Ascendis Pharma A/S

Hello, and welcome to the Ascendus Pharma third quarter 2023 earnings conference call and webcast. Following the prepared remarks, there will be a question and answer period. Instructions will be given at that time. I would now like to hand the conference over to Tim Lee, Senior Director, Investor Relations, Ascendus Pharma. Senator, you may begin.

Thank you, Operator, and thank you, everyone, for joining our third quarter 2023 financial results conference call. I'm Tim Lee, Senior Director of Investor Relations at 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. Sina Singhal, Executive Vice President and 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 statements regarding our commercialization and continued development of Skytrofa for the U.S. and European markets, as well as our expectations for 2023 Skytrofa revenue, the expected timing of the approval and launch of Transcon PTH in the U.S. and the EU, our pipeline candidates and our expectations with respect to their continued progress and potential commercialization, our strategic plans, our goals regarding our clinical pipeline, including the timing of clinical results, our ongoing and planned regulatory filings, our expectations regarding the timing and the results of regulatory decisions, our expansion into new therapeutic areas, our progress toward Vision 3x3, and our ability to become cash flow positive and 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 can differ materially from those in our forward-looking statements, and you should not place undue reliance on these statements. We assume no obligation to update these statements as circumstances change, except as required by law. For additional information concerning the factors that can cause actual results to differ materially, please see our forward-looking statement section in today's Today's press release in the risk factors section of our most recent annual report on Form 20F filed February 16, 2023. Pranscon Growth Hormone, or Pranscon HGH, is approved in the U.S. by FDA, and the EU has received MAA authorization from the European Commission for the treatment of pediatric growth hormone deficiency. 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 during the conference call regarding our product candidates shall be viewed as promotional. On the call today, we'll discuss our third quarter 2023 financial results and we'll provide further business updates. Follow us in prepared remarks. We'll then open up the call for questions. And with that, let me hand it over again.

Thanks, Tim. Good afternoon, everyone. Our dedication to the values of patients' science and passion remains the foundation for incentives to create long-term value for all stakeholders. In the U.S., we achieved market value leadership for SkyTofa within two years by sticking to our belief that a premium product deserves a premium price. Following the same strategy in Germany, we launched SCOT-HOFA in September and also expect to also launch Transcom PTAs in January 2024, if approved by the European Commission in November. In select other European countries, we will use the same direct sales model to launch our portfolio as we have in the US and Germany. We call this EU Direct. In other markets, we will commercialize our portfolio to sales and distribution partners who are local experts in their diseases. We refer to this as international indirect markets. In Japan, we intend to partner our endocrinology rare disease products. We believe we have the organization and the manufacturing capacity to support expected launches of three independent endocrinology rare disease products by 2025. Driving further growth, we aim to continue to work to create highly differentiated transplant product candidates. expanding into additional endocrinology rare disease indication. Last quarter, we announced the expansion of our Transcon platform, a new type of carrier platform, specific designed to support new product opportunities in diseases with large patient population. I look forward to share more information with you about this in the near future. Let me provide more details on each of our programs. For Transcom Go to Moon, commercialized at Skatoka, we reported strong revenue growth, finished the third quarter with 47 million euros, including initial revenue from Germany. We now expect full-year 2023 Skytofa revenue to be between 170 and 175 million euros. To drive differentiation and market leadership, we continue to build on the science and data behind Skytofa. We recently announced results from our long-term extension trial showing that the majority of patients treated with transplant dopamine met or exceeded average parental height SDS at the time of their treatment completion or last visit. The data also demonstrated the long-term safety of SCARTOSA in patients treated after six years. In adult growth hormone deficiencies, we expect to see a top-line result during the fourth quarter from our global phase 3 foresight trial. Today, we estimate less than 4% of adult patients suspected of having growth hormone deficiency are treated with growth hormone, making this an opportunity to both expand SkyTofit's label and expand the overall growth hormone market. In addition, We plan to launch SCOTOFA in certain markets in our international indirect region with initial revenue contribution expected to begin in 2024. Turning to Transcontinental PTAs. In the European Union, EMEA CHMP adopted a positive opinion in September. recommending approval of Transcon PTAs as a replacement therapy for adults with chronic hyperparathyroidism. We expect the European Commission final decision on our marketing authorization application this month. If approved, we plan to launch Transcon PTAs in Germany in January 2024. In Germany alone, where the annual cost for currently approved PTH treatment is around 77,000 euros per patient. Our target population is 22,000 chronic hyperparalyzed patients, out of the overall patient population of around 17,000 patients. Our staff is team in Germany that launch SCAR-TROPHE is ready to launch transplant PTH if approved. And EU approval will also provide the basis for marketing authorization and initiation of commercial activities for Transcon PTH in additional markets in our internal market segment, where we expect to launch starting in 2024. And further launches in Europe direct in 2025, following standard price and reimbursement pathways. By following our algorithm for product innovation, we will have taken Transcon PTH from IDEA to expected regulatory approval all in about seven years. In the U.S., all documents have been finalized, and we expect to resubmit the NDA for Transcon PTH for adult with hyperparathyroidism within a week. We expect to know where the FDA has accepted our resubmitted MDA with 30 days from the resubmission date. If accepted, we expect the FDA to notify us at the time where the resubmission is class one or class two, and provide a new PDUFA date. Besides this information, we will not comment further on the resubmission. As with Geithhofer, We continue to build up the science and data behind Transcon PTAs. In September, we announced a post-hoc analysis of Phase 2 and Phase 3 data, demonstrating substantial increase in estimated GFR in adults with hyperpyothyroidism treated with Transcon PTA. These data suggest that treatment with Transcon PTA can reverse impaired kidney function in patients with hyperparathyroidism. Turning to Transcon CMP, this is our third endocrine rare disease product candidate. Following our End of Phase II meeting with U.S. and EU regulatory agencies, we have lined on the pathway to potentially receive regulatory approvals in the U.S. and EU. We expect top-line results from our purist phase 3 approach trial with completed enrollment in Q3 in the second half of 2024. We continue to have strong patient retention in our trials, and during the fourth quarter, we will provide an update and share with you one-year follow-up data with the open label extension portion of ACCOMPLISH. We believe the strong retention in our clinical trial is a result of additional benefit of transplant CLP in addition to height improvements. as we have further evaluated the science behind achondroplasia and our own data. We now believe that achondroplasia is a disease of both skeletal growth and muscle function, and that the continuous exposure to the CMP enabled by Transcon-CMP may be able to address both elements. Coming update, we will disclose these additional potential benefits of Transcon-CMP in addition to height. If we are right, that is correct that achondroplasia is a disease of both skeletal growth and muscle function. This means that Transcon-CMP could potentially offer value for adults living with achondroplasia. who experience muscle fatigue or other medical and quality of life impacts that may be potentially addressable with constant exposure to CMP. We are in a constructive dialogue with regulators on how best to evaluate the potential impact on transplant CMP on comorbidities. quality of life, and other important aspects of achondroplasia, in addition to height, to support an indication for treatment of achondroplasia. While our key focus in the treatment of achondroplasia is to address the comorbidities that are associated with this disease, we believe an even more effective way to address height, if needed or desired, could be CMP in combination with Gotamo. We believe that this combination therapy may provide greater analyzed height velocity and CMP alone, and at the same time address the comorbidity of acromioplasia. Our previously presented preclinical data demonstrate the additive effect of combining transcom-CMP and growth hormone in animal models. assisting with stimulation of different growth-promoting signal pathways in the growth plate. Supporting this idea, a group out of Osaka University in Japan presented a poster during last month's ASBMR, showing that a large group of 41 agronomical children treated with growth hormone demonstrated first-year analyzed high velocity of around 7.4 cm with sustained growth benefit through five years of treatment. To explore this concept, we plan to submit an IMD amendment or similar to initiate a combination trial of Transcon-CMP and Skytroper by the end of this year. Moving to Oncology. For Transcon IL-2 Beta Gamma, we recently reported new data from the, I believe, trial of Transcon IL-2 Beta Gamma as monotherapy and in combination with Tempro at ESMO. These data confirmed that Transcon IL-2 Beta Gamma dose every three weeks demonstrated clinical activity as monotherapy or combination therapy, of course, late-line heavily pre-treated patients in multiple tumor types. further strengthening our confidence in its best-in-class potential. In two out of three small lung cancer patients treated with combination therapy in the trial, a confirmed partial response and unconfirmed complete response in the first tumor assessment of an ongoing patient were observed. We believe these data are intriguing, despite the very small sample size, considering the treatment history of the responders and the substantial unmet medical need. Enrollment is ongoing in the indication-specific cohort of AIP, I believe, where we are now enrolling 20 to 40 patients in each indication, and we expect interim results in the second half of 2024. In summary, with growing revenue, maturing of our pipeline, we continue to progress to our goal of becoming profitable. With our vision 3x3 on track to be achieved in 2025, we are preparing for our next vision for growth to 2030. In our next vision, which I look forward to sharing with you at the beginning of 2024, We will work to level our fully integrated capability to become the leading endocrinology rare disease company, taking product from concept out to patient on a global scale with a highly productive organization. In other areas where we believe Transcom can deliver best-in-class product candidates, as we have in oncology and ophthalmology, we plan to pursue partnerships over business models to take out our product candidates to late-stage development to commercialization. Such future partnerships in oncology and ophthalmology, along with the maturation of our endocrinology program, should result in lower expenses in the coming years. By staying focused on achieving valued market leadership globally for our endocrinology rare disease portfolio, we believe Ascendant will deliver sustainable value over the long term for patients, shareholders, and society. I will now turn to call over to Scott for a financial review before we open for questions.