Ascendis Pharma A/S

Ladies and gentlemen, thank you for standing by, and welcome to the first quarter 2021 Ascendance Pharma Earnings Conference Call. At this time, all participant lines 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 then one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star then zero. I would now like to hand the conference over to your host, Scott Smith, Senior Vice President and Chief Financial Officer at Ascendus Pharma. Please go ahead.

Thank you, Operator. Thank you, everyone, for joining our first quarter 2021 financial results 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, Dr. Mark Bach, Senior Vice President of Endocrine Medical Sciences, and Jesper Hoylen, Global Chief Commercial Officer, Dr. Dana Pizzuti, Head of Development Operations, and Dr. Juha Poonanen, 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 alluded 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 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. 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 statement section in today's press release and the risk factor section of our most recent annual report on Form 20F. Please note that our TransCon product candidates are investigational product candidates and are not approved for marketing by the U.S. Food and Drug Administration, European Medicines Agency, or other foreign regulatory authorities. As investigational products, the safety and effectiveness of the TransCon product candidates have not been reviewed or approved by any regulatory agency, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated. None of the statements made on the conference call regarding our TransCon product candidates shall be viewed as promotional and or product commercialization. On today's call, we will discuss our first quarter 2021 financial results and provide a business update. Following some prepared remarks, we will then open up the call to questions. I will now turn the call over to Jan Mikkelsen, our President and Chief Executive Officer. Jan?

Thanks, Scott, and good afternoon, everyone. Our goal at Ascentis is to create a leading biopharma company. by bringing highly differentiated product candidates addressing major unmet medical needs as fast and safely as possible to their patients. Beginning with our Transcon technology and algorithm for product innovation, we designed our Transcon Growth Hormone product candidate and developed it from idea stage through phase 3 pivotal trial. This year, we are seeing the results of our efforts as we are approaching the PDUFA date, June 25th for Transcon Road Hall. We held our late cycle meeting with FDA in April, in which FDA confirmed at that time that they are planned to meet the PDUFA action date. After the late cycle meeting, FDA conducted a BMU inspection at our Apollo Alto site over a six-day period with no 483 observation. Finally, we and our contract manufacturers have also submitted response to FDA's information request related to our contract manufacturing sites. We feel good about a potential U.S. approval for Transcon growth hormone for the treatment of pediatric growth hormone deficiency. We believe our ongoing labeling discussion with FDA are progressing well. Based on the latest feedback, we believe we will get a label that will support the scientific basis for Transcon growth hormone having a comparable mode of action to daily growth hormone. The great thing about retaining the same mode of action is that patients, physicians, and payers can rely on at least 30 years of scientific and clinical data to predict expected treatment results for overall endocrine health, including growth velocity. But getting an approval is just another important step in our plan to build a market-leading product. We are all aware of other long-acting growth hormone preparations that have been approved but not launched, or have been launched and then removed from the market. To have a market-leading product, We also have to provide a strong value proposition to patients, physicians, and payers. For patients, our once-weekly transplant gruptamol has in clinical trials shown safety, including hemogenic profile comparable to daily gruptamol. and superior outcome measured by analyzed high velocity in pediatric growth hormone deficiency compared to daily growth hormone. We believe our once-weekly Transcon growth hormone, administrated with an autoinjector in a room temperature stable presentation, will reduce the treatment burden for patients compared to daily growth hormone. For physicians, we believe our once-weekly transplant growth hormone may improve patient compliance compared to daily growth hormone, which potentially could lead to better outcome. And that physicians finally may have a growth hormone therapy for patients and caregivers that is associated with less treatment burden compared to daily growth hormone. Lastly for PEER, our recent US insurance claims and analysis data presented at ENDO 2021 demonstrated that the financial benefits of treating pediatric growth hormone deficient patients with growth hormone therapy and the dramatic need for improved adherence. We are continuing to execute on our global clinical reads and label expansion for Transcon growth hormone. In Europe, we expect a decision from the European Commission on our M&A for transcon growth hormone in the fourth quarter of this year. In Japan, we continue to execute on the phase 3 right trial for pediatric growth hormone deficiency. And in China, recent pharmaceuticals recently completed enrollment of his Phase III clinical trial of Transcon-Globetamone hormone in children with globetamone deficiency. We also have the global Phase III Foresight trial underway for adult globetamone deficiency to support label expansion for Transcon-Globetamone. And we continue to expect to complete enrollment of Foresight trial by late 2021 or early 2022. In summary, for Transcon Growth Hormone, we are aiming to bring a highly differentiated product to the patient. That can become a global leader in the growth hormone market and provide benefits to patients, physicians, and payers. Moving to Transcon PT8. We were excited about the 58-week results from the open-label extension of the phase 2 path forward trial in adult HP. Then we reported the 26-week data. We showed that we had a potential hormone replacement therapy that demonstrated normalization of serum calcium, normalization of phosphate, normalization of phosphate-calcium complex, normalization of urinary cancer. We also saw the major impact Transcon PTA treatment had on quality of life on the SF36 functional health survey. And we saw a trending towards normalization of skeletal remodeling. Coming to the 58-week results, the open-label extended trial is the first time to our notice that such a large group of HP patients has been exposed to physical levels of PTA for over a year. And it demonstrates how this treatment might help this patient group on a long-term basis. If I just sum up the 58 week results, what we saw was as expected. the durable response and well-tolerated safety profile that we have hoped for. All the elements of normalization of calcium metabolistic and homeostasis that we observed at the 26 weeks continued at 58 weeks, including normalization of 24-hour urinary calcium excretion. along with the initial rise of bone turnover followed by a decline trending to the mid-normal level. All this effect was observed in the absence of active vitamin D intake and the requirement for therapeutic intake of calcium supplements. What is remarkable and rewarding to me is that these 58 patients continue to participate in the Open Label Extension. I believe this is a reflection of the positive impact Transcon PTH is having on this patient's short-term symptoms and quality of life. I have never been part of a trial where we started with 59 patients and have 58 patients more than one year into an open-label extension. The patient demographic in our Phase II trial showed a very mixed population. Subjects suffering from post-surgical HP, idiopathic HP, autoimmune HP, some with kidney stones, renal insufficience. Some just recently diagnosed with HP and some with HP for more than 14 years. Some patients had mild pill burn and some had up to 8 grams of calcium supplement plus active vitamin D at baseline. Despite the wide variety of severity and disease background, 58 still continued in the open label extension. I believe the improvement in quality of life is driven by that. Looking at the adherence level, it was 99.8%, strongly suggesting that Transcon B PTAs is providing a benefit for the short-term symptom as the patient don't want to miss a shot. Everything I've seen with all the data suggests a patient benefit from Transcon B PTAs regardless of severity and disease background. We have seen that with the data, with the adherence, with the trial retention, and now we're also hearing the same message from the physician being part of the trial. Some physicians are now saying that all patients may benefit from Transcon PTH, not just because of biochemical controls, but because the patient's lives are improving. The patient can now become active again, can return to work. This is exactly why I see Transcon PTA addressing a major unmet medical need for the patient, but also for the society by enabling the patient to find active employment and work again. So when I look at the data, when I hear the stories from the patient, when I hear the stories from the physician, I feel so optimistic. I'm so hopeful that we really can help the more than 200,000 patients that are in the U.S., Europe, and Japan, and for the first time can potentially provide an hormone replacement therapy that normalizes their life for them. Not only based upon short-term symptoms, but also potentially on long-term complications. Later this year, in the fourth quarter, we expect to have the 84-week top-line OLE update from part forward. We also expect to report our top-line Phase III part-way trials results by the end of the year. We believe the data being generated supports a profile for Transcon PTA to be a potential first-line therapy for hypoparathyroidism. At the time of regulatory submission plan for the first half of 2022, we expect to have a solid data packet with both long-term 84-week data from our phase 2 part forward trial and 6-month randomized control data from the phase 3 part way trial. To achieve global clinical reach, earlier this month, we submitted a clinical trial notification to initiate a Phase III clinical trial, evaluating Transcon PTAs for adult HP in Japan. We look forward to sharing additional results later this year, as our goal is to make this important therapy available to HP patients worldwide as fast as possible. Turning to Transcon CMP, we are on track to provide an update on the clinical program in the fourth quarter of this year. As you know, we are conducting two randomized double-blinded placebo-controlled phase 2 trials in children aged 2 to 10. The first, the accomplished trial, is a dose-escalating trial of 12 to 15 subjects in each cohort conducted mainly in North America, Australia, and Europe. The second, run by Beeson Pharmaceutical, is the Accompanied China Trial, which is a cohort expansion trial of at least 60 subjects conducted in China. We are planning to keep the data blinded for one year for each cohort. Once completed, we will have a robust clinical data from two independent, randomized, double-blinded, placebo-controlled trials. To date, the safety is everything we have hoped for. There has been no injection site reaction and no indication of cardiovascular risk. Our top priority is to the acondalplasia patients in developing a safe and differentiated treatment option that address the comorbidity of the disease. Turning to oncology, we hit a major milestone late last year with our first IMD for our oncology division, which is also our first IMD delivering the Transcon hydrogel technology for sustained intertumoral delivery. We expect to initiate dose escalation in combination with a checkpoint inhibitor in July and to have initial results for monotherapy dose escalation for Transcon TLR78 agonist in the fourth quarter. For our second oncology program, we are on target to submit an R&D for Transcon IL-2 Beta-Gamma in the third quarter of 2021. Transcon IL-2 Beta-Gamma is designed for systemic administration via IV route and levers the Transcon systemic technology that you know from our endocrinology portfolio. As we are done in endocrinology, Our understanding of the biology has guided us in designing a compound with independently optimized receptor bias, potency, and pharmacokinetic to create that potential best-in-class IL-2 product. Summing up, starting with a product concept and now being less than one month away from our first VEDUFA action date, is a significant achievement. But as I mentioned when I started today's comments, we are not just trying to bring a product to a market. We are driving to solve major medical needs that we can meet by our Transcon technologies. We want to establish Ascendis as a fully integrated global biopharmaceutical company that has a portfolio of multiple independent products that make a difference in the life of patients. We have many important milestones to execute in 2021. I have never been more confident that we have the fundamentals in place to successfully building a leading biopharma company with multiple market-leading products in both endocrinology rare diseases and oncology. Now, let me turn the call over to Scott for a financial review before we open for questions. Thank you, Jan.