Ascendis Pharma A/S

Good day and thank you for standing by. Welcome to the Ascendus Pharma Third Quarter 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 1 1 on your telephone. You will then hear an automated message advising your hand is raised. We would also like to remind you that during this session, each person can ask only one question and one follow-up question. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Tim Lee, Senior Director, Investor Relations. Please go ahead.

Thank you, Operator. Thank you, everyone, for joining our third quarter 2022 financial results conference call. I'm Tim Lee, Senior Director of Investor Relations at Ascendance 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. Steena Singhal, Head of Clinical Development Oncology, Dr. Brigitte Volk, Senior Vice President, Head of Clinical Development and Medical Affairs, Endocrinology Rare Diseases, and Joe Kelly, Head of U.S. Commercial Endocrinology. 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 Skytropa for the U.S. market, the commercialization of Transcon HGH for the EU market, or our progress on our pipeline candidates and our expectations with respect to their continued progress, statements regarding the expected timing of approval and launch of Transcon PTH in the U.S. market next year, 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 Skytrova and our pipeline product candidate statements, regarding our planned regulatory filings, are expansion into new therapeutic areas and statements regarding the 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 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 statement section in today's press release in the risk factor 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 Skytropha 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. The European Commission has granted a marketing authorization for Lonefeg-Somatropin Ascentis Pharma, developed under the name Transcon HGH, as a once-weekly subcutaneous injection for the treatment of children and adolescents aged 3 to 18 with growth failure due to insufficient secretion of endogenous growth hormone. In general, we refer to this product as Transcon HGH, unless we're 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'll discuss our third quarter 2022 financial results and we'll provide further business updates. Following some prepared remarks, We will then open up the call for questions. I'll now turn the call over to Jan Mikkelsen, President and Chief Executive Officer.

Thanks, Tim, for this long introduction. Good afternoon and good evening, everyone. Again, an important quarter for Ascendix as we continue to achieve and approach new major milestones in our journey to fulfill them. Our vision, tree by tree, to become a sustainable, profitable, leading biopharma company. Earlier this week, we announced we had achieved another important milestone. As FDA has accepted for priority review our NDA for Transcon VTH for the treatment of adult patients with hypopara. FDA expects to complete the review of our NDA by April 30, 2023. We believe we will bring a totally new treatment paradigm to the Hypopera community. Today we are reporting Skytropha US revenue of 12.3 million euros this third quarter. Again, more than doubling our sales compared to last quarter. All patients continue in the Phase II accomplished trial for Transcon-CMP with no dropouts and the longest treatment duration now around two years. We are looking forward in the coming weeks to sharing top-line results, including OLE data in children aged 2 to 10 with achondroplasia. In oncology, we will have our first oral presentation at next week's Society of Immunotherapy in Cancer conference. We look forward to sharing our first in human safety and initial efficacy data supporting our recommended phase 2 dose for Transcon TLR78 agonist. Last quarter, I made the following statement. that we are on track to become cash flow positive, without the need for additional equity from investors. Given the successful launch of Skytober in the US, combined with the expected US launch of Transcon PTAs in the middle of next year, supported with our strong cash position of around 1 billion euro. After this quarter, my confidence that we will fulfill this belief has been reinforced. Okay, let me now share with you more details on our program. We designed Transcon Growth and More, now marketed as Skytrover in the US, to address the unmet medical need that results from children taking Data Growth and More. With a different set of products, we are building Skytober into the global market leading brand and at the same time expanding the overall value of the growth hormone market. For this quarter, we reported Skytober revenue of 12.3 million euros compared to 4.4 million euros in the second quarter. As we expect, the majority of patients will be on Skytropha treatment for at least three to five years. Revenue for each quarter becomes the new base for the next quarter. From that base, revenue continues to grow through the addition of new reimbursed patients. In Q4, we expect to grow the number of new reimbursed patients at a similar level to what we have saw in Q3, providing a strong base for revenue growth in 2023 and beyond. I believe with our improved commercial execution, we are achieving the goals we set out when we launched Skytropha in the US. By building on the product strength of Skytropha, and providing patients with a differentiated treatment. Over the coming quarters, we will continue to provide updates on all our programs that support our efforts to build Transcon Growth Hormone into a leading global brand in a growing growth hormone market. Let us turn to Transcon PTH. a product candidate we are dedicated to bring to patients as soon as possible. Earlier this week, we announced that FDA has accepted for priority review our NDA for transplant PTAs for treatment of adults with hyperparalysis. This is our second product candidate in a row that we are taking all the way from product design to successful regulatory filing. These patients faced an urgent need for treatment to effectively address their disease. Its complications, and importantly, help restore normal life for them. We hope to have a regulatory decision by April 13 of next year from FDA in the US. Our view of the importance of PTH replacement therapy was confirmed by the recent guidelines updates for the management of hypopara. The authors suggested consideration of PTH replacement therapy for HB patients insufficiently controlled due to any one of the following. Symptomatic hypocalcemia, hyperfoscemia, venal, insufficient, hypercalcivoid, or poor quality of life. They also observed that patients with poor compliance, more absorption, or who are intolerant of large doses of calcium and active vitamin D might also benefit from PTH therapy. With the potential to treat all HP patients regardless of disease background and growing evidence for long-term clinical trial data showing durable responses, we believe that transplant PTA could address this major unmet medical need. With the US regulatory timeline set, and review underway. We are focusing on preparation for an expected US approval and launch in Q2 next year. Expanding our global reach for Transcon PTAs. We are on track to submit our MAA in Europe and we remain on track to report top-line results from our Phase III partway Japan trial. Both events expected to happen this quarter. We are dedicated to further optimizing treatment options for patients. With up to three years of follow-up data from our clinical trials of Transcon PTH, we believe that HB patients on stable PTH doses a once-weekly PTA product could be a potential attractive treatment option. Our data demonstrates that each patient goes to multiple titrations and reads normalization of calcium hemostasis at different times. We believe once patients obtain their stable doses of daily Transcon PTAs, That is when they become optimal candidates for switching to a once-weekly PTH therapy with the same mode of action. Our once-weekly Transcon PTH product candidate, now in preclinical development, is based on the same Transcon technology and PTH parent drug as daily Transcon PTHs, enabling, we believe, predictable and safe switching of patients from daily to weekly Transcon PTH. Turning now to Transcon CMP. We are looking forward in the coming week to sharing top line results from the accomplished trial. Our phase two randomized double-blinded placebo-controlled clinical trial of Transcon CMP in children aged 2 to 10 with acondoplasia. The COMPIS trial was designed to enroll four dose cohort with up to 15 patient ease, randomized 3 to 1, active to placebo, in sequential cohort of 6 micrograms per kilo, 20 micrograms per kilo, 50 micrograms per kilo, and 100 micrograms per kilo per week, followed for one year on double-blinded basis. A total of 57 patients were enrolled in the four cohort, with four zero of the patients younger than five years old. All 57 patients enrolled completed the blinded portion with no dropouts. After one year of double blind treatment, patients transitioned from the dose cohort to an open-label extension, OLE, portion of the trial. As of today, all patients have been transitioned to the 100 micrograms per kilo per week dose level and all continue in the open label extension at that dose. We continue to see on a blinded basis the same well-tolerated safety profile we reported to you last December. with the longest treatment duration now around two years without any dose reduction and 100% patient retention. The primary endpoint of the ACOMTIS trial is analyzed high velocity after one year of treatment. The primary analysis is to compare mean analyzed high velocity for Transcon-CMP cohort to that for placebo-treated patients. We also plan to report the mean analyzed high-velocity data for the two patient groups, patients aged 2 to 5 and 5 to 10 years. In addition to the top-line randomized double-blinded data, we also plan to report preliminary data from the open-label extension portion of the study. These data will provide information on treatment impact when switching from placebo or lower dose up to 100 micrograms per kilo weekly dose of Transcon-CMP. I get a lot of questions about what my expectations are for this trial. First priority. First priority. Treatment needs to be safe and well tolerated. From the perspective of outcome, analyzed height velocity, or call it analyzed growth velocity, has been validated as the regulatory primary endpoint. Just as with height velocity in other growth disorder trials, this endpoint in acroendoplasia is dependent on multiple demographic factors. In particular, the age of the patient is a major factor determining the outcome. For the only approved treatment in the US for acondyloplasia, the analyzed high velocity for patients aged 5 to 14 was around 5.4 cm per year. with a greater treatment effect in analyzed height velocity for the age group 8 to 11 compared to the age group 5 to 8. I estimate the benchmark for analyzed height velocity for the age group 5 to 10 in the accomplished trial will be slightly lower than the 5.4 centimeter per year. as the accomplished trials have fewer patients in the faster-growing age group of 8 to 11 compared to the age group of 5 to 8. To further evaluate Transcon-CMP at 100 micrograms per kilo per weekly dose, We have submitted a protocol to FDA to initiate a global randomized double-blinded placebo-controlled phase IIb trial in children with alcoholism from 2 to 11 years of age. This trial is expected to enroll about 80 patients and measure, analyze growth velocity after one year of treatment at the primary endpoint. Perhaps more important, we believe this trial will enroll sufficient patients to analyze additional secondary endpoints, which may help to explain why we see 100% patient retention in our trial. We expect to complete enrollment early next year of this trial. In summary, we remain on track with our vision 3x3 goal to obtain approval for three endocrinology rare disease products by 2025. Turning now to oncology. With our first two immunotherapy programs, we are levering both the Transcon systemic technology for Transcon IL-2 beta gamma, and for first time in humans, the Transcon hydrogel technology for Transcon TLR-7-8 agonist. TRANCON TLR78 agonist is designed to kickstart the immune system inside the tumor and using our intertumor hydrogel technology to provide sustained release of the TLR78 agonist over weeks, thereby activating the immune system within the tumor microenvironment without systemic toxicity. We recently completed dose escalation and declared the recommended Phase 2 dose for our Transcon TLR78 agonist candidate. With a favorable safety profile and early signs of clinical activity observed as monotherapy or in combination with a checkpoint inhibitor, we are pleased that our abstract for top-line dose escalation data was selected for an oral presentation at CITSI, the annual meeting of the Society for Immunotherapy in Cancer being held in Boston next week. Our second oncology product candidate, Transcon IL-2 Beta-Gamma, is designed to broadly increase systemic stimulation of the body's immune system, and we believe it has the potential to become a new backbone for cancer immunotherapy. Transcon IL-2 beta gamma continues to be well-tolerated as monotherapy or in combination therapy, and we're seeing promising pharmacodynamic responses and we're continuing dose escalation. We plan to share monotherapy top-line results later this quarter. As you can hear, there are so many great milestones we have achieved, but also so many, many more in the near term. With a cash position of €935 million, Ascentis is on track to achieve our vision 3x3 and I remain confident in our ability to drive continual progress. I will now turn the call over to Scott for additional details and a financial review before we open up for questions.