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June 9, 2025 COACH Trial Interim Topline Week 26 Data Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution.
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This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, such as statements regarding TransCon hGH’s ability to complement TransCon CNP’s holistic treatment of achondroplasia; the potential for the combination of TransCon CNP + TransCon hGH to further transform the treatment of achondroplasia and boost growth ~3x above that observed with CNP monotherapies; the expected timing of Week 52 data from the COACH Trial; our plan to begin a Phase 3 trial in Q4 2025; our planned new trials to support TransCon CNP + TransCon hGH treatment in additional indications such as hypochondroplasia; our ability to become the leader in growth disorders and musculoskeletal health; plans and objectives of management for future operations and commercialization activities; and future results of current and anticipated products and product candidates, are forward-looking statements. These forward-looking statements are based on our current expectations and beliefs, as well as assumptions concerning future events. These statements involve known and unknown risks, uncertainties and other factors that could cause our actual results to differ materially from the results discussed in the forward-looking statements. These risks, uncertainties and other factors are more fully described in our reports filed with or submitted to the Securities and Exchange Commission (SEC), including, without limitation, our most recent Annual Report on Form 20-F filed with the SEC on February 12, 2025, particularly in the sections titled “Risk Factors” and “Operating and Financial Review and Prospects.” In light of the significant uncertainties in our forward-looking statements, you should not place undue reliance on these statements or regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified timeframe, or at all. Any forward-looking statement made by us in this presentation speaks only as of the date of this presentation and represents our estimates and assumptions only as of the date of this presentation. Except as required by law, we assume no obligation to update these statements publicly, whether as a result of new information, future events, changed circumstances or otherwise after the date of this presentation. This presentation concerns anticipated products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration or any other foreign regulatory authority. These anticipated products are currently limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. Cautionary Note on Forward-Looking Statements © 2025 Ascendis Pharma. Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, and TransCon are trademarks owned by the Ascendis Pharma group. Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution.2
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• COACH is the first clinical trial to evaluate once-weekly TransCon CNP and once-weekly TransCon hGH combination treatment in children with achondroplasia (ACH) • Interim topline Week 26 data from the Phase 2 COACH Trial demonstrated: ◦ For TransCon CNP treatment-naïve cohort, mean annualized growth velocity (AGV) was 9.14 cm/year with an improvement in mean ACH height Z-score of +0.53 over 26 weeks ◦ For TransCon CNP-treated cohort, mean AGV was 8.25 cm/year with an improvement in mean ACH height Z-score of +0.44 over 26 weeks • Children treated with TransCon hGH and TransCon CNP demonstrated accelerated improvement in body proportionality at Week 26, aligning with the increase in linear growth • Bone age advanced in line with chronologic age • Safety and tolerability data were consistent with those observed for TransCon hGH and TransCon CNP monotherapies; combination treatment was generally well tolerated, with generally mild treatment-emergent adverse events (TEAEs) Executive Summary Data on file, Ascendis Pharma 2025. TransCon hGH boosted treatment benefits of TransCon CNP with an observed safety profile consistent with monotherapies Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution.3
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Expanding the Treatment Paradigm 1. Blum WF, et al. Endocr Connect. 2018;7(6):R212-R222. 2. Devesa J, et al. Clin Med Insights Endocrinol Diabetes. 2016 Oct 12;9:47-71. 3. Rintz E, et al. Int J Mol Sci. 2022; 23(11). 4. Krejci P, et al. PLoS One. 2008; 3(12): e3961. 5. Horton WA, et al. Lancet. 2007; 370(9582):162–72. 6. Miyazawa T, et al. Endocrinology. 2002; 143(9): 3604-10. 7. Yasoda A, et al. Nature medicine. 2004; 10(1): 80-6. TransCon CNP releases the brake Press Accelerator Lift Brake Resting zone Pre-hypertrophic zone Direct effects of GH: Recruitment of stem cells Direct/indirect effects of GH: Chondrocytes increase in numbers Stimulatory effect of CNP: Release the FGFR3-induced BRAKE Proliferative zone Hypertrophic zone GH/CNP exert different effects on the Growth Plate1-7 Calcification zone Ossification zone Indirect effects of GH: Chondrocytes grow and differentiate Figure adapted from: Šromová, V, et al. Cells 2023, 12, 2576. In achondroplasia, overactive FGFR3 signaling acts as a BRAKE, inhibiting bone growth3,4 TransCon CNP releases the brake enabling GH to ACCELERATE outcomes + • TransCon hGH expected to complement TransCon CNP’s holistic treatment of achondroplasia, combining distinct modes of action TransCon hGH presses the accelerator Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution. The combination of TransCon CNP + TransCon hGH could further transform the treatment of achondroplasia 4
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First Phase 2 Combination Trial of CNP + hGH in Children with Achondroplasia Data on file, Ascendis Pharma 2025. Primary Efficacy Objective • Evaluate effect of combination treatment with TransCon CNP and TransCon hGH on linear growth compared to TransCon CNP alone Population • Children with achondroplasia, aged 2-11 years, with open epiphyses Treatment • TransCon CNP 100 µg/kg/week + TransCon hGH 0.30 mg hGH/kg/week Primary Efficacy Endpoint • Annualized growth velocity (AGV) at Week 52 Secondary Endpoints • Change from baseline in height Z-score • AGV over time • Upper to lower body segment ratio (body proportionality) Safety Endpoints • Treatment-emergent AEs, including injection site reactions N=12 TransCon CNP treatment-naïve cohort N=9 TransCon CNP-treated cohort Week 26 Interim Analysis Week 52 Primary Analysis TransCon CNP-treated in ACcomplisH/AttaCH Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution.5
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Full analysis set at COACH screening TransCon CNP Treatment-Naïve Cohort (N=12) TransCon CNP-Treated Cohort (N=9) Age at screening, years, mean (min, max) 4.67 (1, 9) 7.89 (5, 10) Age group, n (%) < 5 years 6 (50.0) 0 5 to < 8 years 5 (41.7) 3 (33.3) ≥ 8 years 1 (8.3) 6 (66.7) Sex, n (%) Male 8 (66.7) 6 (66.7) Female 4 (33.3) 3 (33.3) Genetic variant, n (%) 1138G>A 11 (91.7) 8 (88.9) 1138G>C 0 1 (11.1) 1144G>A 1 (8.3) 0 Demographics and Baseline Characteristics (1/2) Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2025. 6
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Full analysis set at COACH screening TransCon CNP Treatment-Naive Cohort (N=12) TransCon CNP-Treated Cohort (N=9) Age at screening, years, mean (min, max) 4.67 (1, 9) 7.89 (5, 10) Years of exposure to TransCon CNP 100 µg/kg/wk, mean (range) Not Applicable 2.56 (2.30, 2.95) AGV (cm/year), mean (SD) 4.92 (2.18) 5.14 (0.53) ACH-specific* height Z-score, mean (SD) 0.46 (0.70) 1.28 (0.81) CDC-based** height Z-score, mean (SD) -4.46 (0.77) -4.04 (0.66) IGF-1 SDS, mean (SD) -0.63 (1.32) -0.70 (0.48) Demographics and Baseline Characteristics (2/2) Trial population is representative of children with achondroplasia, except for the observed growth benefit in the TransCon CNP-treated cohort Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution. *Hoover-Fong JE, et al. US. OrphanetJ Rare Dis. 2021;16(1):522. **CDC Stature for Age Charts, available at: https://www.cdc.gov/growthcharts/who-growth-charts.htm Data on file, Ascendis Pharma 2025. 7
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Safety Analysis Set All Participants (N=21) n (%) Treatment-Emergent Adverse Event 15 (71.4) Grade 1 (Mild) Grade 2 (Moderate) Grade 3 (Severe) Grade 4 & 5 (Life-threatening or Death) 12 (57.1) 7 (33.3) 1 (4.8) 0 Treatment Related Adverse Events 7 (33.3) Adverse Events (AEs) of Interest Injection site reactions TransCon CNP Injection site reactions TransCon hGH Symptomatic hypotension Fractures 3 (14.3) 4 (19.0) 0 0 Serious Adverse Events (SAEs) 1 (4.8) AE that led to discontinuation of study drug AE that led to withdrawal from trial AE that led to death 0 0 0 Overview of Treatment-Emergent Adverse Events Data on file, Ascendis Pharma 2025. Data cutoff date: 15 May 2025 Safety and tolerability data comparable to monotherapies and TEAEs were generally mild Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution.8
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Safety and Tolerability • Combination treatment showed safety data consistent with those observed for TransCon hGH and TransCon CNP monotherapies, and was generally well tolerated, with generally mild TEAEs • Majority of TEAEs were mild (Grade 1) or moderate (Grade 2) and typical for children of these ages • No TEAEs led to discontinuation of any treatment or withdrawal from the trial and no SAEs were assessed as related to study drugs • No fractures or other bone-related safety events observed • No evidence of hypotensive effect • No deaths were reported • Injection tolerability was consistent with that observed for TransCon hGH and TransCon CNP monotherapies, with all events adjudicated as mild Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2025. 9
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AGV (Mean) ACH Height Z-Score (Mean) Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution. Combination Treatment Growth at Week 26 TransCon CNP Treatment-Naïve Cohort (N=12) 1Gray arrow indicates change from baseline 4.92 9.14 2 3 4 5 6 7 8 9 10 AGV (cm/year) +4.231 Week 26 0.46 0.99 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 ACH Height Z-Score +0.531 Week 26 TransCon CNP + TransCon hGH Baseline TransCon CNP Treatment-Naïve Cohort Baseline Baseline P=0.0063 P=0.0009 TransCon CNP + TransCon hGH treatment demonstrated significant growth improvements Data on file, Ascendis Pharma 2025. 10
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AGV (Mean) ACH Height Z-Score (Mean) Combination Treatment Growth at Week 26 TransCon CNP-Treated Cohort (N=9) 1Gray arrow indicates change from Baseline 2 Baseline AGV calculated as annualized growth over the 52 weeks preceding the COACH Trial 5.14 8.25 2 3 4 5 6 7 8 9 AGV (cm/year) Baseline2 Week 26 +3.101 TransCon CNP + TransCon hGH Baseline TransCon CNP-Treated Cohort Combination treatment demonstrated boosted growth in TransCon CNP-treated children 1.28 1.72 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 ACH Height Z-Score Baseline Week 26 +0.441 P=0.0006 P=0.0002 Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2025. 11
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 0 5 10 15 20 Age (years) AGV (cm/year) 50th 5th 95th 97th 50th 3rd Combination Treatment Mean AGV at Week 26 Adapted from: Hoover-Fong JE, et al. Am J Clin Nutr. 2008 Aug;88(2):364-71. Natural history AGV curves presented for male children; curves for average stature children from 0-3y reflect 10th, 50th, and 90th percentile. 4.92 cm/year Baseline TransCon CNP Treatment-Naïve 9.14 cm/year TransCon CNP Treatment-Naïve 8.25 cm/year TransCon CNP-Treated Achondroplasia Average Stature TransCon CNP + TransCon hGH treatment exceeded AGV 97th percentile of average stature children 5.14 cm/year Baseline TransCon CNP-Treated Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2025. 12
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COACH Body Proportionality at Week 26 -0.08 -0.07 -0.06 -0.05 -0.04 -0.03 -0.02 -0.01 0.00 0.01 0.02 Upper to Lower Body Segment Ratio Change from Baseline (Mean (±SE)) Baseline Week 13 Week 26 TransCon CNP Treatment-Naïve Cohort (N=12) -0.08 -0.07 -0.06 -0.05 -0.04 -0.03 -0.02 -0.01 0.00 0.01 0.02 Baseline Week 13 Week 26 TransCon CNP-Treated Cohort (N=9) TransCon hGH + TransCon CNP treatment demonstrated accelerated improvement in body proportionality, aligning with the increase in linear growth Improvement Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2025. 13
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• Week 26 data demonstrated the potential to boost growth ~3x above that observed with CNP monotherapies over the same period, supporting the scientific rationale for treating with TransCon CNP and TransCon hGH combined • Week 52 data expected in Q4 2025 • Plan to begin Phase 3 trial in Q4 2025 • Ongoing and planned new trials to support TransCon CNP + TransCon hGH treatment in additional indications such as hypochondroplasia Combination Treatment Program Next Steps Data on file, Ascendis Pharma 2025. With once-weekly TransCon hGH and TransCon CNP, we believe Ascendis is well-positioned to be the leader in growth disorders and musculoskeletal health Combination treatment with investigational TransCon CNP and TransCon hGH is investigational. For investor communication only. Not for use in product promotion. Not for further distribution.14
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Thank you