Ascendis Pharma A/S

Good day, and thank you for standing by. Welcome to the Q4 2021 Ascended Pharma Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during that session, you will need to press star 1 on your telephone. Please be advised that today's conference is recorded, and if you require any assistance during the call, please press star 0. I would now like to hand the conference over to your speaker today, Mr. Tim Lee, Senior Director of Investor Relations. Tim Lee, the floor is yours.

Thank you, Operator. Thank you, everyone, for joining our full year 2021 Financial Results Conference call today. I'm Tim Lee, Senior Director, Investor Relations of Ascendus Pharma. Joining me on today's call is Jen Mickelson, President and Chief Executive Officer, Scott Smith, Senior Vice President and Chief Financial Officer, Jesper Hoyland, Global Chief Commercial Officer, Dr. Dana Pizzutti, Head of Development Operations and Chief Medical Officer, Dr. Juha Purnanen, Head of Oncology, and Dr. Steena Singhal, Head of Clinical Development 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 statement may include but are not limited to our U.S. commercialization and continued development of SCICROFA 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 for 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 and 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 our forward-looking statements section in today's press release and the risk factor section of our most recent annual report on Form 20F. Krantz-Kahn Human Growth Hormone, or Krantz-Kahn HGH, is approved by the FDA in the U.S. under the brand name Skytropa for the treatment of pediatric patients one year or older who weigh at least 11.5 kilograms and have growth failure due to inadequate secretion of endogenous growth hormone. In addition, the European Commission has granted a marketing authorization for Lonepeck Somatropin Ascendus Pharma, developed under the name Transcon HGH as a once-weekly subcutaneous injection for the treatment of children and adolescents ages 3 to 18 years with growth failure due to insufficient secretion of endogenous growth hormone. In general, we refer to this product as Transcon HGH unless we are referring to the product in the context of a particular jurisdiction such as the United States or the European Union. Skycopa was approved by the FDA in August 2021 for the treatment of pediatric patients one year 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'll discuss our full year 2021 financial results and provide further business updates. Following some prepared remarks, we'll then open up the call for questions. I will now turn the call over to Yen Mickelson, President and Chief Executive Officer.

Thanks, Tim, and good afternoon. 2021 was an extraordinary year for Ascentis. The regulatory approvals of Transcon growth hormone in the U.S. and Europe were a key milestone in achieving our vision 3x3. The approvals of Transcon growth hormone in the U.S. and Europe were a validation of the Transcon technology platform, validation of our algorithm for product innovation, and validation of our infrastructure and capabilities to achieve approvals in the US and Europe of a combination product, including biological manufacturing. We believe these successes confirm that we have the right strategy. and the people and capabilities in place to achieve our vision three by three and to build a sustainable, profitable, leading global biopharma company. But we didn't stop here. In 2021, we also realized significant advances in other areas essential to our vision three by three. These include embedding important studies for TransCon PTAs program in adult hypoparathyroidism and progressing our TransCon CMP program in acondyloplasia. Both of the programs are essential to our goal of achieving regulatory approvals for three independent endocrinology rare disease products. To achieve our goal of global market leadership for each of our products, we continue expanding our global clinical groups and label expansion in the endocrinology rare disease space this year. In our second therapeutic era, oncology, we have two highly differentiated cancer immunotherapy programs being advanced through clinical development. We believe we can transform the treatment in immuno-oncology with our products. Lastly, for our third independent therapeutic area, we are conducting research using our Transcon technologies. and the essential algorithm for product innovation to create a pipeline of independent product candidates addressing major unmet medical needs. As for all our established product candidates, we have the same high expectation for each of the product candidates in our third therapeutic era to achieve global leadership, and create a multi-billion dollar product opportunity. A key element in our vision 3x3 is sustainable growth. We intend to continue developing new product candidates using the Transcon technologies and the Ascenius algorithm for product innovation. We plan to continue to build our organization capability with the aim to bring safe, highly differentiated products to patients as quickly as possible across multiple therapeutic areas, indication, and geographies. I expect that 2022 will be another unforgettable year. You can expect us to share data and regulatory milestones across our five independent clinical programs throughout the year that demonstrate solid progress towards long-term growth. Equally important, we plan to provide you with updates related to the commercial launch of SCARTOFA in the U.S. and the planned launch for commercialization in Europe. as we expand access to this important treatment option for pediatric growth hormone deficiency. In the era of growth hormone, we are here to build a leading global brand. Today, Skytropha is the only approved one-sweep growth hormone on the U.S. market. In the four short months since its launch, our commercial teams have leveraged their decades of endocrinology experience and relationship to meet the target prescribers, maximize awareness of sclerotopia through multiple channels and events, and provide patient treatment and support through our Ascendi Signature Access Program. Because of their industry knowledge, and efforts. Physician interest and adoption of Skytrover continues to grow. As of February 28th, 704 Skytrover prescriptions have been written by 259 prescribers. 44% of prescribing physicians have written prescriptions for more than one of their patients. In November 2021, in Europe, we received a positive CHMP opinion for transcon growth hormone, for pediatric growth hormone deficiency, followed quickly by the European Commission approval in mid-January 2022. As a day's company, Europe is an important market to us, and the unmet medical need for pediatric growth hormone deficient patients is just as great. But because the market opportunity for growth hormone and timelines to secure reimbursement varies from country to country, we plan to advance to establish direct sales capabilities in some European countries and establish distribution partnership in others. In this way, we look forward over time to maximize value and intend to bring a broad portfolio of Transcon-based products to European physicians and patients. Moving to the adult growth hormone deficiency indication. We expect Transcon growth hormone to make a meaningful difference for adults suffering from adult growth hormone deficiencies. We expect by releasing unmodified somatopoeia, Transcon Gotamo may be able to address the many different aspects of the disease and restore overall endocrine health. In addition, during the second quarter of 2022, we plan to submit a protocol to the FDA internal syndromes. and comorbid disorder affecting development in females. We are pursuing this label expansion to help more patients and create a market-leading brand in growth hormone therapy. Turning now to transcomptate. We believe 2022 will be a very important year for patients living with hyperparathyroidism. who face significant challenges in both health and quality of life. Today, HP remains the last large classical hormone deficiency for which a hormone replacement therapy is not yet available. Conventional therapy with calcium supplement and activated vitamin D is aiming at maintaining serum calcium in the normal range with the hope of reducing short-term symptoms and is not able to address the underlying disease. In addition, these conventional therapies can lead to long-term complications. that include severe diseases such as chronic kidney diseases, renal and basal ganglia classification, cardiovascular complications, and bone damage. Numerous publications have reported that despite being unconventional therapies, patients continue to experience short-term symptoms, often resulting in hospital stays and emergency department visits. Finally, patients with HP report below normal quality of life at the same or worse level than many other chronic diseases, with significant impact on daily activities. With this in mind, we designed TransconPetate to restore physiological levels of parathyroid hormone, PTX. Later this month, we look forward to sharing top-line results from our Phase III pathway trial. As a reminder, this is a six-month randomized double-blind, placebo-controlled clinical trial in North America and Europe, investigating the safety, solubility of N-efficacy and transcom PTH in adults with HP. We believe that all chronic HP patients could benefit from a restoration of physiological levels of PTH. And we believe that Transcon PTH, if approved, could become an important treatment option for these patients. We are often asked, how does Transcon PTH differ from other PTH therapies that have been on the market? First, Transcon PTH allows the release of predictable levels of PTH in the physiological range across a 24-hour period. Second, we designed Transcon PTH to be a first-line hormone replacement therapy, potentially eliminating the requirement from conventional therapies by restoring calcium, hemostasis, and quality of life. Let me recap the Phase II data that gave us the initial insight in the potential for this important product candidate. In the open-label extension approach of the study, at month 6, 86% of the subjects had normal serum calcium, were off conventional therapy of activated vitamin D, and taking less than 600 milligrams per day of calcium. These are the same parameters being used as our primary endpoint in the Phase III trial. In addition, subjects reported normalized quality of life scores on all summary and subdomains. Importantly, subjects randomized to TransCon PTAs demonstrated a statistic improvement compared to placebo after four weeks in the blinded portion of the trial and continued normalization from week six to month six. We believe that these improvements in quality of life could be one of the main reasons why 57% out of 59 patients, continue to be part of the open-label extension study, even now, after two years. As you know, we remain excited by the data we have seen so far. And we think Transcon PTA could introduce a paradigm shift in how HP is treated. Among the phase three Assuming the Phase III results are positive, we plan to submit an NDA for Transcon PTAs to the FDA in the third quarter of 2022, followed by M&A submission to EMEA in the fourth quarter. In Japan, where the pathway to Japanese Phase III study of Transcon PTAs is underway, we expect top-line results in the third quarter. Because hypothyroidism can affect all ages, we also plan to initiate a study of transcompete AIDS in children with HHP during the fourth quarter of 2022. With an estimated more than 200,000 patients suffering from HHP in the US, Europe, and Japan alone, and the lack of option to treat the underlying disease. We believe Transcon PTA, if approved, could become our largest endocrine rare disease product. We think and believe Transcon PTA could potentially be the only product to fully address this plus 5 billion market opportunity. I would like to update you on Transcon CMP for a contemplation. Continuous exposure of CMP has shown to counteract the growth inhibition effect of FDR3 mutation associated with echocardioplasia and to stimulate growth. We are investigating Transcon-CMP's ability to provide prolonged exposure on CMP, allowing for penetration into the target growth plates. at predictable levels over time to rebalance the pathway that regulate growth. In the fourth quarter of 2022, we expect to share top-line data from the accomplished trial. Our Phase II randomized, double-blinded, placebo-controlled clinical trial of Transcon-CMP in North America, Europe, few other countries in New Zealand and Australia, aged from 2 to 10 with children with acondoplasia. In the accomplished trial, 42% of the shopping are in the age group from 2 to 5 years. We are really thrilled by the blinded safety data reported last December at our R&D update. And we are looking forward to share the top-line results in the fourth quarter of this year. Given the serious and irreversible early impact of this disease, we also plan during the second quarter of this year to file an IMD application or similar for accomplished infant trials in the patient age 0 to 2 years old. Stretching now to oncology, we believe our product candidates have the potential to transform cancer immunotherapy. Initial data from the Transcon TLR78 agonist first in human dose escalation trial has been promising, and we expect to see further validation of our technology and approaches in oncology later this year. For Transcon TLR78 agonist, Enrollment continues in Transcend IT101, a Phase 1-2 study of Transcon TLR78 agonists with or without checkpoint inhibitors in patients with advanced and metastatic solid tumors. We expect top-line dose escalation data for Transcon TLR78 agonist monotherapy and in combination therapy with checkpoint inhibitor in the third quarter of 2022. For Transcon IL-2 Beta Gamma, we expect top-line monotherapy data from the Phase I to, I believe, try in the fourth quarter of 2022. During the fourth quarter of 2022, we plan to submit an IND or similar for Phase II cohort expansion to investigate Transcom TLR78 agonist and Transcom IL-2 beta-garmin as a combination therapy. We took major steps in 2021 by progressing towards our vision 3x3. We believe we are moving towards becoming a viable, sustainable, and profitable biopharmaceutical company. We estimate that our first therapeutic area of endocrinology rare disease alone represents and combines 10 billion US global market opportunities. We also have a highly differentiated oncology pipeline and we plan to add a third therapeutic area. I look forward to updating you further as the year progresses. I will now turn the call over to Scott for a financial review before we open up for questions.