Ascendis Pharma A/S

Good day and thank you for standing by. Welcome to the Ascendance Pharma second quarter 2022 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 11 on your telephone. You will then hear an automated message advising that your hand is raised. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker for today, Mr. Tim Lee, Senior Director of Investor Relations for Ascendis Pharma. Please go ahead.

Thank you, Operator, and thank you, everyone, for joining our second quarter 2022 Financial Results Conference call today. I'm Tim Lee, Senior Director of Investor Relations of Ascendis Pharma. Joining me on the call today is Jen Mickelson, President and Chief Executive Officer of Scott Smith, Senior Vice President and Chief Financial Officer. Dr. Dana Fizzuti, Head of Development Operations and Chief Medical Officer. Dr. Steena Singhal, Head of Clinical Development Oncology. And Joe Kelly, Head of U.S. Commercial Endocrinology. Before we begin, I would like to remind you that this conference call will include four looking statements that are intended to be covered under the safe hardware 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 Skycopo for the U.S. market, the commercialization of Transcontinental HGH for the EU market, our progress in 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 Skytropha and our product pipeline candidates, statements regarding our planned regulatory filings, our expansion into the 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 for those in the four linking statements and we may not be able to achieve our goals, carry out our plans or intentions or 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. Expect as required by law. For additional information concerning the factors that could 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 Skytropa for the treatment of pediatric patients one year or older weighing 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 marking authorization for Lonepeg Somatropin Ascendant Pharma, developed under the name Transcon HGH, is a once-weekly subcutaneous injection for the treatment of children and adolescents aged 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 second quarter 2022 financial results and will provide further business updates. For honest and prepared remarks, we'll then open the call up for questions. I will now turn the call over to Yen Mickelson, President, Chief Executive Officer.

Thanks, Tim, and good evening, everyone here from Copenhagen. With our recent clinical and regulatory progress for Transcon PTH and the commercial progress for Skynetropa, we continue to work toward fulfilling our vision tree by tree to become a sustainable, profitable, leading biopharma company. For Transcon PTAs, we have reported positive phase three data, which met the compulsive primary endpoint and all key secondary endpoint, highlighting its potential to address a major unmet medical need for adult patients with hyperparathyroidism. After a positive and constructive pre-NDA meeting with FDA, we are on track to submit regulatory findings in the US in the coming week and in EU during Q4. This year, we continue to advance our goal of making Skytofa the leading product in a growing growth hormone market. in our planning to launch SCARTOFA in Europe next year. We have now achieved successful phase 3 results for two independent product candidates in a row and continue to see highly consistent clinical trial results across multiple geographies and populations. We believe that we are well positioned to drive sustainable long-term growth with our three additional independent clinical product candidates in rare disease endocrinology and oncology. That applies the same algorithm for innovation that we use for scitopha or transcomptase. We believe that we are on track to become cash flow positive. Given our strong cash position, of around 1 billion euro, combined with the expected revenue from Skartrofe in the U.S., combined with the expected U.S. launch of Transcon PTAs in the middle of next year. Now, let me update you on each of our programs. For Transcon growth and more, market at Skartrofe in the U.S. Our commercial strategy is to build Skytober into the leading growth hormone product in value, while growing the overall value of the growth hormone market. Our once-weekly Skytober is differentiated from other once-weekly growth hormone products in multiple ways that reinforce its value. Skytober is the only once-weekly product to deliver unmodified somatopine, thereby maintaining the same mode of action as denicotinol. In addition, it's the only product with room temperature storage, no preservatives, and an empty old cartridge which provides clear, visible evidence to patients and caregivers that injection has been delivered. I'm also proud to share with you that the Skytropha Autoinjector was awarded PharmaPax 2022 Patient-Centric Design Award. This prestigious award recognized pioneering drug-delivered solutions that have significantly contributed to improved design innovation, patient experience, and ease of use. This changed the U.S. commercial leadership in May. And the new leadership immediately implemented improved commercial tactics for SkyFOFA. One of the goals behind these changes was to increase conversion of prescription to paid reimbursed therapy. We have already seen the benefit of this effort. With a more than doubling sequential resulting in a reported revenue of 4.4 million euros in Q2 compared to 1.9 million euro in Q1. Nearly half of Q2 revenue were generated in the month of June alone. We also seen an increase in the number of Skytrover prescriptions written for new patients. With a total number more than 1,700 at the end of Q2. A typical prescription has a duration for one year. This is an increase of 75% compared to the end of Q1. With this improved commercial tactics, we believe we are on track to achieve current 2022 full-year a census-compiled, sell-side-analyst-consensus-Skytofer revenue estimate of around 25 million euros. We continue our efforts to build Transcon-Glutamone to a leading global product with a global phase 3 adult Glutamone deficiency trial. pediatric growth hormone deficiency trial, and a planned Turner syndrome trial. Let us now turn to Transcon PTH, potentially our most valued product candidate in endocrinology rare disease pipeline. We designed Transcon PTH to release PTH and physiological levels over 20 hours to deliver the missing endogenous PTH. We believe that Transcon PTAs has the potential, if approved, to become the first hormone replacement therapy to address the underlying cause of this disease. For this reason, we believe that Transcon PTAs is the only product candidate that can properly and completely address this more than 5 billion market opportunity. The results from our Phase 3 trials, which met the composite primary endpoint and all key secondary endpoints, along with our Phase 2 trials, support our belief in this potential. Even more promising, 57 out of 59 patients continue in the open-label portion of the Phase 2 trial during two years of treatment. And 78 out of 79 patients continue in the open-label portion of the phase three trial. All that reinforce our view that this product candidate is having an ongoing impact on this patient's life. These positive results were consistent across Transcon PTH-treated adult patients, independent of their disease background or conventional therapy dose at baseline. which gives me comfort that basically all adult hyperparaparism patients have the potential to benefit from treatment with transcomptetase. With this long-term and pivotal data in hand, and our planned NDNA submission in the coming weeks, we are focusing on preparation for the expected U.S. approval and longs in mid-2021. We have identified three segments within the estimated 70,000 to 90,000 patients with chronic HP in the U.S. The first segment consists of adult patients in the U.S., previously or currently treated with short-acting PTH preparation. All true, most of them no longer have access to this treatment because of the recall of NatPara in the U.S. This patient group, we believe, can be the early adapters of Transcode PTAs, as they have previous experience with PTAs treatment. The second and last segment consists of chronic adult HP patients. currently on conventional therapy with active vitamin D and calcium supplement, who remain PTH treatment aid. In this segment, we will focus on building awareness for patient, providers, and healthcare system to understand the clinical value of transcom PTH treatment. The third segment consists of newly diagnosed adult patient with chronic HB. Patients in this group often develop chronic HB as a result of next surgery on therapies that result in removal or damage to the parathyroid glands. In addition, we plan to explore the potential benefit of Transcon PTA more broadly in post-surgical settings and pediatric patients in future clinical studies. Expanding global reach for Transcon PTA. We expect a potential approval in EU in Q1 2024, followed by a long shortly thereafter. For Japan, we plan to report top-line results for our Phase 3 partway Japanese trial in the fourth quarter of this year. Switching now to Transcon CLP. The countries trial, our Phase 2, randomized, double-blinded, placebo-controlled clinical trial of Transcon-CMP in children with echocardiopathy from the age of 2 up to age of 10 continuous. We are pleased to report that we continue to see a well-tolerated safety profile, and all patients continue in their trials with the longest treatment duration now about two years without any dose reduction or discontinuation. All patients in the open labelling extension are now on 100 micrograms per kilo per week at dose. We look forward to sharing the top-line results from the double-blinded placebo-controlled part of the ACOMDIS trial and the open labelling extension results during the fourth quarter of this year. We are planning to submit a new protocol to our in the U.S. and submit CTAs in countries in the EU in Q4 this year in order to initiate a new global randomized double-blind placebo-controlled phase two trial in a contemplative patient down to the age of two. The trial is expected to enroll around 80 patients and measure analyzed growth velocity at the primary endpoint. We expect to have the top line results at this clinical trial in 2024. With this, we believe that we remain on track to our overall vision, three by three, goals of attaining approval for three endocrinology rare disease product by 2025. Turning now to oncology. Based on our recent progress, I am more and more convinced that we can make a paradigm shift in the treatment of cancer because of our unique Transcon technologies. The Transcon TLR78 agonist is designed to kickstart the immune system inside the tumor, where our hydrodialysis technology provides sustained release of the TLR78 agonist, thereby activating the immune system without systemic Enrollment continues in our phase one to trial of transplant TLR agonist therapy alone in combination with a checkpoint inhibitor in patient with solid tumor who has failed prior lines of therapy. The trial continues to show transplant TLR agonist is well tolerated as a monotherapy or in combination with a checkpoint inhibitor. consistent with low systemic exposure of TLR78 agonist and demonstrating preliminary evidence of anti-tumor activity as monotherapy or in combination with a checkpoint inhibitor. Our Transcon IL-2 beta-gangloprotein candidate is designed to broadly increase systemic stimulation of the body's only anti-cancer system and to become a new backbone for cancer immunotherapy. The phase one to dose escalation and dose expansion trial continues to evaluate this product candidate alone or in combination with a checkpoint inhibitor or chemotherapy in patients with solid tumor who have failed prior line of therapy. During the second quarter, we dose our first patient in the combination transcon IL-2 beta gamma and checkpoint inhibitor. The phase 1-2 trial continues to show transcon IL-2 beta-gamma is well tolerated as mono-3 or in combination therapy. Today, we have seen dose-dependent increase in absolute lymphocyte count, along with increases in pseudotoxic subset cells of CD8-positive cells and NK cells, without an increase in in eosinophils, indicated the intended design bias towards beta gamma activity. There had been no dose limit toxicity reported to date, and we continue with dose escalation. I will now turn the call over to Scott for additional details and a financial review before we open for questions.