Ascendis Pharma A/S

Good day and thank you for standing by. Welcome to the first quarter 2022 Ascendus 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 the session, you will need to press star and then one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star and then zero. I would now like to hand the conference over to your speaker today, Tim Lee, Senior Director, Investor Relations. Please go ahead.

Tim Lee Thank you, operator. Thank you, everyone, for joining our first quarter 2022 Financial Results Conference call today. I'm Tim Lee, Senior Director, Investor Relations of Ascendus Pharma. Joining me on the call today is Jen Mickelson, President and Chief Executive Officer, Scott Smith, Senior Vice President and Chief Financial Officer, Dr. Dana Pizzuti, Head of Development Operations and Chief Medical Officer, Dr. Yuha Poonanen, 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 statements may include but are not limited to our U.S. commercialization and continued development of Skytrofa for the U.S. market, the commercialization of Transcon HGH for the EU 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, including the timing of clinical results, statements regarding the U.S. market approval of Skytrofa, and our pipeline product candidates, statements regarding our planned regulatory filings, our expansion to new therapeutic areas, and statements regarding our ability to create a sustainable, leading global biopharma company. 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 be able to 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 cause actual results to differ materially, please see our forward-looking statement section in today's press release and the risk factors section of our most recent annual report on Form 20F filed with the SEC on March 2, 2022. Transcon Human Growth Hormone, or Transcon HGH, is approved by the FDA in the U.S. under the brand name Skycropa 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 Lone Rumpet Xanthotropin Ascendis Pharma, developed under the name Transcon HGH, as a once-weekly subcutaneous injection for the treatment of children and adolescents age 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. Otherwise, please note that our product candidates are investigational 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 our first quarter 2022 financial results and will provide further business updates. Following some prepared remarks, we will then open up the call for questions. I will now turn the call over to Jens Nicholson, President and Chief Executive Officer.

Jens Nicholson, President and Chief Executive Officer, Jens Nicholson, President and Chief Executive Officer, Thanks, Tim, and good afternoon. 2021 was an extraordinary year for Ascendis. As we became a fully integrated commercial states biopharma company, the balance of in the U.S. and the expansion of our clinical pipeline to five independent programs in endocrinology, rare disease, and oncology. These successes confirm that we have the right strategy, the people and capabilities in place to allow us to achieve our vision tree by tree. and to build a sustainable, profitable, leading global biopharma company. In 2022, we have already achieved an important milestone. In March, we reported results for the Transcon PTH phase 3 program, and our pathway trial met the primary and all key secondary endpoints. Transcon-PTH is a product candidate, addressing a major unmet medical need for adults with chronic hypoparathyroidism patients. A large rare disease population with around 200,000 patients in North America, Europe, and Japan alone. It is rare for a biotech company to have two potential blockbuster product candidates in a row achieving their target product profile and successfully meet their phase three trial objectives. What has put Ascendis in this unique position? First, our Transcon technology platform and our approach to product innovation, the uniqueness of the Transcon technology platform, combining the benefits of two independent technology platforms, the classical product technology and a predictable sustained release technology. The Transcon technology platform can be applied broadly to multiple dog types, We believe this, combined with our validated approach to product innovation, enables us to achieve a higher rate of success compared to traditional drug development. Second, our commitment to patients and their science. Our commitment to patients and science has guided our product development strategies. We seek to design optimal clinical programs to bring differentiated product candidates to patients as quickly as possible with robust clinical data. Third, and in this time, perhaps extremely important, we have a strong balance sheet to support long-term strategic executions. we have the capital necessary to deliver on both short and long-term goals. During the first quarter, we further strengthened our balance sheet to a convertible notes offering. As a result, with the cash on hand today, we believe we are well positioned to deliver on our vision 3x3 strategy, independent of further financing. What makes me so optimistic for the future, so optimistic for the patient, so optimistic for Ascentis is that all our five independent clinical programs are based on the Transcon technology platform and developed using the same algorithm for product innovation. And we will navigate the regulatory pathway with the same experienced global Ascendis team that brought Transcon Growth Hormone to approval in the US and Europe. We believe we have demonstrated that we have the fundamentals for creating a continuous stream of product candidate with the potential to address major unmet medical needs with greater success than traditional drug development. In short, we believe Ascendis has the right approach a growing portfolio of product candidates, the right people and capabilities, and the necessary funding to deliver on our goal to create a sustainable, leading global biopharma company. Throughout the rest of the year, we look forward to sharing clinical data from across our pipeline, including our third endocrinology rare disease product candidate, Transcon-CMP in Fort Worth and from our oncology programs, which have multiple important milestones this year. For Transcon-Glutamone, which is now approved in both the U.S. and Europe, we continue to build awareness and increase adoption and covers in the U.S., where it's marketed under the brand name Skytofa. We believe that SkyTrofa is a unique, important treatment option for patients. And we are determined to build it into a leading global brand. As we work to shift the daily treatment paradigm for physicians and payers, I'm pleased to share that brand penetration continues to grow with increased prescriptions, treated patients, and covered lives. As part of our commitment to make Transcon Growth Hormone the leading treatment option in the global growth hormone market, we continue to recruit patients for our global phase three foresight trial of Transcon Growth Hormone in adults with growth hormone deficiency. As a result, of the ongoing war in Ukraine. We do not expect any patient in certain Eastern European countries to be part of the Foresight Trial. And we have modified our recruitment efforts to focus on our countries to compensate. As a result, we are now targeting completion of enrollment of the Foresight Trial during the fourth quarter of this year. In addition, to support further label expansion for trans-con growth hormone. We are planning a protocol submission in the second quarter to FDA for Turner syndrome. Turning now to trans-con PTHs. We believe that the best way to treat a hormone deficiency is to replace the missing endogenous PTH hormone at physiological levels over 24 hours. For this unmet need, we designed Transcon PTA to become, if approved, the first complete PTH hormone replacement therapy, with addressing the underlying cause of this disease. The positive phase III pathway trial results from the composite primary endpoint and all key secondary endpoint confirm our belief in this potential. As a reminder, the phase III results at week 26, the data showed that 95% of transcomptate treated patients, that is, 57 out of 60 patients were able to eliminate, eliminate conventional treatment with therapeutic doses of calcium supplement and active vitamin D. In addition, for the key secondary endpoint, two separate quality of life instruments show Transcon PTH treated patients reported significant decrease in disease symptoms and significant improvement in their physical function. Our Phase II and Phase III trials are the first clinical trials ever to show statistic improvement in quality of life measurement and demonstrate consistent results across both studies. I believe these improvements, specific renormalization of quality of life measurement are why, after more than two years, 57 out of 59 patients in our Phase II trial and all 79 patients who completed the Phase III trial are continued treatment in these studies. These results from our trials are promising outcomes for adults suffering from chronic ASPs. who often experience multi-organ comorbidities and a diminished quality of life. We are doing the work required to build this new market and treatment paradigm because these patients deserve a better life. Understanding the urgent need, we are working to bring Transcom PTAs through the regulatory process in the US and Europe as quickly as possible. The robust data sets from our Phase 2 and Phase 3 studies will be the foundation of our planned U.S. and European regulatory findings, which remain on track with a U.S. NDA-finding plan for Q3 and a European MAA-finding plan for Q4. In Japan, we recently completed enrollment in our pathway Japan Phase 3 trial. and we plan to report top-line results later this year, which demonstrates Ascendi's global development capabilities. If approved, we believe Transcon PTH has the potential to become our largest endocrinology rare disease product, and the only PTH replacement therapy available in an estimated more than 5 billion plus market opportunities. Let me switch now to Transcon-CMP for a contemplation. We designed Transcon-CMP to provide sustained release of an effective level of CMP over the course of a week, while avoiding a high CMAX which may be the driver of cardiovascular complications. Last December, We completed enrollment and accomplished our Phase 2 randomized double-blinded placebo-controlled clinical trials of Transcon-CMP in children with acondyloplasia from the age of 2 up to 10. We look forward to sharing the top-line results for this Phase 2 study during the fourth quarter of this year. Moving to oncology, an era where unmet need remains high. In oncology, we are applying the same algorithm we have used in endocrinology rare diseases to bring forward product candidates that we believe will address major unmet medical needs with higher success compared to traditional drug development by building on well-understood biological pathways. We believe that transplant technology can address some of the challenges that have limited these immunotherapies and address additional aspect of the immunity cycle to induce the patient's own immune system to potentially eliminate the tumor. To transform this treatment paradigm in oncology, we are using Transcon intratumor and systemic technology to enhance intratumor effects. by providing sustained modulation of tumor microenvironments and activating of pseudotoxics in immune cells. Transcon TLR78 Agonist is using the Transcon intertumor technology platform and is designed to kickstart the immune system inside the tumor. Transcon IL-2 Beta Gamma is using the Transcon systemic technology platform and is designed to increase the systemic stimulation of the body's own cancer immune system. We believe Transcon IL-2 Beta Gamma development program may yield advances over all current treatment options. We are beginning to see promising results and we will provide additional data by the end of the year. The results we plan to present later this year will include additional clinical data from our TLR7-8 agonist program. At the end of last year, we reported early signs of clinical efficacy and a well-tolerated safety profile. Enrollment continues in our Phase 1-2 study of Transcon TLR788 agonist monotherapy and in combination with checkpoint inhibitor in patients with advanced or metastatic solid tumor. Later this year, we expect to share both top-line monotherapy and combo therapy dose escalation data from this trial. For Transcon IL-2 Beta Gamma, we have already moved into our third monotherapy cohort in our Phase I-II, I believe, trial, with dosing at 80 micrograms per kilo, with the expected strong safety profile and effect just as we designed this molecule. We are using the Transcon technology to release a permanent high-potent beta-gamma-bias IL-2 molecule. Through the Transcon technology, we are flattening the PK profile and expanding the therapeutic window by avoiding the hyzimax that is known to drive toxicity. During this summer, we look forward to share initial data related to transcon IL-2 beta gamma activation of the vector immune cells. We also expect top-line monotherapy data by the end of 2022. Later this quarter, we are targeting the first patient dose in a combination therapy portion of phase 1 to IL-2 beta, I believe, trials. Transcon IL-2 beta gamma and Transcon TLR-7-8 agonist act on different parts of the immune system. And we are developing the programs in parallel, as we believe they could be working together in synergy to become a new backbone in therapy, in immunotherapy, independent of checkpoint inhibitors. We expect to initiate clinical trials exploring this potential clinical synergy together later this year. Going beyond endocrinology and oncology, we are finalizing the selection of our third therapeutic area. And I'm looking forward to sharing more information of this with you in the end of this year. It's the best time for incentives, but we never forget why we're here. to make a meaningful difference in the life of patients. Our corporate strategy has been clearly defined in our vision 3x3, and we continue to achieve consistently impactful results as we're walking across the portfolio. The values that drive our organization, patient, science, and passion, combined with our strong financial position and expanding in-house capabilities, position us to advance the regulatory, clinical, and commercial milestones that will contribute to our long-term sustainability and profitability. I firmly believe we have the right team, culture, and capability in place to execute. I will now turn the call over to Scott for additional details and financial review before we open for questions.