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spk06: Good day and thank you for standing by. Welcome to the Q3 2021 Ascendus Pharma Earnings Conference Call. At this time, all participants are in the listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker for today, Mr. Scott Smith, Senior Vice President and Chief Financial Officer of Ascendus Pharma. Please go ahead, sir.
spk02: Thank you, operator. Thank you, everyone, for joining our conference call today. I'm Scott Smith, Chief Financial Officer of Ascendus. Joining me on today's call is Yen Mickelson, President and Chief Executive Officer, Esper Hoyland, Global Chief Commercial Officer, Dr. Dana Pizzuti, Head of Development Operations and Chief Medical Officer, and Dr. Yuha Punanen, 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 U.S. commercialization and continued development of Skytropha for the U.S. market, 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 U.S. market potential of Skytropha and our pipeline product candidates, and statements regarding our 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, 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 statement section in today's press release and the risk factor section of our most recent annual report on Form 20F. Skytropa was approved by the FDA in August 2021 for the treatment of pediatric patients one year and older who weigh at least 11.5 kilograms and have growth failure due to inadequate secretion of endogenous growth hormone. Otherwise, please note that our product candidates are investigational product candidates and not approved for commercial use. As investigational products, the safety and effectiveness of the product candidates have not been reviewed or approved by any regulatory agency. None of the statements made on the conference call regarding our product candidates shall be viewed as promotional. On today's call, we will discuss third quarter 2021 financial results and provide further business updates. 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.
spk01: Jan? Thanks, Scott, and good afternoon. Every quarter, I reflect on how the incentives team work together with patient and physician to satisfy major unmet medical needs. I also reflect upon the significant progress we have made toward our key development milestone to bring safe, highly differentiated product to patients as fast as possible. This quarter was special for Ascentis. It marks a defining moment for the company on our vision tree by tree part to achieving sustainable growth as a fully integrated eating global biopharma company. For years, we have worked to understand the biology behind growth hormone deficiency. We studied the science. We learned from previous successes and failures in trying to develop long-acting growth hormone therapies. And we were diligent in understanding the clinical data in pediatric and adult growth hormone deficiency. There have been very limited innovations since daily injection of recombinant human growth hormone were introduced over 30 years ago. And now, Ascendis has the first FDA-approved once-weekly product that offers pediatric growth hormone deficient patients caregivers and physicians what they have been seeking for decades. The approval of Transcon growth hormone in the U.S. is the culmination of determined efforts by the SENDIS team over many years to bring the first Transcon technology product all the way from the concept stage through non-clinical and clinical development. manufacturing and device development, and regulatory reviews so it can finally go out to the patients. With the approval of Skytrover in the U.S., we believe we have just begun to unlock the potential of what we are seeking to accomplish with the Transcon technology platform and algorithm for product innovation. To develop highly differentiated products addressing major unmet medical needs with expected high development success, a real paradigm shift. The same excitement we have for Transcon Growth Tomorrow exists across our entire portfolio of our five independent clinical product candidates. Why am I so optimistic? Because we believe the first FDA-approved product is a strong endorsement for the Transcon technology platform, our algorithm for product innovation, and Ascendi's infrastructure and expertise in product and device development. This is the reason why we are so enthusiastic about the prospect for our pipeline programs. Transcon PTAs and Transcon CMPs in endocrinology rare diseases, as well as our oncology programs, Transcon TLR78, Acronyst, and Transcon IL-2 Beta Gamma. We believe we have built a sustainable, robust pipeline and do not have the common challenge that many biopharma companies face in finding a second act to follow their first product as we, from the beginning, set out to build a sustainable pipeline in multi-therapeutic areas. Approval in the U.S. is a major success for Ascensis, but we will, of course, not stop there. We expect to receive European Commission approval of Transcon-Glutamone for Pediatric Glutamine Hormone Deficiency later this year or early next year. to report Phase III data for transcontinous PTH in adult hyperparathyroidism in Q1 2022, followed by a planned U.S. NDA filing in mid-2022. Our research and development engine continues to produce promising new product candidates, and we expect to continue the clinical development with additional regulatory submission. in rare disease, endocrinology, oncology, and also in our third therapeutic era. After we launched Skytrover in the US in mid-October, we quickly received our first commercial order and first commercial patient on therapy. The Ascendi's commercial team is executing on the long strategy, which is designed to the long-term value of our growth hormone product and laying the fundament for future product launches into the endocrinology rare disease area. We intend to create a global market-leading brand based on demonstrating clinical benefit and strong value proposition for patient, caregivers, healthcare providers, and payers. With Transcon Growth Hormone, we believe we can expand the global growth hormone market, while at the same time reducing the cost to society that results from suboptimal or lack of treatment. I'm often being asked about our pricing strategy and what do we mean by premium responsible pricing. Our health care economic outcome research demonstrates that with a premium responsible pricing, transplant growth hormone may deliver meaningful savings to the payer by potentially improving patient outcome compared to daily growth hormone. Our payer research covering 21,000 pediatric growth hormone deficient patients in the U.S. indicates only 20 to 30% of patients are adhering to daily injection therapy and therefore may experience suboptimal outcomes. With this in mind, We have established a VAC price for Skytropha in the U.S. that takes into account expected milligram per kilo dose difference for Skytropha compared to daily growth hormone in real-world practice. Also, on an annual basis, the VAC price is mid to high single percent higher compared to the leading daily growth hormone product. This is what we mean by premium responsible pricing and can be considered a win-win for patient, the caregivers, physician, including the society. We also understand the importance of U.S. market assets for patients and families, and we continue to work with payers to make Skytover as widely available as possible. Our priority is contracting based on the value of Skytover, rather than focusing just on volume. We are committed to building a long-term relationship with U.S. payers and health systems in the rest of the world as we are working to bring a portfolio of products to the market in the future. As we have highlighted before, Accenture's commercial leadership team is very experienced in endocrinology. especially in the growth hormone and PTH segment. They understand what it takes to create market leading brands. Our U.S. commercial organization is in place and we tend to cover around the 1,400 growth hormone prescribers. The pediatric growth hormone market in the U.S. is concentrated with about 80% of all prescription coming from about 20% of the prescribers. In parallel, Our experienced U.S. medical affairs team has been out in the field creating awareness with key opinion leaders and pediatric endocrinologists. A key component in the Skytrover launch in the U.S. has been the successful introduction of a SENTIS signature SS program. It has several different elements to it, but it is basically a personalized, Patient Support Program, with each patient assigning a nurse dedicated to working with them and their families, caregivers, and physicians from decision to treat to long-term therapy adherence. The program offers a suite of services including, but not limited to, prior authorization support, out-of-pocket assistance, and training on the Skytrover outrejector. As you know, at Ascendis, we always think globally. And so, let us turn now to our clinical development programs for growth hormone in other parts of the world. This week, the European Medicine Agency Committee for Medical Products for Human Use, or CHMP, has Transcon Growth Hormone on the agenda. We believe we are on track to obtain a positive CHMP opinion followed by an expected European Commission approval for transplant growth hormone by the end of the year or early next year. In Japan, we continue to screen and enroll patients in the 40-subject Phase III right trial for pediatric growth hormone deficiency, and in China, recent pharmaceuticals completed enrollment of its Phase III clinical trial of transplant growth hormone in children with growth hormone deficiency in March of this year. turning to potential label expansion for Transcon growth hormone. We also have the Global Phase III foresight trial underway for adult growth hormone deficiency. Looking ahead, we expect to conduct additional trials to support an application for labeling expansion beyond pediatric and adult growth hormone deficiency. Moving to Transcon PTAs. Our excitement continues around the clinical progress and prospect. Physician and patient story we have heard has so far indicated that Transcon PTAs has the potential ability to transform patients' lives. Given that 400,000 patients globally suffer from this and the lack of other treatment options, we believe Transcon PTAs, if approved, has the potential to be our largest endocrinology rare disease product opportunity. We think it could represent a market opportunity greater than 5 billion U.S. dollars. In September, we announced the 58-week bone mineral density data from the central lab reading in the Part 4 trial, the global phase 2 trial of transcon PTH in adult subjects These BMD data complement previous announced bone turnover data and demonstrated, as expected, continued normalization and stabilization of the BMD set score between 26 and 58 weeks. The BMD set scores parallel markers of bone turnover. which we believe is an indicator that the calcium metabolism subject in our Phase II trial are normalizing over time, as expected when PTH concentration is restored to physiological levels. We continue to have extremely high patient retention in the Open Label Extension Study, with 58 patients continuing in the trial as of November 7, 2021. I'm always so pleased when I hear about how many patients are remaining in the open-label extension study. This is the first time in my career that I have seen such strong patient commitment to taking a one-state injection and staying on therapy in an open-label study. We believe this is a potential indication of how transplant PTAs may be having a positive impact on short-term symptoms as to their quality of life. We believe that as BCH concentration is restored to physiological levels, it can improve short-term symptoms that could also translate into positive impact on long-term complications. We remain on track to report the 84-week Phase II data this quarter and would expect to see similar trends as we saw with the 58-week data. Globally, all three Phase III HB trials that are underway are progressing. Partway Japan, the Japanese Phase III trial, is designed to enroll a minimum of 12 HB subjects. Partway China, the Phase III trial in Greater China, has been initiated by decent pharmaceuticals. We are looking forward to reporting the top line phase two results from the North American and European trials in adult HP patients in Q1 2022. If positive, our plan is to file an NDA in the United States for Transcon PTH in mid 2022 for adult HP. The strong data we have generated so far reinforce our confidence in Transcon PTH as a potential first replacement hormone therapy in adult HP. Now turning to Transcon-CMP. We continue to move forward with two Phase II double-blinded placebo-controlled studies in children with achondroplasia. The first Phase II trial, the accomplished trial, is a dose escalation trial of 12 to 15 subjects in each cohort conducted mainly in North America, Australia, and Europe. The second one is the Accomplished China Trial, which is a cohort expansion trial of at least 66 subjects conducted in China. Completing two independent randomized placebo-controlled trials will give us 52-week clinical data on over 120 subjects with aconthoplasia treated with Transcon-CMP and over 25 subjects with placebo treatment. We believe these two blinded trials will be a strong indication of the potential safety and efficacy of Transcon-CMP. Later this quarter, we will provide a program update on Transcon-CMP, which will include a review of the biology and why we believe Transcon-CMP has a unique product profile that is highly differentiated from other treatments in development. We will provide an overview of the program involving the status of the dose escalation cohort, cohort expansion, and a safety update on the blinded data. We also plan to discuss target engagement to illustrate that Transcon CRP is doing what we expect it to do. And we will give an update on expected timelines for data next year. Now, moving to Oncology. We want to transform cancer therapy by improving a patient's endotumor outcomes by using Transcon systemic and endotumor technology. designed to provide sustained modulation of the tumor microenvironment and activating cytotoxic immunocells. We all know that developing effective and safe products has been a challenge within the oncology field. We believe by using the Transcon technologies and our algorithmic product innovation to turn on the body's anti-tumor immune system, we expect to improve patient outcomes. This is how we are looking forward to making a real difference in the way cancer is treated. Our oncology programs have made major advancement this year. For our Transcon TLR7 agonist program, we believe we have identified a product candidate that is highly differentiated compared to other product candidates by dramatically extending the duration of release of an active immunotherapy compound inside the tumor. With the Transcon technology, we are aiming to provide therapeutic efficacy inside the tumor for weeks and at the same time reducing systemic toxicity compared to what has been seen with direct injection of a parent drug alone into the tumor. We believe the prolonged activation of the immune system inside the tumor for weeks will also generate an ascorbic effect. killing similar tumor in other part of the body. Our Transcon IT 101 trial for Transcon TLR78 agonist in advanced cancer patient is ongoing. We have been dose escalating subject with Transcon TLR78 agonist in the monotherapy arm, and we have initiated dose escalation with checkpoint inhibitor in the combination arm during the third quarter. We expect to have initial results from the monotherapy dose escalation for Transcon TLR78 agonists by year end. We are presenting additional preclinical data for Transcon TLR78 agonists at the Society for Immunotherapy at our Chancellor's 36th Annual Meeting taking place in Washington, D.C. this week. Also in the third quarter, we submitted an ID to the U.S. FDA to initiate the Transcon IL-2 Beta Gamma clinical program. This is a Phase I-II clinical trial to evaluate Transcon IL-2 Beta Gamma in patients with advanced cancer. Transcon IL-2 Beta Gamma is a long-acting protocol using the same systemic Transcon technology as Transcon Gotamo. and is designed to improve cancer immunotherapy by providing long-acting exposure without a high Cmax of a highly potent IL-2 variant selected for the beta-gamma receptor. The second Oncology Clinical Stage product candidate is another sign of our commitment to solving unmet medical needs for patients by focusing on the science. IL-2 is a highly validated cytokine in the treatment of cancer. We have reviewed the data generated by others from the long list of IL-2 compounds, and we believe Transcontinental IL-2 Beta Gamma has the potential to be best in class and the first to fully solve the shortcomings of IL-2. Looking ahead to the rest of 2021, the fourth quarter is shaping up to be very difficult, with the potential to obtain a positive CHMP opinion, the program update for Transcon CMP, first patient data on Transcon TLR78 agonist, and our 84-week data on Transcon PTAs. We plan to announce the update for these R&D programs on a virtual research and development program update call in mid-December. We will provide additional details in the coming weeks. It was a great moment at Ascendis achieving our first product approval in the U.S. It is very rewarding that pediatric growth hormone patients in the U.S. now have a new once-weekly treatment option. What makes me even more happy is that I know we have the potential to help many more patients facing significant unmet medical needs. And as I said before, our goal at Ascendance has not just to get product approved, but to get products approved that can make a meaningful difference to patients, and not just once, but multiple times in multiple therapeutic areas. Now, let me turn the call over to Scott for a financial review before we open up for questions.
spk02: Thank you, Jan. Turning to our financial results for the quarter ended September 30, 2021, we reported a net loss of 80.3 million euro or 1.47 euro per basic and diluted share compared to a net loss of 121.7 million euro or 2.31 euro per basic and diluted share during the same period in 2020. Now let me run through some of the key components of these results. Research and development costs for the third quarter were 58.8 million Euro compared to 64.1 million Euro during the same period in 2020. The decline in R&D costs was driven by a one-time benefit to R&D costs. As a reminder, prior to FDA approval, we expensed pre-launch inventories of TransCon growth hormone as R&D costs. Upon FDA approval of Skytropha in Q3, 53.2 million euros was capitalized to inventory as raw materials and work in progress, resulting in this one-time benefit. Including this one-time item, the increase in R&D costs reflect continued advancement of our pipeline with the primary drivers including the following, an overall increase in personnel-related costs, And then for Transcon Growth Hormone, R&D costs were higher due to investments to expand our future manufacturing capacity, as well as increased clinical trial-related activities to support increased global clinical reach and label expansion. For Transcon PTH, R&D costs were higher primarily due to increased clinical trial-related spend, device development costs, and manufacturing costs, including the completion of multiple drug substance PPQ batches, as well as initial costs of building commercial inventory. For Transcon C&P, R&D costs were higher primarily due to increased manufacturing and clinical trial-related costs. And finally, for our oncology therapeutic area, R&D costs were higher due to increased manufacturing and clinical trial costs for Transcon TLR78 agonist and also due to increased manufacturing and preclinical costs for Transcon IL-2 Beta Gamma. Selling, general, and administrative expenses for the third quarter were 39.3 million euros compared to 17.5 million euro during the same period in 2020. These higher expenses primarily reflected increase in personnel-related and commercial expenses, as well as IT systems and other infrastructure costs as we prepared to launch Skytropa in the U.S. Finance income and expenses in the third quarter include a foreign exchange rate gain of 21.3 million euro, compared to a foreign exchange rate loss of 39.6 million euro in the third quarter of 2020, primarily related to translation of our U.S. dollar holdings of cash and marketable securities to euros. We ended the third quarter with cash, cash equivalents, and marketable securities totaling 929.9 million euros, which includes the net proceeds from our follow-on financing completed in September. As of September 30, 2021, the company had 56,877,723 ordinary shares outstanding. In November, subsequent to the end of the third quarter, we completed our previously announced $25 million share repurchase program in which we purchased 154,837 of our ADSs in the open market. Turning to an update on our U.S. launch of Skytropha for Pediatric GHD, The product is currently available in the U.S., and we have shipped multiple orders thus far into our specialty pharmacy and specialty distributor network for both initial prescriptions and channel inventory stocking. We are currently providing Skytropa for pediatric GHD patients through our dedicated patient support program known as the Ascendus Signature Access Program. Several insurance plans are providing initial coverage for Skytropa through the medical exceptions process. We're also in active discussions with U.S. commercial payers to broaden our access for 2022. And we are encouraged by the early enthusiasm surrounding the launch, and we look forward to updating you on our progress in the coming quarters. Turning to the remainder of 2021, key activities include, for Transcon HGH, execution of U.S. Skytropha commercial launch activities. investment in expanding commercial manufacturing capacity to support anticipated future demand, and continued execution in our ongoing Phase III clinical trials, including the Enlighten long-term extension trial and the RITE trial in Japan, both for pediatric GHD, and the Global Foresight trial in adult GHD. For Transcon PTH, key activities include continued execution of the Phase II Path Forward trial, which retains 58 subjects in the open-label extension, continued execution of the Phase III clinical program, including the Pathway trial and the Pathway Japan trial, and ongoing manufacturing of PPQ batches and initial activities to build commercial inventory. For Transcon C&P, key activities include ongoing manufacturing activities, including scaling up production, continued execution of our Phase II clinical program, which includes the two randomized double-blind placebo-controlled clinical trials in achondroplasia, the ongoing ACCOMPLISH trial, and the ACCOMPLISH China trial, which is being coordinated through Visa Pharmaceuticals. And lastly, in our oncology therapeutic area, key activities include continued execution of the TRANSCEND IT-101 trial for our TRANSCON TLR78 agonist and the IL-BELIEVE trial for TRANSCON IL-2 beta gamma. In addition to SCITROFA commercial launch activities in the U.S., We expect other SG&A activities will include TransCon PTH prelaunch activities and continued investments in personnel, systems, and infrastructure to support our rapidly progressing portfolio and growing organization. As Yen noted, we have a lot happening at Ascendus, so let me now also provide an update on our remaining corporate milestones and other disclosed events. For TransCon Growth Hormone, We continue to anticipate European Commission approval for pediatric GHD by early 2022, as well as completion of enrollment of the Foresight trial in adult GHD by Q1 2022. For Transcon PTH, we plan to provide an 84-week update for Path Forward later this quarter. We then expect to report top-line results from our Phase III pathway trial in the first quarter of 2022, followed by an expected NDA filing in the U.S. in mid-2022. For Transcon CMP, we plan to provide a clinical program update in December during the virtual R&D update, as Ian mentioned in his remarks. And finally, for Transcon TLR78 agonists, we plan to present initial monotherapy dose escalation data for the Transcend IT101 trial at our virtual R&D update. With that, operator, we are now ready to take questions.
spk06: Thank you. The floor is now open for questions. I would like to remind everyone In order to ask a question, you need to press star one on your telephone. Your first question comes from the line of Jessica Fay from JP Morgan. Your line is open.
spk08: Hey, guys. Good evening. Thanks for taking my questions. I have several, a couple commercial and a couple pipeline. First, the commercial questions. When you talk about playing the long game with your Skytropha strategy, Can you elaborate on what that means to you from a tactical standpoint? And second one on Skytropha is how should we think about the net price per patient for Skytropha? Appreciate the commentary on the relative list price, but will net price end up similar to or different from existing products? And then I got a couple pipeline follow-ups.
spk01: Thanks, Jess. Let me start, and then I can turn it over to Jesper later on. But first of all, when we think about Skype Fofa, we think about a best-in-class product opportunity, an opportunity that has not been available for the patient here in the U.S. for more than 30 years, even if I can count on multiple hands how many attempts there have been to develop. There have been products on the market, and they got taken away. We couldn't provide the same endocrine benefit that you could achieve with daily growth tomorrow. So when we saw the labeling without reflecting our clinical data, we are really, really thrilled to be in a position to provide such a benefit out to the patient, and not only the patient, the physician, the caregivers, but also the society. So from our perspective is when you have a best-in-class product opportunity, it's not to go out and be coming into panic. We want to grow the long-term value of this product. product opportunity because we believe it's so unique with the benefit it provides to the patient. And this is why we basically have defined what we call premium responsible pricing, which are basically providing us with a benefit on all aspects from us, but also to the patient, the physician, caregivers, and also the society. And this is what we're saying. And going back to your percentage, yes, we have a higher list price on VACs. but we're also utilizing much less material per patient. At the same time, we can then say that, yes, there is a benefit still for everyone. We want really to come out with for the patient also related to that. Then you can then say now from the tactical perspective is that, and Jesper can come into that, but I think it's related to Margaret says where he do the right negotiations with the right people in a right manner to really build up a leading bank with maximal value. Jesper, do you have more to comment on?
spk04: Yes. First, Jessica, I appreciate your question. On the tactical side, I can only say that we have hired in the team that has a deep knowledge into the growth hormone space. Everyone that works in the commercial team has a background in endocrinology. in growth hormone and all in PTH. Uh, everyone, all of them on the commercial frontline has won, uh, several circle of excellence, uh, events. And basically you can say we have taken the learnings that, uh, the team has had over the years and put it together and said, that's the best plan that we can come forward with. Uh, the ASAP program, the, uh, Ascentis program is truly standing out in the way that we're approaching the market and the commitments that we're having. So we are in process of implementing all the things, of course, in the middle of COVID and everything that's going on in the marketplace. But all in all, I feel very confident that we are on the right trajectory going forward. On the net price that you asked for, basically, as Jan is alluding to, And as you have also highlighted in your own survey on how we have set up the pricing, we have done it in a responsible way, but also certainly with a price premium. We are in a class of its own. We are not in the, you could say, the commodity market of once daily. We are truly the first in the once weekly segment, and we are going to segment ourselves into that because it's the area under the curve. account for us in terms of generating value for our investors and shareholders for the long term.
spk01: Thank you.
spk08: Great. And just a couple of pipeline questions, if I could. Have you dosed patients in the ACCOMPLISH China study? And if not, when do you think that'll happen? Is the plan still to use one dose in that expansion trial or could it be two dose levels? And to clarify, will we get timelines for data from these Phase II CNP trials at the December R&D day? And then switching to oncology, what type of single agent activity do you want to see for your IL-2 beta gamma in the All Believe trial to warrant moving forward?
spk01: That was a lot of questions, Jess. Going back to the start on the oncology related to that, First of all, let me take a situation. We have our research and development update from Oncology. It will be focused on the Transcon TLR78 agonist, and we expect at that event really to give you an update related to exactly what we believe that describes the uniqueness of this product opportunity with a complete different paradigm shift, how really to treat solid tumor by placing a compound inside the tumor that basically is being released over weeks and generate a monoactive environment. And I think that is the data you can look forward to see when we come to our December meeting. We will not present data from IL-2 beta gamma because we're first starting dosing a patient there. actually need to take a little bit more time before we basically give a program update to our I2 beta gamma. We expect dosing very soon of the first series of patients, and we're really, really thrilled about this unique product opportunity. Transcon's TMP, we will also provide you an update and basically give you all the answers to your question in December months. And it basically will illustrate really the highly potential of this highly differentiated product, Transcon CMP. And, you know, we have three different varices endocrinology products, and all of them are highly differentiated, each of them to anyone else you have seen before. And I'm quite sure we can give you all the data that's supporting that in the December meeting.
spk06: Great. Thank you. Your next question comes from the line of Michelle Gilson from Canaccord Genuity. Your line is open.
spk07: Hi, thank you for taking my questions. I guess the first one, just following up on Jess's questions on the launch, have you guys settled on what metrics you'll provide us to kind of track this launch and what should we be focused on in terms of what's most important for tracking the progress here. And then, you know, in your early discussions around the price, you know, can you give us a sense of, you know, what the feedback from payers has been so far and if they're recognizing, you know, the best in class profile and, you know, some of the other, you know, aspects or benefits that you described that justifies the premium responsible pricing? And then I have a couple on the pipeline as well.
spk01: I think we are coming to a stage where we are just initiating our loans now. We are about first in the beginning of the loans now. And we're feeling that we, as a responsible company, to give you clear guidance. We come out with guidance when we're feeling that we basically have followed the launch period in such a manner that we're feeling confident that we can give you clear direction about how this launch is going. What we're seeing and getting from the commercial team is I do not know how many KPIs there is on the launch. We follow them. All of them, I have to say, it's going far over my own expectation, which I actually always was high. So I'm feeling really, really confident. But when I see the team we have, I'm not in doubt that they are the best team I ever have worked with in the growth hormone market, and they will do it uniquely. So when we come into 2022, Michel, we will give you – when we're feeling we are in a position – that we're feeling confident that we can give you clear direction in what way it will go. But until now, I have been highly, highly positive, surprised about the feedback we have seen for our long strategy. But that also worked for a long time to get it ready. So I think that is basically the way you really build your success, being extremely well prepared with the right people.
spk07: Okay. And on the pipeline, I guess, for CMP in December, will you give us an update on, you know, what the path forward is for TransCon CMP in terms of kind of next studies and next steps for the program? And will we get an update on kind of what you're thinking in terms of potentially a phase three trial endpoint? I know that you're running a natural history study that will inform that. And then on PTH, you know, you mentioned, I think that this is the first time I've heard you on this call say that it's a $5 billion opportunity. You know, what are you looking to show in the phase three and, you know, maybe also from the phase two open label extension long-term data that, you know, would get you confident that you can realize that $5 billion opportunity.
spk01: Let me start on CMP first. What we would like to give you an update about the biology behind acondoplasia. And also how we explain a treatment with a continuous exposure of CMP will provide a complete different treatment regime compared to a short-acting CMP. Understanding that with BASIC will give you the idea why we believe a long-acting CMP concept providing a continuous exposure will basically change the treatment paradigm with CMP. And that is the biology we want to explain more and more to you. At the same time, we also would like to give you the uniqueness you see with such a compound that is continuous, be given in a flat, related to safety and target engagement, that basically are providing confidence about our entire understanding about the biology. We did exactly what we did with growth hormones. went down and studied and studied and studied and studied the biology of biocontamination, designed the target product profile that really addressed the unmet medical need there. And that is the learning that we would like to give you as we have provided for you why we believe how we can address old endocrine benefit with growth hormone, and we explained that for years and years. and we will start to do the same thing with how a sustainable exposure of CMP can provide a complete new treatment paradigm. And that is the understanding we would like to give you. So going back to PTHs, you ask me why I'm so confident, why I'm so bullish about PTHs. Because when we look on the 58 patients, look on all the demographic backgrounds, looking about if you are coming from different genetic diseases, from autoimmune, from post-surgery, going to look on AIDS, pill burden, and other things like that, we see a huge benefit for all the patients. So for all the clinical data we are accumulating and all the clinical data I have seen, I cannot come in and give you any kind of guidance except that all the patients we have been treating have seen a unique benefit of the patient. So from that perspective is, I believe all the patients that have chronic hyperparathyroidism, now we're addressing the adult segment, with about 80,000 to 100,000 in the U.S., much more in Europe. I have not seen any of them, not really, when we look on the clinical data, that not supporting that all of them will have a huge benefit. And that is not a small benefit. It's a benefit both to short-term, and we hope by accumulating further and further data, we also can see that we basically can benefit on the long-term risk for this patient group.
spk07: Okay. Thank you guys so much for taking my questions. Congrats on launching Skytropa.
spk02: Thanks, Michelle.
spk06: Your next question comes from the line of Josh Schemer from Evercore. Your line is open.
spk05: Hey, thanks for taking the questions. First on Skytropha, you mentioned several points are providing coverage. Can you provide some details in terms of what tier of copay and how many covered lives and where you expect that to be as you start 2022 and progress throughout the year? Second, you had mentioned starting trials to expand the Skytrofa label beyond pediatric and adult. What settings are you considering for those trials? And then last, for the PTH device and ultimately the CNP device, are they going to be similar to the Skytrofa device or will they be in any way different? Thank you.
spk01: Thanks. Let me start from the back because then I can still remember the things. The device we're using, for example, between Skytropha and basic or Transcon PTAs is a completely different device. Where we have in Skytropha single-use room temperature stability capsule where it's basic, has zero waste or anything like that, giving the optimal for the patient, for the caregiver, everything. You have room temperature stability. You use one cartridge every time you inject it, and then you basically have zero waste. It's optimal because growth hormone in some geographic regions are highly regulated. If you go over to PTH, we have implemented a system with our learning from diabetes, insulin pen, and other things like that, how you can have a pre-filled liquid formulation at room temperature that gives optimal confidence. And it's basically a multi-use pen device that looks very much like an insulin pen where you basically have dosing for about two weeks and then you start on a new pen. And we're basically providing three different pen strengths with basic titration in each single pen system. meaning is that we're going over and accepting, and what we're also seeing in our trials, that the patient needs to be optimized for each of them. So this is basically a completely different thing. For about CMP, as the last question, I think you need to wait what we're doing with CMP. This is still a lot of opportunities we're working on now, but what we always will have in the focus is the patient. What is optimal for the patient today? We did that for Grothamone. We're also doing that for hypopyrotary arrhythmia. Going back to then, I missed, I have still the Grothamone question. There was something between the Grothamone question. Okay.
spk05: It was formulary for Skytropha and then new indications for Skytropha.
spk01: New indication, you know, we have, and we are so lucky. just that we are a molecule that is designed by liberating the same unmodified somatopene you see in daily growth hormone, and you see also the same that is in doshas. So when we go to label expansion, we come with a complete different way to approach it, because we basically are in a position that we know now from growth hormone, pediatric growth hormone deficiency, how we basically are providing a unique treatment with all the same benefits that we have analyzed that you will see. So when we go to our adult trials, we will move to a different primary endpoint. We're not looking on growth velocity. We're looking about how we basically have a metabolic effect on truncal fat and other elements that basically is a metabolic effect dependent on the penetration out into the tissue of it. When we go to the long list, that is actually five, six different indications were globally approved, we are starting, and Dana can talk about this, where we're trying to find a new, elegant way how we basically can get as many as possible indications in the fewest possible trials but it's mainly being delivered out from the idea that we are in a position that we have a mode of action where the active ingredient is basically coming from somatopoeia. Dana, will you comment on it?
spk10: Well, yeah, Yen. I think one of the situations that we're in right now is that for the biologic, we need to sort of establish that our compound behaves the same way with these other indications as it does for pediatric hormone deficiency. And so we are in discussions with FDA about that. In addition, we are pursuing other sort of policy options that may enable sort of an expedited pathway for sort of a 505B2-like you know, filings for biologics. And, you know, that isn't available now. But, you know, the FDA has also recognized that that's a gap. And, you know, we are sort of working to try to facilitate getting language into the new PDUCA reauthorization, which will be signed next year. But in the meantime, we are going to be working very directly with FDA to work through in normal process, you know, how we can in an expedited way establish advocacy and the additional indications.
spk01: Just as we said before, we committed to make a global leading brand, and we know that it's really doing the right investment in the right tribes to support that we can build up this global brand. And that is what you will see be executed on in the future. We are not stopping before we're the leading global brand. This is our aspiration because we have the best-in-class product. Going back to your last question, and Jesper can help me coming in, but what I will say now, Jesper, as you said before, he's working on a strategy related to market assess, but we also see patients coming into, as I said in my part of this, my prepared remarks, that we're seeing patients being treated as a commercial patient today. But they're mainly coming up from the exception process and obvious exception process. This is patient which cannot really get the optimal treatment on daily growth hormone, which we have known for years and years. That's why it's being developed. And we see this kind of patient now being, actually getting approved for commercial patient to the exception process. Just give me the confidence that we did the right thing, really, to develop this product. Jesper, do you have further comments?
spk04: Yeah, I mean, Josh, it's still early days, but as you know, Skytropha is truly the first pediatric growth hormone coming onto the market, and we are in deep discussions with the PBMs of getting access, and we will announce, as they will, when we get access. And as you know, it's a little off-season, but we are certainly talking to them and discussing with them, and we are confident that we will be able to bring SkyTrofa to the patients. And as Jan said, for those we get in a situation where we get them off medical exceptions, we get that at full price, and that you have to bear in mind also when you look at what is the average selling price going to be for SkyTrofa, which is going to be a premium pricing.
spk01: Thanks a lot, Jesper.
spk05: Thanks so much.
spk06: Your next question comes from the line of Alethea Young from Kantar. Your line is open.
spk03: Alethea? Alethea? Sorry about that. Thanks for taking my question. I'll keep it tight here. I had no question. I wanted to ask about how... I'll just handle the blank piece of paper. I got you. So just a question on the potential commercialization in Europe. Just talk a little bit more about how those markets kind of compare, I guess, on a practical perspective around how patients are treated. We know their differences. So I just wanted you to talk about that kind of versus the United States And then we're going into oncology again. Have you guys kind of started thinking about it? I know you've thought about it, but are you kind of ready to give people kind of what the next maybe program or programs could be there, you know, in December? Thanks.
spk01: Yeah. You know, we are a European company. Ascentis Pharma is a European company. We know the European market extremely well. We have been working in the European market. So what we basically are building up, we're building up our strategy for Europe. And the element of that is because it's such a diverse group of reimbursement system you need to deal with. Some of them are fast, and sadly enough, most of them are slow. So for some countries, they can take up more than two years basically to get the right reimbursement. So what we're doing there, which I think is the key element I would like to give to you. We're building around a pipeline perspective. If you want to be successful in Europe, you cannot go with single product. I have seen European companies or US companies going to Europe and spending 100 million and gaining 5 to 8 million out in revenue. We are not going to do that. And this is why we have the knowledge of the European market We will be extremely responsible, but we still build up the European market in the way where we believe we create the best patient coverage, but at the same time also do it in a financially responsible manner. And we will, as soon as we're getting the expected approval in Europe of growth hormone, we will nearly at the same time having a readout of all phase 3 HPs, Well, basic will be the fundament for all European strategy. So you will see a strategy that is built on a pipeline approach, building on two hopeful established key product opportunity, Transcon Grotemo, Transcon PTH, and see how we basically penetrate it. PTH could be a huge, huge product in Europe because of the emphasis on long-term risk how really to have a patient population that basically could be in a position that could really benefit. And the value of avoiding long-term risk, I think, is much better recognized in the European setting, because as a stereotype saying is that 98% of all Germans stay in Germany the rest of their lives. Here, you move from one insurance company to the other insurance company, and it gives you a complete different aspect about how to build up high-value product opportunities, even on, you can say, a small, low-price level. And this is what you will see being implemented in our European strategy. I believe we have two paradigm shift compounds in oncology now. Transcon TLR78 agonist and our transplant IL-2 beta gamma. I think you will be thrilled to see the data that we will come out with here in the coming years for that. But as you said, we're not stopping there. We're still working on pipeline and building up the same strong pipeline we did in rare disease endocrinology with at least three product opportunities. So you will see in the coming years both new rare disease endocrinology products you will see more oncology product, and perhaps many of you will be very thrilled about the time when we come up with our new therapeutic area. We're still building everything on the same way we have been successful in rare disease endocrinology on the Transcon technology and our proven algorithm for product innovation, which really have shown how we can make highly differentiated product and at the same time to be successful. which I believe is a really true paradigm shift.
spk03: Awesome. Congrats.
spk06: The next question we have is from Joseph Schwartz from SVB Layering. Your line is open.
spk09: Hi, I'm Drury Dalyan for Joe. Thank you for taking our questions. Following up on a previous question on Skytropa, I know it's early days, but how should we think about the adoption of the treatment naive patients versus the exception process? Have your thoughts about the treatment naive patients versus which patients evolve now that you're in the market?
spk01: So after three to four weeks, you don't get new patients because just the diagnosis of a patient to be a true growth hormone deficient Patient takes time. It takes more than three or four weeks. So what you basically will see, you will see a different stage where, from obvious reason, if you have a patient that is not doing well on data growth hormone, it's already been diagnosed with growth hormone deficiency. All the paper, all the tests have been done. They're just not getting the right treatment outcome. What we will see later on is expected moving over to a more and more new patient because they go through the entire diagnostic pathway to get a confirmed diagnosis of being growth hormone deficient. And this is why you see a different state and that is what we expect to see in the coming months.
spk09: Okay, that's helpful. And my second question is on Transcon CMT. I understand that you're going to give us an overview of the biology behind the program and some kind of blinded analysis. I'm wondering, you know, are you doing this just for our benefit or, you know, why not just wait until both studies are done and unblind them both at the same time? And, you know, why is the study even blinded when the height trial of poor scitropho was an open-label study?
spk01: When we were running the Phase III trial of height, it was a blinded trial for one year or two. So our high trial was blinded, not placebo-controlled, daily growth hormone as a comparison. So the registration trial we had for SkyTropa here in the U.S. was one year blinded trial where we looked on the growth pattern for our growth hormone product. So it was also blinded. And the question you're raising is actually really, really interesting. Do we do it for you? Do we do it for us? No, I think we do it for the patients. We do it all from the perspective that we want you to give a comfort that we are progressing with a program that can give a meaningful difference for the patient. This is why we're doing it. At the same time, we can also give you the information why we believe we are highly differentiated to anything else. This is exactly why we're doing it.
spk09: Okay, thank you very much.
spk06: At this time, we will now be closing the Q&A session. This concludes today's conference call. Thank you all for joining. You may now disconnect.
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