Ascendis Pharma A\/S (NASDAQ:ASND) Q3 2019 Earnings Conference Call - Final Transcript 2019-11-18T21:30:00+0000 Executives Scott T. Smith - Ascendis Pharma, Jan Mikkelsen - Ascendis Pharma, Juha Punnonen - Ascendis Pharma, Dana Pizzuti - Ascendis Pharma, Analysts Jessica Fye - JPMorgan, Alethia Young - Cantor Fitzgerald, Tazeen Ahmad - Bank of America Merrill Lynch, David Lebovic - Morgan Stanley, Michelle Gilson - Canaccord, Liana Moussatos - Wedbush Securities, Josh Schimmer - Evercore ISI, Joseph Schwartz - SVB Leerink, Adam Walsh - Stifel, Nick - Wells Fargo, Operator - Good day, ladies and gentlemen, and thank you for standing by. Welcome to the Third Quarter 2019 Ascendis Pharma Earnings Conference Call. [Operator Instructions]. Now, I would like to hand the conference over to our Senior Vice President and Chief Financial Officer, Mr. Scott Smith. Scott T. Smith - Ascendis Pharma Thank you, operator. Thank you everyone for joining our third quarter 2019 financial results conference call today. I'm Scott Smith, Chief Financial Officer of Ascendis. Joining me on today's call is Jan Mikkelsen, President and Chief Executive Officer; Tom Larson, Chief Commercial Officer; Juha Punnonen, Head of Oncology and Dr. Dana Pizzuti, Head of Development Operations. 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 that 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. 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 third 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 Mikkelsen, our President and Chief Executive Officer. Jan Mikkelsen - Ascendis Pharma Thanks a lot, Scott. Good afternoon, everyone. Thank you for joining us today. This quarter was marked by several milestone and achievements in our journey to build a leading, fully integrated, patient focused biopharma company. As outlined in our Vision 3x3. We are on track towards filing the TransCon growth hormone BLA in the US in the first half of 2020. And the MAA in Europe in the second half of 2020. We also advancing our two other endocrinology rare disease programs. For TransCon PTH, we announced last week an expansion of our phase 2 trial, which I will discuss in detail and the indicated as planned our TransCon P [Phonetic] phase 2 trial. We also continue to make progress with our clients through a status, global, clinical and commercial reach for our endocrinology rare disease pipeline. As our partner in China, VISEN Pharmaceuticals initiated a phase 3 trial for TransCon Growth Hormone for pediatric growth hormone deficiency. Let me start with an update on TransCon Growth Hormone. Preparation for our BLA filing in the first half of 2020 and MAA filing in the second half of 2020 are both on track. Last quarter, we discussed the two items remaining to be completed prior to filing. Finalization of our long-term safety data and completion of our PPQ manufacturing validation batches. As planned, in Q3, we reported the last subject visit for the long-term safety database consisting of around 300 subjects on trial of six months, 120 subjects for 12 months, 45 subjects for two years. We have also now completed the production of our top product validation batches required for regulatory filings. We are now finalizing the associated analytical and qualification reports for the BLA and MAA filings. Recently, the European Commission granted us Orphan Designation for TransCon Growth Hormone for pediatric growth hormone deficiency in Eurpoe. Orphan Designation is provided to therapeutic for certain health condition that affect a limit number of patient, and if a treatment already exist, the major thing must be of significant additional benefit. This is an early indication that the European health authorities recognize the unmet need in pediatric growth hormone deficiency and the clinical benefits of our once-weekly TransCon Growth Hormone therapy. In addition, in the US, in the enliGHten Trial around 150 patients have now successfully being transferred over to our intended commercial presentation of TransCon Growth Hormone consisting of our auto injector and dual-chamber cartridge. We believe this patient data will be sufficient to support our auto injector to be part of our initial BLA submission. In light of recent clinical development with other long-acting growth hormone products, I would like to address the fundamentals of growth hormone treatment. A successful product needs to have both the direct and indirect benefit of growth hormone to be safe and effective long-acting growth hormone therapy. We have stated for many years that the target product profile for a commercial successful long-acting growth hormone must have all the integrated benefits of daily growth hormone therapy. This benefit of growth hormone treatment include not only catch-up, sustained height velocity but also improved body composition, including fat mass and muscle BMI formalization, improved bone health, bone age advancement and improved quality of life. We believe, maintaining the same mode of action and tissue distribution as daily growth hormone is critical to mimic all these effect of native growth hormone. TransCon Growth Hormone is the only long-acting growth hormone product in clinical development that is based on the release of an unmodified human growth hormone. The same as in endorses somatropin. And somatropin used in daily growth hormone products. Our TransCon technology allows the released unmodified growth hormone to diffuse into the target tissue maximizing its ability to carve out the same effect as in [Indecipherable] or daily growth hormone. We are also developing our once-weekly TransCon Growth Hormone to have the optimal product features from the daily growth hormone products. We developed our auto-injector to build in optimal product features such as room temperature storage, small injection volume and a needle and an integrated connected healthcare platform also help clinician and our patient with a great adherence and convenience. We're also making good progress developing our connected healthcare support program. We expect this program to generate data to support adherence and include apps and interface point for both patient and provider at lungs [Phonetic]. We have advanced the TransCon Growth Hormone program from the idea stage all the way through clinical trials involving around 400 patients and we now on the threshold of submitting marketing applications. TransCon Growth Hormone has the potential not only to match the current daily standard but if approved, may in fact offer great high velocity outcome with TransCon PTH, we have followed the exact same development agreement designed to address a major unmet medical need. In hypoparathyroidism, patients are in urgent need of a therapy that sustained physiological levels of PTH 24 hours a day, seven days a week as a true replacement therapy. The burden of this disease is enormous. With current standard of care, patient and physician must balance the trade-off between managing short-term symptoms and reducing risk of long-term complication. The dilemma is that the treatment of short-term symptoms with calcium and activated vitamin D, at the same time also increase the long-term complications. Short-term symptoms have a significant impact on patient productivity and daily lives. In our Patient Experience Research, about 30% were no longer able to work and over 76 patient reported interference with work productivity. Meanwhile, the long-term complication add yet another layer of economic burden to the healthcare system. Complication include kidney failure at 4-fold to 8-fold greater risk with hospitalization or ER method experienced by 79% of patients. In recent months, this burden has been at the forefront of our minds, given the recall of the only approved PTH therapy for HP in the US, NATPARA. Since the September recall, we have been talking with sites and patient about their experience. Or recently, we saw that NATPARA might be back on the market and in patient's hands quickly. Then, at a recent patient conference hosted by the HypoPARAthyroidism Association, our team learned how the patient community has been significantly affected by this situation. We heard stories of desperation from patient faced with difficult choices about their care. Importantly, we also understood that it was uncertain when that short-acting PTH therapy may again be available for the patient. So we had been considering, what could we do to help some of this affected patient. While still advancing our clinical program as quickly as possible and conserving the robustness of our PaTH Forward clinical trial. Initial in PaTH Forward, we were planning to enroll subjects who were naive to PTH replacement therapy or who had undergone a long washout period of at least 12 weeks and a stabilization period. By putting the symptom in place, we are now able to include patient impacted by the recall with only minimal change to our plan timelines. We concluded this was the best course of action, we can take to address the patient need, by reducing the washout period and over enrolling the current phase 2 trial, we may now obtain data about the safety and efficacy of TransCon PTH in both PTH naive and experienced subjects. Depending on our final sample size of course the two groups, we can conduct various SWOT [Phonetic] analysis across their phase 2 trial endpoints. Including potentially informative data about the relative effects on bone turnover and bone health. We will also look at how the two groups perform during the long-term extension phase in 2020. Since the addendum will have no other impact on this sign or endpoints of the trial including no impact on the subjects outside of the US, it's also a relative stream that's already in process. Importantly, we will not be expanding the patient population in our phase 2 trial, if we did not believe TransCon PTH is functioning as designed as a true replacement therapy. In addition, one of the key element for the overall program is building the proper size safety database both in PTH naive and PTH experienced subjects. With a larger phase 2 trial, we believe, we are in good path to realize this objective. We are very confident in our decision in the potential of TransCon PTH and in the data to be generated from the expanded PaTH Forward Trial. We are very excited about the potential of TransCon PTH to change patients' life and look forward to the readout of the PaTH Forward Trial expected in Q1, 2020. Our third endocrinology product candidate TransCon CNP is also advancing by initiation of our phase 2 ACcomplisH Trial. With TransCon CNP, we again aiming to achieve the optimal balance of safety and efficacy. Upon exposure to the growth height. CNA -- CNP is both a modulator of growth and regulator of the FGR 3 pathway. In achondroplasia, CNP counterbalance the constant overactive signaling pathway caused by the mutation of the FGF receptor 3. Therefore, continuous exposure to CNP at effective level should result in normalization of the balance between the activity of the FGRF receptor 3 and the CNP signaling pathway. A balance that is essential for normal bone growth. CNP short half life in humans of two minutes to three minutes had made it impractical to maintain constant drug exposure from one administration to the next. With our TransCon technology, we have demonstrated that we can overcome this challenge, by providing continuous exposure to CNP for 24 hours a day, seven days a week, we believe we can develop TransCon CNP as a therapeutic option, not only for achondroplasia, but potentially, for various other growth disorder. Our phase 1 clinical trial of TransCon CNP demonstrated, we can achieve our target product profile. Now, we are evaluating TransCon CNP in the phase 2 ACcomplisH Trial. We have the aim to evaluate its safety and efficacy in around 60 subjects with achondroplasia from the eight years to 10 years. In this study, we are looking at a primary endpoint of annualized height velocity as well as other key secondary endpoints, which include changes in body proportionality , other comorbidities and patient-reported outcomes. Building from our phase 1 data, our goal is to demonstrate that once weekly TransCon CNP is not only height but the many comorbidities that can have a life-altering implication for children with achondroplasia. During the quarter, we also continue with our global ACHieve Study, our natural history started, which is now enrolling at around [Technical Issues] ACHieve will provide important insight in the experience of children with achondroplasia. Both the ACcomplisH and ACHieve clinical trials demonstrate our commitment to develop a new drug code [Phonetic] often for children with achondroplasia, one that is designed to improve the overall health and well being. In oncology, we recently presented data from our TransCon TLR7\/8 Agonist product candidate at the Society for Immunotherapy in Cancer. The data indicates potent antitumors effect in both injected and non-injected tumors. Perhaps more importantly, TransCon TLR7\/8 Agonist resulted in lower adoption [Phonetic] on systemic cytokines, when compared to unconjugated parent TLR7\/8 Agonist and triggered strong immunological memory when the animals were rechallenged two months later with a new tumor without any further treatment. We continue to advance several new and exciting program in this therapeutic area, including our receptor based [Phonetic] long-acting TransCon IL-2 beta gamma candidate. In this area, as planned, we are working towards our first oncology IND or equivalent filing in 2020. With our progressive step forward, we are one step closer towards achieving our Vision 3x3 of building a leading fully integrated biopharma company. Now, let me turn the call over to Scott for a financial update. Scott T. Smith - Ascendis Pharma Thanks a lot, Jan. Turning to our financial results for the three months ended September 30, 2019. Let me review some highlights. For the third quarter, we reported a net loss of EUR25.1 million or EUR0.53 per basic and diluted share compared to a net loss of EUR34 million or EUR0.81 per basic and diluted share during the same period in 2018. The third quarter 2019 net loss includes an unrealized non-cash gain of EUR27.4 million compared to an unrealized non-cash gain of EUR3.2 million in the 2018 quarter due to foreign currency exchange rate fluctuations. Research and development costs for the third quarter were EUR46.3 million compared to EUR31.5 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, then for TransCon Growth Hormone costs were higher, primarily due to increasing costs for manufacturing of validation batches and initial costs of building inventory in anticipation of a commercial launch which for now will be recognized as R&D costs when incurred. Declining clinical trial costs following the completion of our phase 3 heiGHt Trial. For TransCon PTH, costs were slightly lower, primarily due to a decline in the preclinical and in -- due to a decline in costs for preclinical research and manufacturing, which were partially offset by higher costs associated with our phase 2 PaTH Forward clinical Trial. For TransCon CNP, costs were slightly higher, primarily due to an increase in clinical trial costs related to our ACHieve Study and ACcomplisH Trial which were partially offset by lower manufacturing costs. Other R&D costs were higher, primarily reflecting activities within our oncology therapeutic area. As a reminder, our R&D expenses, including manufacturing-related expenses vary from quarter-to-quarter reflecting the timing of ongoing development activities. General and administrative expenses for the third quarter of 2019 were EUR10 million compared to EUR6.8 million during the 2018 period. These higher costs primarily reflect an increase in personnel and site costs as well as costs of building out commercial capabilities. We ended the third quarter with cash and cash equivalents of EUR658.7 million and 47,739,647 ordinary shares outstanding. As a reminder, our quarterly ending cash balance may be impacted by a combination of items, including exchange rate and working capital fluctuations, which this quarter led to a net positive impact on the ending cash balance. During the quarter, we continued to execute on our Vision 3x3 strategic road map, including completing our long-term clinical follow up and manufacturing of drug product PPQ batches for TransCon Growth Hormone and increasing our global reach through VISEN's initiation of a phase 3 trial of TransCon Growth Hormone in Greater China. And looking forward, over the near term, we plan to continue progress toward a BLA filing for TransCon Growth Hormone in the first half of next year and the MAA filing in Europe in the second half of next year. Continued growth of our endocrinology rare disease pipeline through label expansion of TransCon Growth Hormone into adult GHD and expansion of our phase 2 trial of TransCon PTH to include subjects previously treated with short-acting PTH. Report our topline phase 2 TransCon PTH data in Q1, 2020 and open label extension data for up to six months during 2020. Continue execution on the TransCon CNP ACcomplisH Trial as we march toward identifying an effective dose in 2020, advance our oncology product candidates toward first IND or equivalent filing in 2020 and continue increasing global reach for our endocrinology rare disease pipeline . Operator, we're now ready to take questions. Q & A Operator - Thank you. [Operator Instructions] And our first question is from Jessica Fye with JPMorgan. Please go ahead, your line is open. Jessica Fye - JPMorgan Hey guys, good afternoon. Thanks so much for taking my questions. First one is on manufacturing. I think you previously mentioned that you are expanding your manufacturing capacity in order to ensure you have enough drug supply for the launch. Can you just provide a little more of an update on the manufacturing progress and your confidence level that you have enough in place to be ready for the launch. Jan Mikkelsen - Ascendis Pharma Thanks, Jessica. What we're doing now is actually not really affecting our launch because we already have the capacity really to work and provide necessary material for entire launch space and we basic already are manifesting on the high-speed on every day. We really can do, just really to build up as much as possible TransCon Growth Hormone that can go out to the patients. What we more or less are really building up the secondary supplier is what we call the global reach, because we now really are implementing clinical trials for rest of the world to ensuring we not only addressing a US population but really expanding the TransCon Growth Hormone to be available basic on a global basis. And this is why, we are expanding the capacity and the capacity is build up in such a manner where we starting to get true, what I call the clinical operation, the clinical approval process for rest of the world. We will be in a position that we also have sufficient manufacturing capacity. So to make it very short, the expected capacity is not really mainly focused on the US market, is mainly build up to have global capacity. Jessica Fye - JPMorgan Okay. And then, I know, you recently got orphan drug designation in Europe for TransCon Growth Hormone and there has been some debate among investors about the regulatory requirements in Europe related to PEGylated products in children. So how much can we or can't we read into the orphan drug designation as kind of a good sign on that front. Did the European Commission review any data in granting that designation, or was it more just based on the market size and the potential for benefit over existing therapies without a specific read on the data? Jan Mikkelsen - Ascendis Pharma Sure. They're reviewing our data because we sending in application that describing the concept of our product compared to the clinical data we have achieved. From that perspective, I think, what we're recognizing is basic -- is that we are in a position that we really have a product opportunity that is really from an initial group, it also see it adding a benefit to the patient, and that is where we are, we are still in a continuous dialog with the European authorities. And just to recap that discussion is that we feeling pretty confident, we are coming as one of the first company at dedicated pediatric development plan, have always developed with this TransCon Growth Hormone as a pediatric product and what we have observed or what we have seen is giving a high confidence that we really have a product opportunity that have a global reach. Just recall, we have been through the entire preclinical package both in Japan, South Korea and China and work out any kind of push back to all preclinical package. Jessica Fye - JPMorgan Okay and last one from me, can you guys talk about the changes at the SVP level including Jonathan Leff's departure, are you guys looking for a new CMO at this time? Jan Mikkelsen - Ascendis Pharma We are from a company politic, never comment on single position and single cases and what we are doing is that we were in a position that Jonathan has left the Company for months ago and we are in a position, where we have dedicated a lot of the operation part to three different areas and is really function extremely well, and we have high level of confident that we now are developing an organization that really can support that we can implement our Vision 3x3. And I'd say, that is really the highly effective thing we want to do and there has not been any kind of change in timelines or anything -- about what we have done in the last 18 months is basic after we implemented our Vision 3x3. We are now in trying to develop the organization. So the organization also can be developed to a state that it can support and successful implementation of our Vision 3x3, and this is what we're doing in a strategic manner to ensure that can be successful as we want to be. Operator - Thank you. [Operator Instruction] And our next question is from Alethia Young with Cantor Fitzgerald. Please go ahead. Alethia Young - Cantor Fitzgerald Hey guys, thanks for taking my question. I was just curious about maybe digging a little bit more into maybe how opportunistically think about the PTH kind of pathway. If you were able to get some patients who had seen that far in the past. And I have -- and the follow-up is, of the 70,000 patients in the United States or so. I mean, how many do you really think is kind of at need, if we're trying to kind of think about an addressable market size here.Thanks a lot. Jan Mikkelsen - Ascendis Pharma That was a lot of questions. Alethia Young - Cantor Fitzgerald There was only two. Jan Mikkelsen - Ascendis Pharma That was a lot of question. So let me try to take the question in different stages and if I miss any one of them, please come back. So let me first take the patient population. I think, we have it, very, very clearly in our Investor Day, how many patient we believe to have HP in -- in US. And you think it's about 70,000 to 100,000 [Phonetic]. But I think really what the issue is -- is the dilemma, the physician are in -- the patient are in because both have an issue with short-term symptom, long term complication and better -- better you control the short-term symptom, you basic worsen the long-term complication. So therefore, you can have a patient that basic feeling, I deal some way with my disease, but then that basic worsening the long-term complication, there is no win here. And from my perspective is I personally believe that the majority of this patient should really be on treatment when there is a true replacement therapy. And how many will be there? I think there is always a good discussion, but I think out from a patient focus, I believe the majority should be on this treatment here. So coming back to some of the other thing about NATPARA, where we saw the element coming out with desperation. And just recall, NATPARA is a compound that basic or not is a true replacement therapy. And even with that, what you can call a compound that's providing some benefit, we really saw a basic desperation by the recall of this product. For me, its really illustrate again and again, we really addressing a major unmet medical need and we will stay focused and focus on how fast can we get the TransCon PTH out to the patient, and this is what we took this initiative is to say, we want also to show that basic and you can say, in a switch therapy, switching for patient that coming nearly off NATPARA transfer them over to the product. We also see the same kind of benefit that we receive more in a naive patient population. Alethia Young - Cantor Fitzgerald Great, thanks. Operator - Thank you. Our next question comes from Tazeen Ahmad. Your line is open. Please go ahead. Tazeen Ahmad - Bank of America Merrill Lynch Hi, good afternoon. And thanks for taking my question. Yeah, I just wanted to get your thoughts on the bit of the update that BioMarin provided for, I'd say, achondroplasia drug, obviously you're waiting for their pivotal results to readout, but would be interested in hearing your thoughts about what kind of read through, we should expect for your product. Just given the similar mechanisms. Thanks. Jan Mikkelsen - Ascendis Pharma Thanks, Tazeen. I actually think, we agree a lot with BioMarin. The CNP is absolutely the optimal way to address this condition of disease and potential many other areas. Where we some way, have a different idea and this is actually going back to answer your question. If you have a hyperactive signaling pathway 24 hours, 7 days a week. How can you really in a meaningful way balance this pathway, no -- back to a normal level by only having drug exposure for two hours to three hours. Basic saying is that 10% of the time you have an active drug. This is why, we believe when we designed our target product profile that we need to have a continuous exposure. It will be like taking a diabetic drugs only for two hours to three hours, no one wants to do that. They want to have a continuous exposure of a basal insulin. And this is where we basic want to be in a position that we can provide a continuous exposure and we know from basic growth hormone market, how difficult it is to provide really optimally, hearings on any kind of patient group in a pediatric with daily injection. And this is why we also designed it as a once-weekly dosing, and that is exactly, where we believe, we are highly differentiated towards BioMarine product. So I hope for the patients. I hope there will be some clinical effect on it and I think, this is what we -- everyone is waiting forward to see later this quarter. Tazeen Ahmad - Bank of America Merrill Lynch Okay and can you just remind us when your next data update is for your program in CNP? Jan Mikkelsen - Ascendis Pharma You asking me a question, which I really can't answer because I really do not know exactly when we hitting the effective cohort. We believe, we will reach it in some of the first cohort but exactly, when we getting that, it's really, I cannot really give you any kind of forward-looking statement relating to. Operator - And our next question comes from David Lebovic with Morgan Stanley. Please go ahead. David Lebovic - Morgan Stanley Thank you very much for taking my question. First question. You do have the dimension, how many patients you were ultimately expanding the phase 2 PTH trial to and how ultimately would that analysis of the separate patent populations look. Jan Mikkelsen - Ascendis Pharma Thanks, David. I think, we need to separate it in different kind of endpoint, because when we look at the primary endpoint, normalization of calcium, withdrawal of activated Vitamin D, withdrawing of calcium supplement, normalization of urinary calcium, I don't think that will have any kind of effect where the patient is coming from. But if you look an element like for example, on a long-term extension data, where you think about bone quality, bone density, we know that a new HP patient because of lack of bone turnover, basic is building up a much higher bone density than a normal person. That happen not because it's really -- is a positive thing, because what they do is lack the normal bone turnover, so you basic -- are building up old bone. And this is where we would potentially see an development that is where different in bone density from a person that have been on a highly -- product like a short acting product like NATPARA or Forteo with a basic is also at osteoporosis drug and therefore, you will see that coming from a complete different bone density structure. And this is where, you will segregate that analysis on the primary endpoint, no difference, but when we go to element like bone density on other related bone thing , you basic, I believe we will see a different from the two different group as to why we prepare to make SWOT analysis of this. David Lebovic - Morgan Stanley That makes sense. So will they ultimately be about 40 patients in each site total? Jan Mikkelsen - Ascendis Pharma What we are trying to aim, because we already have randomized large portion of patients. We couldn't change our block randomization and in the block randomization, we had a ceiling on 64 patients. So from that perspective, we are in a position is that, it's very, very hard for us to move higher up than around 60, because we -- it's too high burden to start to really do the entire randomization. So from that perspective, we will -- believe that we hope to have about 40 naive patient, which we are on track to enroll and then, with 20 patient on previous treated with NATPARA. David Lebovic - Morgan Stanley Thanks for taking my question. Operator - Thank you. Our next question comes from Michelle Gilson with Canaccord. Please go ahead. Michelle Gilson - Canaccord Hi. Thank you for taking my question. I was just hoping, you could perhaps elaborate a bit on how the clinical profile of a typical NATPARA patient, where at this point of previously on NATPARA patient differs from recombinant PTH naive patients, perhaps beyond bone turnover and if you think, things like, like the higher amount of supplement that these patients might be on might offset the phase 2 results. And then should we be expecting the reduced washout period to complicate the supplement titration or how patient should respond to TransCon PTH in anyway. Jan Mikkelsen - Ascendis Pharma To exactly why we limited down to four weeks because we believe and I think, data showing that after you have stopped NATPARA for four week, we actually are in a position, where we both had dealt with Hungry Bone Syndrome and other things like that. So we basic are stabilizing, you can say, the same calcium with supplements in a level, where it's really, really are much more reflecting that is basic will be coming into study related to the primary endpoint exactly as the more naive patient. Michelle Gilson - Canaccord Okay. And then can you just after you get the results from the phase 2 study. Can you just talk about timelines for initiating the phase 3 and is -- is this phase 2 change affects the way that you think about that phase 3 and then really for TransCon PTH? Jan Mikkelsen - Ascendis Pharma I think for us, it's really, really, really important to have the two patient group now and what are the thing we also are really excited about in sometime next years both have six months data, where really, really is this in large patient population. So apart from related to the phase 3 design, what we missing on for example the six point endpoint is exactly the same thing we also will be measuring in the primary endpoint on our phase 3 trial. So accessing that is not changing anything. We are utilizing the same primary endpoint that we have agreed with regulatory agencies for as an indication for both our phase 3 trial and we are also testing them in the extension study. Michelle Gilson - Canaccord All right, thank you. Operator - Thank you. Our next question comes from Liana Moussatos with Wedbush Securities. Please go ahead. Liana Moussatos - Wedbush Securities Thank you for taking my question. What are the steps to filing the IND for the oncology program? Jan Mikkelsen - Ascendis Pharma That is a good question. Where we are in a situation, where the basic are finalizing the CMC upscaling to make GMP material and we are finalizing and working on our preclinical safety packet that is the normal safety packet that will be part of the IND or equivalent filing. Perhaps, Juha, you will say something on. We are really excited to go out and showing our data here in for first time in a setting, where we really get out and representing a complete new concept of having long-term intra-tumor delivery, and Juha, perhaps you can talk a little bit about the excitement that was showing from this post presentation. Juha Punnonen - Ascendis Pharma Right. Yes. And regarding the IND enabling studies, it really is a very standard package for safety and GMP manufacturing, nothing unusual there. We're very excited by the programs. There is a lot of potential in multiple indications and looking forward to the IND filing by the end of the next -- end of next year. Liana Moussatos - Wedbush Securities Thank you. Operator - Thank you. Our next question is from Josh Schimmer with Evercore ISI. Please go ahead. Josh Schimmer - Evercore ISI Great. Thanks for taking the question. Jan, in your prepared remarks, you indicated that you had plans to evaluate the TransCon CNP and settings beyond achondroplasia. Can you give us a sense of timelines to start some of those trials and what the development program might look like? Will you be pursuing the basket approved similar to what BioMarin discussed on their analyst event? Are you going to target individual, short stature indication separately? Thanks. Jan Mikkelsen - Ascendis Pharma Yes, this is actually some plan, we really, really are developing a lot now. We have a complete list of lot of interesting indication, where we really see huge unmet medical need that we really, really can address, not only in growth disorder, but it could also be in potential outside growth disorder. I think CNP from my view, it's one of the most interesting new discovery pathway, where you really can see how we can affect a lot of diseases. But going back to growth disorder, I could think that potential CNP would be exactly be a cornerstone in many growth disorder as you have growth hormone being cornerstone today. And potentially, you can also see indication where both of them will be used in combination to get the optimal efficacy. And it was why, it was extremely important for us to have really both of them as a once-weekly product and potentially have the opportunity to also make combination therapy. So what you will see later this next year, you will basically see our plans being disclosed about what kind of indication, we want to go in and what and when we going to do it, but just, I think, I'm seeing, we really going in very broadly with this compound. We will like to see some of the first cohorts now. And then when we have seeing that we basically have a strong idea, where to position it. Josh Schimmer - Evercore ISI And for the TransCon PTH program, what do you ultimately see as the gating steps for approval and how, where are you in terms of CMCN's [Phonetic] characterization and stability testing and is it more likely to be long-term safety generation that determines the timing of the potential filing. Thank you. Jan Mikkelsen - Ascendis Pharma I think, two elements, were different compared to the growth hormone. One element, it's very, very different for what we did the growth hormone already in the phase 2, we using the commercial presentation, which are major, major difference. Basic, phase 2 are being conducted with the commercial presentation we are going to market with. So we are not somebody who need to bridge or anything that that is already status. Now, the second thing is that we are executing on the validation batches on high speeds. We have it up in full scale, we already had in the scale, we want to go from into our phase 2 material so also because the need for the material is so much, much, less in this. The third element is that we filing on an NDA instead of BLA, meaning is that basic, the validation and PPQ batches don't need to be finalized at the day of filing. But you need to have a justification of the process validation at that time. So we are in a much, much small pool situation compared to the TransCon PTH that we ever have been compared to the growth hormone. PTH is also much, much, much simpler to synthesize and produce because it's done by chemical synthesis instead of a biological manufacturing. Josh Schimmer - Evercore ISI Got it. Thanks very much. Operator - Thank you. Our next question comes from Joseph Schwartz with SVB Leerin. Please go ahead. Joseph Schwartz - SVB Leerink Great, thanks very much. So I noticed that the primary endpoint for the PaTH Forward Trial is evaluated at four weeks, but it seems to have taken much longer for NATPARA to work on some of the endpoints, you're evaluating. So can you give us a sense of the time course that you expect and whether the time will be adequate and which of the endpoints, do you think would be more or less challenging to achieve. Jan Mikkelsen - Ascendis Pharma I think, the main huge difference between NATPARA and what we're doing is that you should much more compare to what you see with an infusion pump, where you providing PTH 1-34 in infusion pump. What can you do with infusion pump study today?You can withdraw all the supplement basic on day zero. Could I do that in the past? No. We were titrating forever, ever, weeks for, weeks for, weeks for, weeks. So what we believe that we need about six days to eight days to come to a steady state of PTH level and we believe after six days to eight days, we have really, really mimic what you do with the infusion pump. So when we come to six days to eight days, we basically should be in a position that we can do all withdrawal of all the supplements. And that is a huge, huge step on what you solve with NATPARA. Joseph Schwartz - SVB Leerink Okay. And then as you look at the market for TransCon hGH, what percent of treaters are sophisticated enough to figure out how to titrate TransCon hGH dosage in patients switching from daily growth hormone in order to keep IGF levels under the threshold of two or three standard deviations. I ask because a lot of the physicians, we speak with at academic sites describe themselves as IGF people, who are comfortable that they can push on this growth accelerator pedal appropriately, but they acknowledge that there may be community sites who are less adept. So have you look at the marketplace, and thinking about who would be ready to adapt TransCon hGH, what do you see? Jan Mikkelsen - Ascendis Pharma I should think that what we have done, we have done an extensive survey, about 120 endocrinologists and we asking exactly all these different question. And sure, we're seeing exactly the same thing, you're seeing, a difference between the academic centers and all at once, this is really 100% right. But what we also know that all the patient that -- all the physician that used to use daily growth hormone. And, you know, that TransCon Growth Hormone luckily can be as easily titrated as daily growth hormone. The only difference we need to have to measuring average IGF-1, we need to measure that on day five, and if measured outside day five, that is an correlation factor that correlated back to an average IGF-1. So all the knowledge, all the thinking about how to titrating, you can do exactly the same thing with TransCon Growth Hormone, because we have the same unmodified compound as daily growth hormone and basic, at the same mode of action and but already even that. So all the learning for the last 20 years, 30 years, you can basic transfer or to TransCon Growth Hormone only main difference, you need to measure at day five, where you get the average IGF-1. Joseph Schwartz - SVB Leerink So is that -- does that entail additional monitoring, or is it the same amount of monitoring is currently applied to the data. Jan Mikkelsen - Ascendis Pharma It will be -- we believe, it will be the same kind of monitoring and it will not be more or less restrictive. Only thing is that you need to have a correlation factor, if you measure it not on day five but on other days and this correlation factor will transfer you over to an average IGF-1, which are exactly what were used to apply in this. Joseph Schwartz - SVB Leerink Got it. Thank you. Operator - Thank you. Our next question is from Adam Walsh with Stifel. Please go ahead. Adam Walsh - Stifel Hey guys, thanks for taking my questions. On the PTH PaTH Forward, now that you've increased the enrollment with the NATPARA patients, your guidance previously had been to not expect any kind of statistical outcome, should we get our hopes up there with the trial expansion and then are we still on for starting a growth hormone trial next year, and I'm going to sneak one final one in here on -- on the achondroplasia, if vosoritide gets approved. What do you think that means for enrollment for your future trials? How should we think about that? Thank you. Jan Mikkelsen - Ascendis Pharma I got three different questions. I think, Adam, if I got it all, right. Adam Walsh - Stifel Yes. Jan Mikkelsen - Ascendis Pharma The first question is really very, very, very, simple. It's clear no. I think, this is -- expansion has not anything to do with statistic power. I actually think we can achieve the statistic power we want to do with much less than the 40 patients. So it's nothing to do with that. We pretty confident this product will function as a true replacement therapy. Next year. Yes, we will plan for additional label expansion of our TransCon Growth Hormone and we're working dedicated for that to achieve. The last one on vosoritide. I could believe, every parents, every child should be treated with the optimal product. And I think, this is typical of what we also see in all indications and I think and I hope, we really would be in a position that we can provide an optimal treatment for patients with achondroplasia that is not just giving a small height improvement of potential one centimeter to two centimeter but really can be in position that really also can address the real comorbidity of this condition or disease. Because, they don't have all the comorbidity just because of heights. They have lot of other elements that we would like to address. Operator - And our next question is from Jim Birchenough with Wells Fargo Securities, please go ahead. Nick - Wells Fargo Good afternoon, it's Nick on for Jim this afternoon. With the NATPARA outage, if it continues, is there -- maybe discuss the regulators' opportunity to get a more rapid product to table for TransCon PTH? Jan Mikkelsen - Ascendis Pharma We are coming from that position that we want to really show it in the patients and that is what, we're going to do now, and this is why, we have expanded the trial also through that. What we always hope that we can be in a positive dialogue with regulatory agencies and be in a position that we potentially can help this patient group in the best possible manner. And this is what we dedicated to do and this is why, we're doing this change in this way. Dana, do you have any comments? Dana Pizzuti - Ascendis Pharma Yeah, I think, our plan is as soon as the data are available that we would intend to show those to the regulatory agencies and assuming, they come out the way we think they will, we are fairly confident that they will help us to expedite the program. Until the data come out, we can't be any more explicit than that. Nick - Wells Fargo So, and then just a follow-up on that. Is the linker chemistry for the TransCon loyalty, the same the PTH that you can borrow or walk at the data you've already developed for growth hormone? Jan Mikkelsen - Ascendis Pharma The entire concept of the TransCon technologies is they're almost identical across both the growth hormone PTH and CNP. So definitely, there's a lot -- a lot of learning from the different places. I also believe that when we saw that in TransCon CNP, we basically got the opportunity to move down to children of the age two in our initial phase 2, I think, it's just building on a great knowledge about the safety of the TransCon technology. Operator - [Operator Closing Remarks] Jan Mikkelsen - Ascendis Pharma Thanks a lot. Scott T. Smith - Ascendis Pharma Thanks a lot everyone.