CNP

— Data demonstrated multiple clinical benefits beyond linear growth —  NDA supported by data from three randomized, double-blind, placebo-controlled clinical trials in children with achondroplasia, with up to three years of open-label extension data —  MAA in EU on track for submission during Q3 2025 COPENHAGEN, Denmark I March 31, 2025 I Ascendis Pharma A/S (Nasdaq: ASND) today announced that it has submitted its New Drug Application (NDA) to the U.S. Food & Drug Administration (FDA) for TransCon CNP (navepegritide) for the treatment of children with achondroplasia. TransCon CNP is an investigational prodrug of C-type natriuretic peptide (CNP) administered once weekly and designed to treat individuals with achondroplasia by providing continuous exposure of active CNP to receptors on tissues throughout the body, including growth plates and skeletal muscle. The filing is based on data from three randomized, double-blind, placebo-controlled clinical trials and up to three years of open-label extension data, including results from the pivotal ApproaCH Trial of children with achondroplasia. “We are pleased to share clinical data with the FDA demonstrating that, in addition to increased growth velocity, treatment with TransCon CNP was associated with reduced health-related burden, stronger muscle function, and straightening of abnormal leg bowing for the majority of treated children,” said Aimee Shu, M.D., Executive Vice President and Chief Medical Officer at Ascendis Pharma. “In addition to once-weekly administration, these outcomes and a safety and tolerability profile comparable to placebo support TransCon CNP’s potential to be recognized as a best-in-class treatment for achondroplasia.” Ascendis is on track to submit its Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) during Q3 2025. About Achondroplasia Achondroplasia is a rare genetic condition arising from a systemic fibroblast growth factor receptor 3 (FGFR3) variant that leads to an imbalance in the effects of the FGFR3 and CNP signaling pathways, estimated to affect more than 250,000 people worldwide. While historically considered a bone growth disorder, the FGFR3 variant seen in achondroplasia is expressed in tissues throughout the body, causing serious muscular, neurological, and cardiorespiratory complications in addition to skeletal dysplasia. Medical complications of achondroplasia vary across different stages of life. Throughout infancy and childhood, observed complications include spinal deformities, enlarged brain ventricles, impaired muscle strength and stamina, hearing deficits and chronic ear infections, upper airway obstructions, sleep-disordered breathing, hip problems, leg bowing, and chronic pain; many of these persist or worsen in adulthood. These medical complications can have detrimental effects on quality of life, physical functioning, and psychosocial function. Individuals with achondroplasia often require multiple surgeries and procedures to alleviate the condition’s many complications. About Ascendis Pharma A/S Ascendis Pharma is a global biopharmaceutical company focused on applying our innovative TransCon technology platform to make a meaningful difference for patients. Guided by our core values of Patients, Science, and Passion, and following our algorithm for product innovation, we apply TransCon to develop new therapies that demonstrate best-in-class potential to address unmet medical needs. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more. SOURCE: Ascendis Pharma

–    TransCon CNP demonstrated AGV superior to placebo with LS mean treatment difference of 1.49 cm/year at Week 52 (p<0.0001) –    For children aged 5-11 years TransCon CNP demonstrated a change from baseline AGV superior to placebo with LS mean treatment difference of 1.78 cm/year at Week 52 (p<0.0001) –    Other endpoints supportive that TransCon CNP may provide benefits beyond linear growth –    TransCon CNP was generally well-tolerated, with low frequency of injection site reactions (0.41 events per patient year), all mild –    Ascendis to host investor conference call Monday, September 16, at 8:00 a.m. E.T. COPENHAGEN, Denmark I September 16, 2024 I Ascendis Pharma A/S (Nasdaq: ASND) today announced topline data from the pivotal double-blind placebo-controlled ApproaCH Trial of TransCon CNP (navepegritide), which included 84 children with achondroplasia (ages 2-11 years) randomized 2:1 (TransCon CNP:placebo). TransCon CNP is an investigational prodrug of C-type natriuretic peptide (CNP) administered once weekly and designed to provide sustained release and continuous exposure of active CNP. In the trial, children treated with once-weekly TransCon CNP demonstrated annualized growth velocity (AGV) superior to placebo. TransCon CNP also demonstrated statistically significant improvements in other growth parameters, including height Z-score and change from baseline AGV. “Results of this pivotal trial demonstrate that once-weekly TransCon CNP can, if approved, address the need for an efficacious, safe, tolerable, and convenient treatment for children with achondroplasia,” said Ravi Savarirayan, M.D., at the Murdoch Children’s Research Center (Australia) and an investigator in the ApproaCH Trial. “I am excited about the possibilities TransCon CNP presents for a potential new treatment option for these children that will allow decreased injection frequency, improved compliance, and reduced caregiver burden.” “TransCon CNP-treated children with achondroplasia exceeded the growth rate of the general population, suggesting that once-weekly TransCon CNP provides catch-up growth with safety and tolerability results comparable to placebo with a low incidence of injection-site reactions,” said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer. “With SKYTROFA ® and TransCon CNP, Ascendis is uniquely positioned to become the leader in the treatment of skeletal dysplasias and growth disorders.” Highlights of the ApproaCH Trial Topline Data Primary Endpoint AGV Change from Baseline Secondary Endpoints Selected Other Endpoints Safety Summary As of today, all 82 children who completed the double-blind period are continuing in the open-label extension of the ApproaCH Trial. “On behalf of everyone at Ascendis, I want to thank the study participants, families, and clinical investigators contributing to the efforts to improve treatment options for individuals living with achondroplasia,” said Aimee Shu, M.D., Ascendis Pharma’s Senior Vice President of Clinical Development, Endocrine & Rare Disease. “These data support our aspirations for TransCon CNP, and we look forward to working with regulatory authorities as we take the next steps to advance TransCon CNP as a potential new treatment option.” Ascendis plans to submit a New Drug Application (NDA) to the U.S. Food & Drug Administration for TransCon CNP for the treatment of children with achondroplasia during the first quarter of 2025 and a Marketing Authorisation Application (MAA) for the treatment of children with achondroplasia to the European Medicines Agency during the third quarter of 2025. ApproaCH is a pivotal, multicenter, randomized, double-blind, placebo-controlled trial of once-weekly TransCon CNP versus placebo in 84 children with achondroplasia ages 2-11 years old. Patients were randomized 2:1 to receive TransCon CNP or placebo for 52 weeks at the 100μg/kg/week dose in the double-blind period, after which all participants could choose to receive TransCon CNP in an ongoing open-label extension at the 100μg/kg/week dose. A slide presentation with these data can be found on the Investor Relations & News section of the Ascendis Pharma website: https://investors.ascendispharma.com . Conference Call & Webcast Information Ascendis Pharma will host a conference call and webcast on Monday, September 16, 2024, at 8:00 am Eastern Time (ET) to discuss the pivotal ApproaCH Trial results. Those who would like to participate may access the live webcast here , or register in advance for the teleconference here . The link to the live webcast will also be available on the Ascendis Pharma Investors & News website at https://investors.ascendispharma.com. A replay of the webcast will be available on this section of the Ascendis Pharma website shortly after conclusion of the event for 30 days. About Ascendis Pharma A/S Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients’ lives. Guided by its core values of Patients, Science, and Passion, Ascendis uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more. SOURCE: Ascendis Pharma

• Data demonstrate significant improvements in well-being and physical functioning compared to placebo in patients treated for 1 year with TransCon CNP at the pivotal 100μg/kg/week dose • Improvements could not be explained by changes in linear growth only, supporting a potential additional direct treatment effect of TransCon CNP beyond linear growth COPENHAGEN, Denmark, June 24, 2024 (GLOBE NEWSWIRE) -- Ascendis Pharma, Inc. (Nasdaq: ASND) today announced the oral presentation of data from its Phase 2 ACcomplisH Trial of TransCon CNP (navepegritide) in children aged 2 to 10 years old with achondroplasia by Ravi Savarirayan, M.D., Murdoch Children’s Research Center (Australia), during ICCBH 2024, the International Conference on Children’s Bone Health being held in Salzburg, Austria. The data showed that patients treated for one year at the pivotal 100μg/kg/week dose demonstrated significant improvements in well-being and physical functioning compared to placebo. These improvements could not be explained by changes in linear growth only, supporting a potential additional direct treatment effect of TransCon CNP beyond linear growth. “Once-weekly TransCon CNP has demonstrated a positive impact on linear growth with a favorable safety profile, as well as benefits beyond growth,” said Dr. Savarirayan. “As the first investigational pharmaceutical treatment for achondroplasia to demonstrate statistically significant improvements compared to placebo in health-related quality of life measures, TransCon CNP at the pivotal dose has potential to meet the need for a treatment addressing the health and quality-of-life complications of this condition.” TransCon CNP is an investigational prodrug of C-type natriuretic peptide (CNP) administered once weekly, designed to provide sustained release of active CNP. ACcomplisH is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial of once-weekly TransCon CNP versus placebo in 57 children with achondroplasia (aged 2-10 years old). Patients were randomized 3:1 to receive TransCon CNP across 4 dose-escalation cohorts or placebo for 52 weeks, after which participants could receive TransCon CNP in an ongoing open-label extension at the 100μg/kg/week dose. Health-related quality of life assessments compared 52-week results from patients whose initial TransCon CNP dose was 100μg/kg/week (the pivotal trial dose) with results from the pooled placebo group in the randomized period. Of the 57 participants, 56 continue with open-label treatment. Statistically significant improvements were observed for various exploratory endpoints including Daily Living Functioning (p=0.047; n=16; 13 [treated;placebo]) and Emotional Well-Being (p=0.045; n=13;9) domains of the Achondroplasia Child Experience Measure-Impact (ACEM) assessment, and the SF-10 Physical Summary among participants 5 years of age or older (p=0.002; n=9;5). Growth across the full trial population (n=57) on TransCon CNP at the 100μg/kg/week dose for 52 weeks was consistent with results from this dose cohort during the randomized period. No new safety signals were observed, and no serious adverse events related to the study drug were reported. Most treatment-emergent adverse events (TEAEs) were Grade 1-2, with a low frequency of injection site reactions. About Ascendis Pharma A/S Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients’ lives. Guided by its core values of Patients, Science, and Passion, Ascendis uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding Ascendis’ future operations, plans and objectives of management are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to (i) improvements in well-being and physical functioning supporting a potential additional direct treatment effect of TransCon CNP, (ii) TransCon CNP’s potential to meet the need for a treatment addressing the health and quality-of-life complications of achondroplasia, (iii) Ascendis’ ability to apply its TransCon technology platform to build a leading, fully integrated biopharma company, and (iv) Ascendis’ use of its TransCon technologies to create new and potentially best-in-class therapies. Ascendis may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions, expectations, and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Ascendis makes, including the following: dependence on third party manufacturers, distributors and service providers for Ascendis’ products and product candidates; unforeseen safety or efficacy results in Ascendis’ development programs or on-market products; unforeseen expenses related to commercialization of any approved Ascendis products; unforeseen expenses related to Ascendis’ development programs; unforeseen selling, general and administrative expenses, other research and development expenses and Ascendis’ business generally; delays in the development of its programs related to manufacturing, regulatory requirements, speed of patient recruitment or other unforeseen delays; Ascendis’ ability to obtain additional funding, if needed, to support its business activities; the impact of international economic, political, legal, compliance, social and business factors. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ascendis’ business in general, see Ascendis’ Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (SEC) on February 7, 2024, and Ascendis’ other future reports filed with, or submitted to, the SEC. Forward-looking statements do not reflect the potential impact of any future licensing, collaborations, acquisitions, mergers, dispositions, joint ventures, or investments that Ascendis may enter into or make. Ascendis does not assume any obligation to update any forward-looking statements, except as required by law. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, and TransCon are trademarks owned by the Ascendis Pharma group. © June 2024 Ascendis Pharma A/S. Investor Contacts: Media Contact: Tim Lee Ascendis Pharma +1 (650) 374-6343 tle@ascendispharma.com ir@ascendispharma.com Patti Bank ICR Westwicke +1 (415) 513-1284 patti.bank@westwicke.com Melinda Baker Ascendis Pharma +1 (650) 709-8875 media@ascendispharma.com