Full Press Release Details
TransCon CNP (navepegritide)
ApproaCH Trial Topline Results September 16, 2024 TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further distribution. Exhibit 99.1
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related to TransCon CNP; our expectations regarding TransCon CNP's potential to meet the need for a treatment addressing the health and quality-of-life complications of achondroplasia; our development plans for TransCon CNP; our ability to
apply our TransCon technology platform to build a leading, fully integrated biopharma company, particularly in the treatment of skeletal dysplasias and growth disorders; 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
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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
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being investigated. TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further distribution. 2024 Ascendis Pharma. Ascendis, Ascendis Pharma, the Ascendis Pharma
logo, the company logo, TransCon, and SKYTROFA are trademarks owned by the Ascendis Pharma group.
Executive Summary The pivotal ApproaCH
Trial in children aged 2-11 years achieved primary objective 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) Children with achondroplasia treated with TransCon CNP exceeded growth rate of general population, providing catch-up growth without
accelerated bone age Other endpoints supportive that TransCon CNP may provide benefits beyond linear growth Treatment with TransCon CNP resulted in numerical improvements in health-related quality of life compared to placebo as observed in several
ACEM domains Patients dosed with TransCon CNP demonstrated statistical improvement in body proportionality compared to baseline TransCon CNP was generally well-tolerated, with low frequency of mild injection site reactions Continued to show safety
results similar to placebo and was well-tolerated, with generally mild TEAEs No evidence of hypotensive effect Injections were generally well tolerated, with low frequency of injection site reactions (0.41 events per patient year), all mild
Once-weekly TransCon CNP has potential to address the needs for an efficacious, safe, tolerable, and convenient treatment TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not
for further distribution. Data on file, Ascendis Pharma 2024.
ApproaCH Pivotal Trial Design:
TransCon CNP in Children with Achondroplasia Ages 2 to 11 years Double-blind, placebo-controlled trial with an open-label extension period 84 children (ages 2 to 11 years) with achondroplasia randomized 2:1 (TransCon CNP:Placebo) 57 Participants
TransCon CNP 100 g/kg/wk TransCon CNP 100 g/kg/wk 27 Participants Placebo TransCon CNP 100 g/kg/wk Week 52 Week 104 Double-Blind Period Open-Label Extension Period Primary Objective Evaluate efficacy of TransCon CNP on annualized
growth velocity (AGV) Secondary Objective Evaluate efficacy of TransCon CNP on height Z-score Evaluate impact of TransCon CNP on health-related QoL Safety Objective Evaluate safety & tolerability of TransCon CNP Sample Size and Stratification 84
randomized participants, stratified by age and sex (aged < 5 years, aged 5 years and female, aged 5 years and male) Countries United States, Canada, Denmark, Ireland, Spain, United Kingdom, Australia, New Zealand Primary Endpoint
Annualized growth velocity (AGV) at Week 52 Secondary Endpoints Change from baseline in height Z-score at Week 52 Change from baseline in SF-10 physical summary score at Week 52 Change from baseline in ACEM-PF, ACEM-DF, ACEM-OSM scores at Week 52
Safety Endpoint Incidence of treatment emergent adverse events (TEAEs) and safety assessments Selected Other Endpoints Bone age Upper- to lower-body segment ratio (proportionality) ACEM-EW Muscle functionality test TransCon CNP is an investigational
product candidate. For investor communication only. Not for use in product promotion. Not for further distribution.
Demographics and Baseline
Characteristics (1/2) Full Analysis Set TransCon CNP (n=57) Placebo (n=27) Overall (N=84) Age (years), mean (SD) 5.6 (2.6) 6.0 (2.7) 5.7 (2.6) Age (years) group, n (%) 2-4 5-7 8 21 (36.8) 26 (45.6) 10 (17.5) 10 (37.0) 10 (37.0) 7 (25.9) 31
(36.9) 36 (42.9) 17 (20.2) Sex, n (%) Female Male 26 (45.6) 31 (54.4) 13 (48.1) 14 (51.9) 39 (46.4) 45 (53.6) Strata (sex, years), n (%) <5 years 5 years and female 5 years and male 21 (36.8) 17 (29.8) 19 (33.3) 10 (37.0) 8 (29.6) 9
(33.3) 31 (36.9) 25 (29.8) 28 (33.3) Region, n (%) United States Europe Rest of world 14 (24.6) 29 (50.9) 14 (24.6) 8 (29.6) 14 (51.9) 5 (18.5) 22 (26.2) 43 (51.2) 19 (22.6) TransCon CNP is an investigational product candidate. For investor
communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024.
Demographics and Baseline
Characteristics (2/2) Full Analysis Set TransCon CNP (n=57) Placebo (n=27) Overall (N=84) Height (cm), mean (SD) 88.9 (12.9) 89.1 (11.5) 89.0 (12.4) ACH-specific height Z-score*, mean (SD) 0.18 (0.92) -0.11 (0.73) 0.09 (0.87) CDC (general
population) height Z-score**, mean (SD) -4.90 (0.98) -5.21 (0.93) -5.00 (0.97) Weight (kg), mean (SD) 17.8 (6.9) 16.8 (4.6) 17.5 (6.3) BMI (kg/m2), mean (SD) 21.7 (2.7) 20.9 (2.8) 21.4 (2.7) Genetic variant causing achondroplasia, n (%) 1138G>A
1138G>C Other 54 (94.7) 3 (5.3) 0 24 (88.9) 0 3 (11.1) 78 (92.9) 3 (3.6) 3 (3.6) Age at ACH diagnosis (years), n (%) Pre-birth At birth 0 to 6 months 6 to 12 months 12 months 15 (26.3) 20 (35.1) 18 (31.6) 2 (3.5) 1 (1.8) 9
(33.3) 6 (22.2) 9 (33.3) 3 (11.1) 0 24 (28.6) 26 (31.0) 27 (32.1) 5 (6.0) 1 (1.2) Well balanced between key baseline demographics such as height, sex, and age TransCon CNP is an investigational product candidate. For investor communication only. Not
for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024. *Hoover-Fong JE, et al. US. Orphanet J Rare Dis. 2021;16(1):522. **https://www.cdc.gov/nccdphp/dnpao/growthcharts/index.htm
Overview of Treatment Emergent Adverse
Events (TEAEs) Safety analysis set TransCon CNP (n=57) n (%) Placebo (n=27) n (%) Any Adverse Event Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 52 (91%) 52 (91%) 16 (28%) 4 (7%) 0 0 26 (96%) 25 (93%) 11 (41%) 1 (4%) 0 0 Any treatment-related adverse
events 12 (21%) 7 (26%) Serious adverse events 3 (5%) 3 (11%) Adverse events of special interest Injection site reactions Fractures Symptomatic hypotension 11 (19%) 11 (19%) 0 0 4 (15%) 4 (15%) 0 0 AE leading to discontinuation of study drug AE
leading to withdrawal from trial AE leading to death 0 0 0 0 0 0 Safety and tolerability results comparable to placebo, with generally mild TEAEs TransCon CNP is an investigational product candidate. For investor communication only. Not for use in
product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024.
TransCon CNP Safety and Tolerability
Results TransCon CNP showed safety results comparable to placebo and was generally well tolerated, with generally mild TEAEs Majority of AEs were mild (Grade 1) or moderate (Grade 2) and typical for children of these ages No AEs led to
discontinuation of TransCon CNP or withdrawal from the trial and no SAEs were assessed as related to TransCon CNP No deaths were reported No fractures or other bone-related safety events observed No evidence of hypotensive effect with TransCon CNP
Injections were generally well tolerated, with low frequency of injection site reactions (0.41 events per patient year), all mild TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product
promotion. Not for further distribution. Data on file, Ascendis Pharma 2024.
Primary Endpoint: Annualized Growth
Velocity at Week 52 TransCon CNP achieved the primary objective, demonstrating superiority over placebo ANCOVA model. TransCon CNP (n=57) Placebo (n=27) LS Mean AGV (cm/yr) at Week 52 5.89 4.41 LS Mean Difference [95% CI] (TransCon CNP vs. Placebo)
1.49 [1.05, 1.93] p-value (TransCon CNP vs. Placebo) p <0.0001 TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma
3.95 5.95 3.75 4.29 Observed
Annualized Growth Velocity Over 52 Weeks Children treated with TransCon CNP increased their AGV 2.00 cm/year over 52 weeks (Observed values) Annualized Growth Velocity (cm/year) Mean ( SE) TransCon CNP is an investigational product candidate.
For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024.
TransCon CNP demonstrated superior
AGV compared to placebo in both age groups Sub-Group Analyses: Primary Endpoint by Age Groups ANCOVA model. Sub-group analyses by age 2 to <5 years 5-11 years TransCon CNP (n=21) Placebo (n=10) TransCon CNP (n=36) Placebo (n=17) LS Mean AGV
(cm/yr) at Week 52 6.07 5.06 5.79 4.02 LS Mean Difference [95% CI], p-value (TransCon CNP vs. Placebo) 1.02 [0.29, 1.74] 1.78 [1.22, 2.33] p-value (TransCon CNP vs. Placebo) p=0.0084 p<0.0001 TransCon CNP is an investigational product candidate.
For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024. ANCOVA model.
TransCon CNP demonstrated
significant change from baseline AGV compared to placebo by age group Sub-Group Analyses: Change from Baseline AGV by Age Group ANCOVA model. Sub-group analyses by age 2 to <5 years 5-11 years TransCon CNP (n=19) Placebo (n=10) TransCon CNP
(n=35) Placebo (n=17) Change from Baseline AGV at Week 52, LS Mean 1.57 0.43 2.29 0.52 Treatment Difference, [95% CI], (TransCon CNP vs. Placebo) 1.15 [0.40, 1.89] 1.78 [1.20, 2.35] p-value (TransCon CNP vs. Placebo) p=0.0047 p<0.0001 TransCon
CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024. ANCOVA model.
Secondary Endpoint: Change from
Baseline in Height Z-score at Week 52 ACH Height Z-Score TransCon CNP (n=57) Placebo (n=27) LS Mean CFB at Week 52 0.30 0.01 LS Mean Difference [95% CI] (TransCon CNP vs. Placebo) 0.28 [0.18, 0.39] p-value (TransCon CNP vs. Placebo) <0.0001 CDC
Height Z-score TransCon CNP (n=55) Placebo (n=27) LS Mean CFB at Week 52 0.15 -0.15 LS Mean Diff [95% CI] (TransCon CNP vs. Placebo) 0.30 [0.14, 0.45] p-value (TransCon CNP vs. Placebo) 0.0003 TransCon CNP achieved secondary objective demonstrating
superiority over placebo TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024. ANCOVA model.
Change from Baseline in Height
Z-score Over 52 Weeks ACH* Height Z-score CDC** Height Z-score Children with achondroplasia treated with TransCon CNP exceeded growth rate of general population, providing catch-up growth without accelerated bone age Change from Baseline Mean
( SE) Change from Baseline Mean ( SE) Visit Visit TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024.
*Hoover-Fong JE, et al. US. Orphanet J Rare Dis. 2021;16(1):522. **https://www.cdc.gov/nccdphp/dnpao/growthcharts/index.htm
Results Beyond Linear Growth In the
total trial population, treatment with TransCon CNP resulted in numerical improvements in health-related quality of life compared to placebo as observed in several ACEM domains At baseline, parents of children generally reported lower burden of
health-related quality of life compared to the ACcomplisH Trial Selected endpoints beyond linear growth: Health-related signs and symptoms and quality of life measures: ACEM-OSM, -PF, -DL, -EW and SF-10 PHS Muscle functionality testing (exploratory
endpoint) Predefined sub-group analyses of ACEM-Physical Functioning demonstrated potential treatment effect, supported by muscle functionality test results ACEM: Achondroplasia Child Experience Measure, -OSM: Observable Signs Measure, -PF: Impact
Physical Functioning, -DL: Impact Daily Living Functioning, -DW:Impact Emotional-Wellbeing, SF-10 PHS: SF-10 Health Survey for Children Physical Summary Score For children with health-related QoL burden at baseline a potential treatment effect was
observed across several HRQoL domains of the ACEM measures TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further distribution.
n Least Squares Means
TransCon CNP Placebo 28 13 -9.80 29 12 -7.49 45 24 -3.36 24 11 -9.96 Results in Patients with Reported Health-Related QoL Burden at Baseline* TransCon CNP Better Placebo Better ACEM Observable Signs Measure ACEM Physical Functioning ACEM Daily
Living Functioning ACEM Emotional Well-Being Least Squares Means (95% CI) p=0.05 *Post hoc analysis of data with baseline scores at or above 20. Nominal p-value. TransCon CNP is an investigational product candidate. For investor communication
only. Not for use in product promotion. Not for further distribution. Data on file, Ascendis Pharma 2024. TransCon CNP Better Placebo Better Least Squares Means (95% CI) Total Trial Population Patients with HRQoL Burden 20 at Baseline*
n Least Squares Means
TransCon CNP Placebo 20 10 -11.1 Results in ACEM-PF Predefined Sub-Group Are Supported by Exploratory Muscle Functionality Endpoint TransCon CNP Better Placebo Better ACEM Physical Functioning 5 years p=0.037 *Week 52 Body-weight normalized
torque in Knee Extension test [N*m/kg]; Exploratory end-point in trial subjects 5years at testing. Sub-group age at testing. Nominal p-values. n Least Squares Means TransCon CNP Placebo 24 7 0.20 Placebo Better TransCon CNP Better
Muscle Strength* 5-8 years Least Squares Means (95% CI) Least Squares Means (95% CI) p=0.012 TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further
distribution. Data on file, Ascendis Pharma 2024.
ApproaCH Body Proportionality
Patients dosed with TransCon CNP demonstrated statistical improvement in body proportionality compared to baseline (p=0.02) while placebo was unchanged from baseline (p=0.43) Upper to Lower Body Segment Ratio (Change from Baseline) Mean ( SE)
TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion. Not for further distribution. Nominal p-value. Data on file, Ascendis Pharma 2024. TransCon CNP Placebo
Summary & Next Steps The
pivotal ApproaCH Trial results support the desired target product profile of once-weekly TransCon CNP delivering continuous exposure of CNP Plan to submit New Drug Application to the U.S. FDA for TransCon CNP for treatment of children with
achondroplasia in the first quarter of 2025 Plan to submit a Marketing Authorisation Application for treatment of children with achondroplasia to the European Medicines Agency during the third quarter of 2025 Comprehensive development plans continue
with ongoing and planned trials to support TransCon CNP in additional patient populations Strong retention with all 82 children who completed the double-blind period are continuing in the open-label extension of ApproaCH With once-weekly SKYTROFA
and TransCon CNP, Ascendis is uniquely positioned to become the leader in treatment of skeletal dysplasias and growth disorders TransCon CNP is an investigational product candidate. For investor communication only. Not for use in product promotion.
Not for further distribution.
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