trial for TransCon Growth Hormone in pediatric growth hormone deficiency. In Japan, we remain on track to initiate the Phase III trial for TransCon Growth Hormone in pediatric growth hormone deficiency in the fourth quarter. For indication label expansion, we continue to execute on our global Phase III trial evaluating TransCon Growth Hormone in adults with growth hormone deficiency. Why is this trial so exciting? Daily growth hormone treatment for children and adults with growth hormone deficiency, support overall endocrine health, including improved body competition, mental health, cardiovascular health and bone health, in contrast to pediatric growth hormone deficiency, where we measure height as primary endpoint. In adult growth hormone deficiency, we typically measure the impact on altered body composition, such as change in truncal fat mass or lean body mass. To achieve this optimized clinical effect on truncal fat mass, it’s essential that growth hormone has its direct effect on the target tissue, as the decrease in truncal fat mass by growth hormone is partly facilitated by the direct activation of the growth hormone receptor on truncal fat cells.
Our adult growth hormone deficiency trial, the foresiGHt Trial is a global Phase III trial designed to compare the safety and efficacy of once-weekly TransCon Growth Hormone with placebo and a daily growth hormone product. The foresiGHt Trial will be conducted in around 120 sites, in North America, Europe, Asia, including China and Japan. Around 240 adult subjects with growth hormone deficiency who are treatment-naive or have not received growth hormone therapy for at least 12 months prior to screening will be enrolled in the trial.
Subjects will be randomized 1:1:1 across 3 arms with expected 80 subjects in each arm. Once-weekly TransCon Growth Hormone, placebo administrated once per week and a daily growth hormone product. The once-weekly TransCon Growth Hormone and placebo arms will be double-blinded and the daily growth hormone arm will be open label. The treatment period will be 38 weeks with 12 weeks for dose titration and 26 weeks for maintain. The primary endpoint is the change from baseline and truncal fat percentage at week 38. Secondary efficacy endpoint, a change from baseline in truncal fat mass and change from baseline in total lean body mass. All expiratory endpoints will be assessed along with the patient-reported outcome measures, safety, PK and PD.
The primary regulatory objective is to evaluate the efficacy of once-weekly TransCon Growth Hormone versus placebo. From a commercial perspective, it is important to show at least comparable efficacy, safety and tolerability to daily growth hormone. Adult growth hormone deficiency is the least penetrated market segment for growth hormone, with well-documented adherent challenges and health challenges. We believe TransCon Growth Hormone may provide an alternative to daily growth hormone that address overall endocrine health. And may provide a convenient alternative, which also leads to a better outcome for adult patients and expansion of the growth hormone market.
Moving to TransCon PTH. The data we have reported from the 4-week fixed-dose, double-blinded period of PaTH Forward in April 2020. Combined with the additional data we reported this afternoon demonstrated, for the first time, we believe that potential to transform the lives of people living with hypoparathyroidism with a hormone replacement therapy. Earlier this year, in April, we reported top line data from the 4-weeks fixed-dose, double-blinded portion of our Phase II PaTH Forward trial, which demonstrated that TransCon PTH has the potential to replace the standard of care, activated vitamin D and calcium supplements. The data reported to date support our view that TransCon PTH could replace standard of care. In just 4 weeks, 80% of [indiscernible] on TransCon PTH removed standard of care compared to 50% on placebo, even if subjects were kept to a fixed dose of TransCon PTH. In our open-label extension trial, subjects are allowed to optimize up and down the TransCon PTH dose. So we expect that additional subjects might be able to remove standard of care.
We have been pleased to see all 58 subjects in the open-label extension trial are continuing in the trial at the 6-months point. These subjects have been kept continued regardless of baseline pill burden, severity of disease and whether they had a response or not in the 4-week portion. We believe for this excellent retention that there may be some positive effect of PTH itself, independent of historic pill burden and other biochemical parameters that we have reported out. What we have not known is where PTH therapy may improve quality of life for the patients. Today, we released new data, which we believe is another element in demonstrating that TransCon PTH is better than standard health care for treating HP patients, and support TransCon PTH as a hormone replacement therapy.
It is the first time, to our knowledge, that a treatment for hypoparathyroidism has demonstrated a statistically significant improvement in quality of life compared to placebo in a double-blinded controlled trial using the SF-36 Health Survey, a commonly used and validated nondisease-specific PRO instrument for overall assessment of health and well-being. The survey consists of 36 questions, and the results are summarized in a physical component summary, PCS, and mental component summary, MCS.
At baseline, in the Phase II PaTH Forward trial, subjects in both arms of the trial had a lower than average SF-36 scores, suggesting that there is a reduced health-related alive in this patient population. This is in alignment with several other targets. Already in the 4-weeks double-blinded controlled part of a Phase II trial, specific significant and clinically meaningful improvement in PCS and MCS were observed. For the PCS score using a normative scoring system with a score of 50 as the norm for general population and an ANCOVA model, TransCon PTH subject demonstrated a mean difference of 5.2 points compared to placebo with a p-value of 0.013. The minimal important difference for PCS is 2 points. Fundamental component summary score, TransCon PTH subjects demonstrated a difference in mean of 9.8 points compared to placebo with a p-value of 0.0003. The minimal important difference for MCS is 3 points.
Our four week data suggests that sustained normal PTH levels offers something else rather than just normalization of serum calcium. Both PTH-treated and placebo subjects seek high rates of normal calcium, 92% and 80%, respectively. Yet, there was a meaningful difference in quality of life scores. Based on clinical experience, clinicians and patients with hypothyroidism have not discussed that physiological PTH levels contribute to optimal function of the central nervous system. Our 4-week data suggests that sustained normal PTH level rather than just normal serum calcium is indeed associated with health benefits. While these data are considered exploratory, there are the first dividend we ever seen for a randomized double-blinded controlled trial indicated that a treatment for HP compared to placebo may have a significantly improved physical function as well-being towards a normal level.
In previously published randomized control trials of PTH product where SF-36 was compared to placebo, no significant treatment difference was detected versus placebo. One possible explanation for this finding is the lack of sustained PTH levels. We continue working on validating our own disease-specific PRO instrument to help us evaluate additional patient benefit of TransCon PTH that may strengthen our overall value proposition. We plan to discuss our 4-week double-blind data and 6-month open-label extension data for our own disease-specific PRO instrument and SF-36 with FDA in the coming months.
We remain on track to report 6-months data from the open-label extension portion of the PaTH Forward trial this quarter and some regulatory filings to initiate a global Phase III trial of TransCon PTH in North America and Europe in the fourth quarter. We have initiated our global end of Phase II meetings with regulatory authorities and are pleased with the feedback so far.
From the results that we are seeing in our Phase II PaTH Forward trial, we believe that TransCon PTH potentially represent a new treatment paradigm for HP as replacement therapy, a therapy that might be able to replace conventional care, normalize biochemical parameters and associated long-term risk factors and improve the quality of life for patients. We look forward to sharing the 6-months open-label extension data with you later this quarter. A quick update on the rest of the pipeline. For TransCon CMP, we continue to work towards escalating dose cohorts in the ongoing ACcomplisH Trial. Our global Phase II trial that is evaluating the safety and efficacy of TransCon CMP at escalating doses in children with achondroplasia from 2 to 10 years of age. We received Orphan Designation from the European Commission for TransCon CMP for achondroplasia, giving us Orphan Designation in both Europe and the U.S. As part of an integrated global clinical program, clinical development in China is being done to VISEN Pharmaceuticals. There, an independent Phase II ACcomplisH China trial is expected to be initiated in the fourth quarter.
Moving to oncology. Quick clinical data for TransCon IL-2 beta/gamma, a product candidate designed to provide sustained systemic relief of the receptor bias IL-2, IL-2 beta/gamma specific, were presented at the American Association of Cancer Research Meeting in June. These data show the potential of TransCon IL-2 beta/gamma to be best-in-class IL-2 molecule, and demonstrated that a single dose in nonhuman primates provided a potent expansion and activation of cytotoxic lymphocyte with low activation of Treg cells and eosinophils. In addition, a long half-life of around 32 hours were observed in nonhuman primates, which is expected to support potential dosing of every three weeks in patients. We are on track to submit the first IND filing or similar for TransCon TLR 7/8 Agonist in the fourth quarter 2020, followed by a planned IND filing or similar for TransCon IL-2 beta/gamma in 2021. Based on the promising preclinical results we have seen in our TransCon IL-2 beta/gamma and TransCon TLR 7/8 Agonist product candidates, we believe our TransCon technologies, which enable both systemic and long-acting inter-tumor admiration have the potential to improve treatment outcome for patients with cancer.
As you can see, our clinical pipeline progress has kept Ascendis very busy during the first half of 2020. During the current quarter, we continued to grow our headcount in both R&D and the commercial organization as we’re preparing for a potential launch of our first project and expand our pipeline and global key initiatives.
Now let me turn the call over to Scott for a financial review before we open for questions.
Thank you, Jan. Turning to our financial results for the quarter ended June 30, 2020. We reported a net loss of €94.9 million or €1.97 per basic and diluted share compared to a net loss of €58.9 million or €1.25 per basic and diluted share during the same period in 2019. Now I will run through some of the key components of these results. Research and development costs for the second quarter were €63.6 million compared to €43.8 million during the same period in 2019. The increase in R&D costs reflect continued advancement of our pipeline with the primary drivers, including for TransCon Growth Hormone, costs were higher compared to the same period of the prior year due to increased costs related to manufacturing of commercial product supply as well as increased clinical trial activities, including start-up costs for the global Phase III adult GHD trial, the foresiGHt Trial. And the Phase III pediatric GHD trial in Japan.
And for both TransCon PTH and TransCon CMP, costs were higher primarily due to increased clinical trial and manufacturing costs. We also saw higher external costs related to the continued build-out of our oncology therapeutic area and across all programs, an overall increase in personnel-related costs. Selling, general and administrative expenses for the second quarter were €20.8 million compared to €11 million during the same period in 2019. These higher costs primarily reflect an increase in personnel and related costs, as well as expenses associated with the continued build-out of our commercial capabilities.
Other income and expenses included an unrealized noncash loss of €9.9 million compared to an unrealized noncash loss of €8.2 million during the same period in 2019 due to foreign currency exchange rate fluctuations. We ended the second quarter with cash, cash equivalents and marketable securities totaling €471.6 million.
In July, subsequent to quarter end, we completed a follow-on financing with net proceeds of USD 654.7 million or approximately €580.7 million. Including net proceeds from the July offering, pro forma cash, cash equivalents and marketable securities, as of quarter end, would have been approximately €1 billion. We also remain on track to achieve the following milestones for the remainder of 2020: for TransCon Growth Hormone, these include submitting the MAA filing in Europe during the current quarter; executing the foresiGHT trial, a global Phase III study for adult GHD; and initiating a Phase III clinical trial for pediatric GHD in Japan in the fourth quarter. For TransCon PTH, these include reporting 6-month open-label extension data in the Phase II PaTH Forward trial in the third quarter and initiating the global Phase III clinical program for adult hypoparathyroidism in the fourth quarter.
For TransCon CMP, this includes initiation of ACcomplisH China, a Phase II clinical trial for achondroplasia through our strategic investment in VISEN Pharmaceuticals in the fourth quarter. And lastly, in our oncology therapeutic area, we continue to invest in CMC and preclinical activities related to TransCon TLR 7/8 Agonist and TransCon IL-2 beta/gamma, and we plan to submit our first IND or similar filing in the fourth quarter for our TransCon TLR 7/8 Agonist.
We continue to execute on our goal of building a leading biopharma company with a diverse pipeline of potential high-value product candidates in multiple therapeutic areas. Combining our TransCon technology with clinically validated parent drugs in areas of well-known biology has allowed us to deliver unique product candidates and clinical results with an expected high probability of success. We saw that first with TransCon Growth Hormone where, for the first time, we are aware of a long-acting growth hormone demonstrated in a randomized controlled clinical trial, similar or superior efficacy and safety on a broad spectrum of parameters compared to a daily growth hormone. Today, you see similar results from the 4-week randomized double-blinded fixed-dose portion of PaTH Forward with TransCon PTH, which demonstrated, for the first time to our knowledge, that a treatment for hypoparathyroidism had a statistically significant improvement compared to placebo for the SF-36, a commonly used and validated nondisease-specific PRO instrument for overall assessment of health and well-being.
We look forward to potentially sharing similar firsts with you in our TransCon CNP, TransCon TLR 7/8 Agonist and TransCon IL-2 beta/gamma programs in the coming years. With our recent follow-on financing, we remain well capitalized to execute on our Vision 3X3.
Operator, we are now ready to take questions.
[Operator Instructions]. Our first question comes from the line of Michelle Gilson with Canaccord Genuity.
Congratulations on the data. I know it’s not apples-to-apples because of the duration of treatment and the baseline. But perhaps you can expand a little bit on some of your comments about this being the first trial to show a difference in quality of life for SF-36 results in a randomized placebo-controlled study. And maybe specifically, you can help us understand if there’s a comparison to be made with the results from the REPLACE study, which showed that net par treatment did not result in a statistically significant improvement in either of those domains compared to placebo?
Thanks, Michelle. Why we really are so excited about the data is because we basically had been missing something because — and when we started our TransCon PTH product, we had a long discussion about how do we really describe the severity of the disease. And people try some way to describe it from the pill burden. And when we look on the patient demographic that we have enrolled in our Phase II trial, some of the patients is definitely being placed in the group of mild, taking low amount of activated vitamin D, taking a low amount of calcium supplement.
And then we have the more moderate and then we have the severe, but what we saw — because all the 58 patients now is past this 6-months step. And then we know the burden of daily administration, but still patients are staying and not dropping out.
And typically, I have seen many trials, tried many trials. Typically, I would expect in the open-label extension, we will already — have seen a lot of drops out. Why are all the — and then including the mild patient there must be something else which we cannot just get from biochemical analysis. And this is why we develop the disease-specific PRO patient-reported outcome for hypoparathyroidism because we wanted really to cash that and get it validated and seen. The SF-36 is what we call it nondisease-specific validation, just describing the benefit you can really achieve in the well-being of a person and what we saw here is that SF-36 came out so clear in just the first four weeks.
And we believe that is because we are providing the physiological PTH level 24 hours, seven days a week, meaning it’s a flat curve without huge flotations. And this is why we believe other product has not been possible to show a significant change in SF-36 when they have a double-blinded period. And I actually believe this is just talking about the strengths of the product opportunity. But I think perhaps more important, for me and Ascendis, is we really see the benefit that the patient get. We see how they really are changing their life. They are coming and adapting more to a normal life because they get the right hormone replacement therapy.
Great. And just as a follow-up, are you planning to report the PRO with your 6-month data later this quarter? And just moving forward, when we do get those data without a placebo arm in the open-label extension study, how should we think about interpreting the PRO or SF-36 results?
I think we both have the SF-36 results. But then, Dana, you can comment about our…
Right. Yes, as far as our own PRO instrument, the HPES, we’ve already submitted to the FDA, the documentation to get that validated by them. And so it’s really not so much to look at the individual groups and how patients fit, but more about the instrument itself, how it behaves, how predictive it is. And as we have talked about before, there were the two major aspects of that, which was the symptom side of it and then the impact side.
So we’re pretty excited that it seems to function quite well. But the thing is that it’s not validated. And the reason that we came forward with SF-36 was because it’s a validated instrument, again, not specific for hypoparathyroidism, but well-established in terms of patient well-being, as Jan mentioned.
And so we’ll be able to sort of correlate actually both of those scales as we go forward. Now the issue that we’re going to have in interpreting the 6-month data is that there’s no control arm beyond the first four weeks. So we can follow and see how patients do. And based upon what we’ve seen so far with patients, as Jan said, staying on the trial, we would expect nothing less than a maintenance or an improvement in the four week results we got from either the SF-36 or the HPES data as well. So again, we will be looking at that very closely once we finalize the 6-month data in all of the 58 subjects that are still in the trial.
We have never had any doubt there was a reduced health-related quality of life in patients with hypoparathyroidism. There is multiple application that’s showing that. But what is the interesting part for me from a high-level scientific perspective is that it looks like this level can be independent on calcium levels. And this is where I think that what we’re seeing more and more, is potential and direct CNS effect that is providing this benefit related to health-related quality of life.
And this is what we will like to sustain further with both our own PRO but also continue measuring SF-36. But we are really interested about these results because it’s really are the best thing you ever can see when you see the huge benefit that you can provide with an endocrine product where you’re basically also providing a high level of health-related quality of life.
Our next question comes from the line of Joseph Schwartz with SVB Leerink.
Hi. I’m Joori dialing for Joe. So the first one has to do with the [indiscernible]. We were just wondering if you talked to the FDA about the SF-36 data, and do you have a sense about how the FDA feels about the study design and primary endpoint for Phase III?
I think we just got that data now. This is why we released it here together with our Q2 earnings. And definitely, Dana and her team will really go in and discuss it with FDA. You can comment on that, Dana.
Yes. I mean we actually are preparing to communicate not only these data with just about the SF-36, but also the 6-month data once we get that all compiled and finalized. So in addition to validating our new instrument, the HPES, we’ll talk further about the SF-36 and the long-term efficacy and safety of the product after the 6-month time period.
So in conclusion, we have not shown regulatory agencies this data yet. We are going to do it together with our 6-month data that’s coming later this quarter.
Okay. Great. That’s helpful. And then if I could just dive a little bit deeper about your HPES PRO, could you just talk a little bit more about it? What potential differences could there be between your HPES PRO and SF? And what do you believe, obviously, you just resubmitted it and it’s in the hands of the regulator, but what do you believe — or what do you wish to capture with your PRO that the off-the-shelf endpoint of SF-36 would not be able to?
Well, I think that the major difference is that this has been developed and sort of validated in hypoparathyroidism patients, right? And so SF-36 has been around for quite a while. It’s been used in all sorts of therapeutic areas for sort of looking at how the patients react or respond to therapies. So what we were able to do, though, as we look at the different — for instance, the symptoms, many of them that are sort of more prominent or more of a problem in patients who have hypoparathyroidism. So CNS things around remembering and concentration, which are the big things that patients tell us about this brain fog and things like that. So we ask specific questions about that. And then as well, other, like less CNS-related symptoms are also part of the different queries that we make to the patients.
And so that’s the symptoms side. And then on the impact side, then it becomes a question about, so how much better or worse are you with respect to your sort of general physical activity, okay? Your ability to work, your sort of mood. And then also your social relationships. So those are like the different parameters like on the impact side. But again, the big difference is that it’s validated in patients with hypoparathyroidism.
Our next question comes from the line of Josh Schimmer with Evercore ISI.
I have three of them. First, on the foresiGHT trial, can you describe the dose and titration schedules for the weekly and daily treatment arms? For the CN — actually, still on the growth hormone market, you had indicated that the adult growth hormone market is under-penetrated. Maybe you could talk a little bit more about the unmet need, the symptomatology and the benefits that they could derive from a convenient growth hormone option? And then when do you think we’re going to get a clear sense on the TransCon CMP candidate profile in terms of its differentiated effect on growth specifically in patients?
Let me start with your last question. Yes. It’s a good question. When we are getting the efficacy on the right cohort, we are dose escalating now and what we already know from our knowledge about the product profile. We basically already think it’s highly differentiated because it’s continuous exposure of CMP molecule without the high peak that is associated with any effect on vasodilation and other things like that. And we see the efficacy is really highly differentiated, too.
When we will see the impact on this highly differentiated product opportunity in the clinical trial, we will see when we are going to state in our dose escalation cohort that we’re finding the right dose that is providing. And what we call high meaningful efficacy, not only related to high, but also related to potential other comorbidities. I will hope and expect but I don’t know. I hope we will see that in a time where the next 6 to 9 months, but I cannot guarantee that because I do not know which one is basically the right cohort where we will see the effect that we want to have. Related to adult growth hormone deficiency is a quite different patient population that you basically see in growth hormone deficiency in pediatric where many of the adult patients are coming from a complete different background, meaning there’s only 15% to 20% that basically are coming from the pediatric growth hormone deficiency.
Many of them are coming from the cancer setting oncology, coming from trauma and other places where they have and decreased amount in growth hormone. This here is basically underserved. There has been a lot of different serves about what is the penetration. People are talking about 15% to 20% is really getting treated of the total patient population. So it definitely is a possibility to both help a lot of patients in adult growth hormone deficiency because it’s very hard for them to adhere to the daily injection, and we can move them over to a once-weekly dosing.
Typically, and what we wanted to do in our foresiGHT trial, which is built in such a way we have a 1:1:1 randomization because we think it’s not only important to show that we are better than placebo from a regulatory perspective, but the real product out there is daily growth hormone. So we want to be sure that we at least get the same efficacy as daily growth hormone. And in the site, how we titrate them up, you try to titrate them up in the same manner that you will see with daily growth hormone where we start on a low dose because the issue is how to get the body to adapt suddenly to have growth hormone again. And when the body is getting used to that, you basically can titrate up to what I call normal IGF-1 level.
Our next question comes from the line of Jessica Fye with JPMorgan.
In PTH data today, I’m curious if the 4-week SF-36 results or the HPES results track with the biomarker and supplement withdrawal components of the primary and key secondary efficacy endpoints in PaTH Forward. Essentially, were the responders on the primary and secondary more likely to benefit on SF-36 or HPES than the nonresponders? And related to that, it sounds like you’re saying that some patients benefited meaningfully on quality of life, even if they did not meet the responder criteria for some reason. And if so, I was hoping that we could dig into which element of the responder criteria seemed less important for quality of life. You alluded to calcium in response to an earlier question. Was that serum calcium or urinary calcium?
I think we have still a lot to learn about how really TransCon PTH have so many positive effects when you have a normal replacement therapy. What we could not see any clear correlation was reflecting a serum calcium. And any kind of the parameter related to quality of life. So that was one of the more interesting perspectives we wanted to analyze.
Taking to the next deep dive, we have not reached yet, and we will continue to analyze other any kind of the subgroup of the SF-36 where you can subgroup it further down in the 36 questions in different domains, where some of them are much more reflecting to one single parameter of the other one. We are not to the level where — at least I’m not seeing analysis that basically are describing any kind of correlation or lack of correlation. But it’s basically a very, very interesting topic what we really will follow up on. What we basically are coming from is that what we see in our SF-36 is also some of the same positive trends that we’re seeing in our disease-specific PRO. So I think there is a great alignment in the data.
Okay. And following up on that. Do you see any possibility of changing the planned Phase III endpoint to SF-36 or HPES?
I actually believe that when we look in our primary endpoint, we actually will include such a parameter potential as a key secondary element, which are a great way to also have an opportunity to isolate and be ensuring that we can either build it on our patient-specific PRO, but we can also include element as SF-36. So definitely, we have a chance, but we are not thinking on building it into the primary endpoint, but basically take it up as a key secondary endpoint.
Okay. Great. And last one, maybe a quick one. Is it possible to refine when, in the third quarter, we can expect the 6-month PaTH Forward update?
It’s not so many months left now in the third quarter now. So I actually think that they will be — there’s only one month left now, basically September. So it will be in the next 4 to 6 weeks.
Our next question comes from the line of James Birchenough with Wells Fargo.
Congrats on another strong update. A couple of questions. I guess first, maybe not to pick on data, but just on the mental component of the SF-36, it just seems like there’s a pretty substantial decline in the placebo group from baseline to week four. Is that an expected natural history? And is the drug result specifically superior to the baseline of the placebo? I’m just trying to understand if the decline in the placebo contributed to the results.
I have not got any feedback, Jim, that indicates that the decline, anyway, should be reflecting any kind of the treatment outcome there. So I have not seen that part in this. But what you will see is that everyone has been normalized to the 50 account. And I think that is where we see the norm generation general population. So when you have a number, you basically transform it into a normalization.
Got it. Okay. Yes, it just looked like the baseline was at around 47 for placebo and then dropped down to maybe 42, and that was part of the delta with the treatment effect at week four. So I was just trying to understand that a bit better.
Exactly. But I think this is how you make the different domains and then make it over in a summary scheme where you normalize it to a norm scheme. And this is where you basically will see this kind of difference coming in.
Got it. Okay. And then just in terms of going beyond the 6-month data this quarter, the interactions with regulators. When should we hear back on the results of those interactions? And is breakthrough designation part of the discussion?
So currently, we are only discussing with regulatory agencies, our first 4 week data. There was the fixed-dose, double-blinded part. And in this discussion, we had not even included our SF-36 data. What we have discussed is how do we look about our 4 week data with basically are proving one single thing that we have with replacement therapy. The regulatory feedback where we have got regulatory feedback now from the U.S.. We’re getting, in beginning of September, regulatory feedback for different European agencies. And out from this feedback we got from U.S., that basically are understanding, yes, this is a replacement therapy. I believe there is an essential data target that will come up when we can come and discuss and send in our six month data in addition of the element we have from our SF-36 for the first four week double-blinded period. And also our disease-specific PRO, which we also will include as soon as we have got the 6-months data.
And maybe just one final question, just on the adult growth hormone deficiency. Could you maybe give us a sense of the burden of the abnormal body composition in adult patients with growth hormone deficiency? And what’s a clinically relevant change in that metric? And what is the consequence of that? And I’m imagining there are drastic metabolic consequences of those change parameters. But maybe just a bit of background, if you would, on just the body composition metric and what level of change would be meaningful?
Yes. You can say that in pediatric growth hormone deficiency, we measure height, but it is not the same thing to say in this patient population that body composition is also extremely important. But as a primary endpoint, your basic is always measuring high velocity for 1 year as an primary outcome. If you go to adults, of obvious reasons, they are not growing in height but typical in a different dimension. And this is where you are often measuring a decrease in truncal fat because growth hormone has a direct effect of breaking down truncal fat.
They also have major impact on other elements like a patient-reported outcome and also have impact on cardiovascular parameters, has impact on exercise capacity. But from a traditional perspective, how it always have elevated as a primary outcome, growth hormone treatment has been done in a pediatric population by high velocity, and in adult population on the decrease on truncal fat typical as a percent or absolute amount and increase. And secondary is something like increased lean body mass. This is not the same thing that you always would expect that overall positive effect you can get on endocrine health by growth hormone treatment is also expected to be associated with this decrease in truncal fat.
Our next question comes from the line of Taz Ahmad with Bank of America.
Okay. A few questions for me, for SF-36, in the three doses that you studied, the 15, the 18, the 21, can you give us an idea of how the response has changed as you went from the low dose to the higher dose? Just trying to get a little bit of granularity on that. Specifically, can you talk about whether the highest dose did show the best results? And then I have a couple of follow-ups.
I have not seen the breakdown directly on the 3 different patient group. It’s mainly being done on PTH arm and placebo arm and it was how the primary analysis was done. I am not sure there is any kind of difference between different groups, because that has not been brought up to my attention. So I actually think there will be a same positive effect on all the three different groups.
Okay. Going to GHD for a second. So you have Phase III now ongoing in China, and a Phase III starting in Japan soon. Can you give us a little bit more color on the time line for how you’re thinking about when those studies should readout? And then to follow-up on that, we traditionally have a sense of rare disease launches in Japan and price points. But can you talk to us a little bit, Jan, about how you’re thinking about the market in China?
Yes. TransCon Growth Hormone is being evaluated by our strategic investment, VISEN Pharmaceutical, in Greater China. They are in a situation where they are enrolling patients. They expect that in the end of first quarter next year, it will be fully enrolled. And therefore, you can basically expect that after 12 months, you will see — and some months to clean data, you will see the endpoint. If we go to the — Japanese trial is a smaller trial.
The Chinese trial is about 150 patients. In Japan, it will be much, much, much less. And we will start to enroll this patient group here in filing the IND equivalent in Japan end of this year. The growth hormone market in Greater China and Japan are interesting because it’s basically number two or number three single largest market. And the growth hormone market in China is as typically dominated a lot with local player where there is 1 company that’s providing, I think, the vast majority of the growth hormone.
And what is interesting is that we can come in, in this interesting market, which is very different compared to a traditional Chinese market because 75% of that is basically not in the hospital segment, but basically a direct payment from the caregivers. So it’s very, very different market compared to the general segment. And size of it is pretty large. Our best estimation is about USD 600 million to USD 700 million is the established Chinese market now and actually growing really large every year.
The Japan market is nearly in the same size and also have been pretty well-established for many years. So when we think about TransCon Growth Hormone, and really, we want to be the leading brand, we want to be the leading brand in a global manner. This is one of the reasons why we have hired a person like Jesper Høiland, which is coming from a global commercial background. And want to implement our rare disease endocrinology products on a global basis.
Some of the countries, we will go direct as the U.S. and selected European countries. Other places you will see, we use our innovative way of really building up strategic alliance where we at the same time can be part of really getting the value that we are creating, like we did with VISEN Pharmaceuticals in Greater China. And you will see this kind of way of thinking be implemented in a lot of other geographic regions where we accept that we need to have local knowledge, local people really to make it to a leading brand.
Our next question comes from the line of Alethia Young with Cantor Fitzgerald.
One, can you talk a little bit about why you kind of decided to focus first on TLR 7/8 versus maybe like IL-2? I just wonder if there’s anything you’re seeing preclinically or commercial that kind of makes you think about the landscape. The second question is talking a little bit about the CMP trial, has it been potentially impacted by COVID or is it just an element of dose escalation? And then my third question is, just have you gotten any feedback from the FDA on the growth hormone submission since you filed probably about late June?
Yes. Let’s start from the backlog of your question because then I can easily remember them. So you’re right, the 60 days period has passed and Dana, please inform.
Well, right. So the agency has confirmed that they filed it, but we’re still waiting for the day 74 letter. So that will disclose what the review period will be, whether they think we might go to advisory committee or any other issues they’ve identified, but they have confirmed that they have filed the application.
Second question related to TransCon CMP. I don’t think we have disclosed any kind of information about when we expect to have and what we call the cohort where we expect to see our own expectation to efficacy. We have not disclosed that, and we are still on track to follow the pattern that we have laid out. The only thing we have disclosed was we expect to initiate a trial, which is a double-blinded placebo-controlled trial in achondroplasia patient down to the age to 2. We have disclosed that we expect to initiate that end of this year, we call it ACcomplisH China, and we still expect to initiate this trial by end of this year.
My first question was on TLR 7 and 8.
That is a good question in it. And the 2 project was competing at the same time frame. And basically, both of them, we believe, is transformative, high-value product opportunity, very different in concept, but one, is our TransCon TLR 7/8, where we basically can provide a long-term exposure inter-tumor for weeks, months of an agent that can turn tumors from being basic unreactive to reactive. We believe that it’s a really paradigm shift and never been done before. What we’re doing with our bios IL-2, really believe that it’s going to be a best-in-class product opportunity.
Move both of them up both to a unique position as our 2 first most unbanked product opportunity in our oncology. That one is coming before the other one. It’s basically out from — the practical perspective is that we need to have a product opportunity being going to clinical operation, initiation of trials, filings and other elements like that. And we will have one coming end of this year and the other one will come around 6-months after. So there’s nothing that has changed for that. We are extremely exited on both of this product opportunity and continue to build up a unique pipeline in oncology.
Our next question comes from the line of Trevor Allred with Oppenheimer.
A couple for me. So following your recent capital raise, are you guys thinking about doing an M&A? And if so, what therapeutic category do you think you’re focusing on? And then also, are you hearing anything about the pace of enrollment that VISEN is having in China? And how do you expect that to translate to your other trials that you’re enrolling?
When we are having our portfolio review, we just had it here now on our oncology pipeline, we’re looking on this unique product opportunities we can build. We’re thinking about how we have built Ascendis Pharma to the stage we are today. We’re doing by the TransCon technology because we don’t believe that we have not seen other technology where we basically can make highly differentiated product opportunities, really addressing major unmet medical need, but still having a high success rate because the TransCon technology enables us to be in a position that we can work on validated target, validated parent drugs.
Why should we ever go away from that and starting to be like anyone else? We have a huge competitive edge with our TransCon technology, and we will continue to build on the algorithm that has proven so successful and because there is so many still low-hanging fruits that we can address. So I don’t expect us to see and move into any kind of M&A there. Related to how we are executing in other geographic region, for example, to our strategic investment in VISEN Pharmaceutical, I think they have a very highly talent company setup and they are working in the same standards as we do.
They are working with the same dedication. So I actually believe they are coming, and you will see the same kind of results coming out of their pipeline with our product, as you’ve seen coming out of Ascendis.
Okay. And any impact that you’re seeing from enrollment from COVID-related things with VISEN? And then do you see that translating — like those learnings translating to anything that you’re going to be doing with your initiations later this year?
I have to believe that if you look on the Greater China, I still think it’s one of the areas where it have less COVID-19 issues compared to other areas. And we have not seen any kind of a restriction after the first quarter in Greater China, how really to enroll the trials.
Thank you. There are no further questions in the queue. Ladies and gentlemen, this concludes today’s conference call. We thank you for participating. You may now disconnect. Everyone, have a great day.