Ascendis Pharma A/S

Hello, and welcome to Ascender's Farmer Q2 2023 earnings conference call. At this time, all participants are in the listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask the question during this session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, press star 11 again. I would now like to hand the conference over to Tim Lee, Senior Director, Investor Relations, Ascendus Pharma, AS, so you may begin.

Thank you, operator, and thank you, everyone, for joining our second quarter 2023 financial results conference call. 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, Executive Vice President and Chief Financial Officer, and Dr. Stina Singel, Executive Vice President of Head of Clinical Development Oncology. Before we begin, I'd 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 Skytropha for the U.S. market, our revenue projections for Skytropha, the commercialization of Transcon HGH for the EU market and our planned launch of Skytropha in Germany, statements regarding our NDA for Transcon PTH and the expected timing of the potential approval and launch of Transcon PTH in the US market, statements regarding the expected timing of the potential approval and launch of Transcon PTH in Europe, statements regarding the potential approval of Transcon CMP, our expectations regarding our new Transcon technology, and 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 our pipeline product candidates, statements regarding our ongoing and planned regulatory filings, and our expectations regarding the timing and the results of regulatory decisions, our expansion into new therapeutic areas, and statements regarding our progress towards vision 3x3 and our ability to create a sustainable, profitable, and leading global pharma company. These statements are based on information that is available to us today. Actual results and events could differ materially from those in our forward-looking statements, and we may not be able to achieve our goals, carry out our plans, our intentions, our 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 And the risk factor section of our most recent annual report on Form 20F filed February 16, 2023. 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 and older weighing at least 11.5 kilograms and having growth failure due to inadequate secretion of endogenous growth hormone. In addition, the European Commission has granted a marketing authorization for Skytropha to Ascendis Pharma, developed under the name Transcon HGH, as a once-weekly sub-case 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 Growth Hormone unless referring to the product in the context of particular jurisdictions 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 in the conference call regarding our product candidates shall be viewed as promotional. On the call today, we'll discuss our second quarter 2023 financial results and we'll provide further business updates following some prepared remarks We'll then open up the call for questions. I'll now turn the call over to Jens Mikkelsen, President and Chief Executive Officer. Jens?

Thanks, Tim. Good afternoon, everyone. In 2019, at the J.P. Morgan Conference, we announced our vision three by three for building a leading sustainable global biopharma company by 2025. Today, I'm pleased to share with you an update on how close we are to achieving our vision. As outlined in our vision 3x3, using our Transcon technology platform and our algorithm for product innovation, we are on the pathway to achieve the regulatory approval of three independent endocrinology rare disease products, Transcon Grotamo, Transcon PTH, and Transcon CMB by 2025. In addition, we are building global commercialization capabilities to bring this growing portfolio of highly differentiated products to patients. In the US, for the second quarter, we reported Skytrover's revenue of €36 million. Skytrover achieved growth hormone market value leadership in the U.S. in the second quarter, with a penetration of less than 10% of treated U.S. pediatric growth hormone deficiency patients, which represent about half of the growth hormone market in the U.S. today. For the full year of 2023, we now expect Skytropha U.S. revenues to be €165 to €170 million. We believe three factors continue to drive demand. First, a growing number of physicians have patients with over a year of experience on Skytover, and these physicians have observed the long-term benefit for both treatment-naive and switch patients. The consolidation of the daily growth hormone market continues, and the recent approvals of two other long-acting growth hormone products could accelerate this shift to long-acting. Third, Ascendis has become a trusted partner within the endocrinology community. As we continue to invest in our products, in science, and in our support for patients and healthcare, and provide them with a reliable supply chain. In our global commercial reach, we are ready to launch SCARTOVA this month in Germany. Our medical affairs and commercial teams are in place and have been active in engaging endocrinologists across the country. We recently received FDA approval at Launce for a high-capacity drug-softened manufacturing site, for which we expect EU approval in the first half next year. This added drug-softened manufacturing capacity supports our goal to commercialize in new markets and additional indications. and to achieve our goal of global market leadership and value in a growing global growth hormone market. During the fourth quarter, we expect to see a top-line result for our global phase 3 foresight trial of transgrown growth hormone in adult growth hormone deficiency. We believe adult growth hormone deficiency is an under-penetrated indication. The recent study showed that less than 4% of adult patients suspected of having growth hormone deficiency are treated with growth hormone. Moving to Transcon PTH for adult hyperparathyroidism. In June, we requested a type A meeting with FDA and submitted an updated control strategy. The Type A meeting was held with FDA in late August based on the agency's availability. Following a constructive Type A meeting, we submitted additional information to FDA supporting the updated control strategy. I believe the materials submitted to FDA combined with the Type A meeting discussion will position us to resubmit the NDA for transcort PTH for adults with hyperparathyroidism in October 2023. If our NDA is accepted, which we expect within 30 days following resubmission, FDA will notify us where the resubmission is class 1 or class 2 and provide a new PDUFA date, which we estimate could be in December this year or April 2024. It is important to note that we will not know the new PDUFA date until our Resubmission is accepted and its classification is communicated to us. Besides this information, we will not comment further on the Resubmission procedure while we are having ongoing communication with FDA. In the European Union, We received our day 180 assessment report with feedback on our MAA for Transcon PTAs and have submitted our response to the list of outstanding issues. We remain on track for a European Commission decision during the fourth quarter. And if approved, we plan to launch Transcon PTAs in Germany in early 2024. Finally, today we released new positive data supporting the potential beneficial effect of Transcon PTH on kidney. Over the course of one year, patients in our phase 3 trial demonstrated profound increases in EGFR, a key marker of kidney function, with increases of around plus 9 milliliter per minute across all patients. Importantly, in the subset of patients with EGFR less than 60 at baseline, the threshold for kidney dysfunction, Transcon PTAs demonstrated increases of 11 to 12 milliliters per minute. Around half of the pathway for patients with an EGFR of less than 60 after Transcon-P treatment for one year, experience at EGFR improving to about 60, meaning they went for having a diagnosis of renal impairment to be within the normal range of kidney function. For patients treated with Transcon-PT8, sustained improvement in EGFR, of this magnitude may reduce risk of progressing to chronic or late-stage kidney diseases. This is a major comorbidity in patients with hyperparathyroidism and a major contributor to medical costs. We plan to present detailed results at our upcoming medical conferences. The U.S. Expanded Assess Program and German Compassion Youth Program for Transgender and PTA continues to be old for enrollment of patients. And we expect to imitate comparable programs in additional countries. In the ongoing extension portion of our clinical trial, 145 out of the initial 154 patients from the original clinical trials continued treatment with Transcom PTH for over three years. We continue to prepare for the expected launch in the U.S. and Europe. We are confident that Transcon PTA can, if approved, become an important new treatment option for adult patients living with these serious diseases. Switching now to Transcon CMP. Following our end-of-phase two meetings with U.S. and EU regulatory agencies, we have an agreed pathway to achieve regulatory approvals for Transcon-CMP. First, FDA and EU regulatory agencies confirmed that absolute analyzed growth velocity is acceptable as the primary input for Roswell Pivotal Phase III approach trial. Second, these regulatory agencies agreed to our dose selection of 100 micrograms per kilo per week dose for approach. Third, based on this discussion, we expect that an indication for treatment of achondroplasia will be supported by evaluating the beneficial impact on Transcon-CMP, on comorbidities, and other important aspects of achondroplasia, in addition to height. Fourth, our PIVOLOL phase 3 trial approach is now fully enrolled with top-line data expected in the second half of 2024. We believe that achondroplasia is a disease of both skeletal growth and muscle disorder. Based on the rapid functional improvement observed in our ongoing Phase II accomplished trial and based on literature review, there may be a primary muscular component to achondroplasia phenotype. besides the well-described effect on skeletal growth. We believe it's essential to have a continuous exposure to CMP to optimally improve muscle strength and endurance. In our PUPIL trial, we will explore endpoint to measure how CMP might moderate the muscular weakness. In addition, This also means that there could be a treatment option for adults living with achondroplasia. Our research in this area continues, and we expect to share more later this year, along with new data from a campus where all the initial 57 patients continue on treatment with Transcon-CMP for over three years. Turning to oncology, we today announced that we had completed dose escalation for Transcon IL-2-Basagamma in combination with PEMBO and declared recommended phase 2 dose at 120 micrograms per kilo every three weeks. No dose-limiting toxicity, vascular leak syndrome, or grade 3 or 4 cytokine release syndrome were observed at any dose level evaluated. Finally, I am excited to share with you some new developments expected to drive Ascendi's sustained growth. We have developed a new transcontinental carrier platform, which integrates our reversible linkers and complements our two established carrier technologies, the soluble and hydrogel platforms. Among the many applications, we believe these technologies support high-volume, low-cost manufacturing enabling products for new therapeutic errors. We have established proof of principle for once-monthly dosing of the GPL1 analog semaglutide, and on our website, you can see our preclinical data. In summary, Ascendix remains focused on building and maintaining a sustainable, profitable, leading biopharma company. With all programs making significant progress, we are nearing completion of our vision 3x3 and have already begun the foundation for the next stage of Ascendance. I will now turn the call over to Scott for a financial review before we open up for questions.