ECE 2024: 2-year results from the Phase 3 PaTHway Trial

Sustained Improvement in Renal Function

With Palopegteriparatide in Adults With

Chronic Hypoparathyroidism: 2-Year

Results From the Phase 3 PaTHway Trial

Presented at ECE on May 12, 2024

Schwarz P, Rejnmark L, Gosmanova E, et al. Oral Presentation at ECE 2024; May 12, 2024; Stockholm, Sweden.

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

Cautionary Note on Forward-Looking Statements

This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, such as statements regarding our products and prospective product candidates; clinical trial results; the expected timing of future clinical trial results; the scope, progress, results and costs of developing our product candidates or any other future product candidates; timing and likelihood of success; plans and objectives of management for future operations; 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, including, without limitation, our most recent Annual

Report on Form 20-F filed with the SEC on February 7, 2024 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 product candidates that are or have been under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration, European Medicines Agency or other foreign regulatory authorities. These product candidates are currently limited by U.S. Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated.

Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, TransCon, and YORVIPATH are trademarks owned by the Ascendis Pharma group. © May 2024 Ascendis Pharma A/S.

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

PTH Therapy for Hypoparathyroidism

• An intact PTH axis maintains normal serum calcium and phosphate homeostasis1,2,3
• PTH promotes normal nerve and muscle function4
• Conventional therapy for hypoparathyroidism (active vitamin D [eg, calcitriol, alfacalcidol], and oral calcium) aims to alleviate hypocalcemic symptoms but fails to restore normal PTH physiology
• PTH replacement therapy for hypoparathyroidism should provide PTH levels within the physiological range and restore downstream calcitriol, promoting independence from conventional therapy and normalizing:
• • Serum and urine biochemistries
  • Skeletal health
  • Quality of life

PTH, parathyroid hormone.

1. Khan AA, et al. J Bone Miner Res. 2022;37:2568-2585. 2. Shoback DM, et al. J Clin Endocrinol Metab. 2016;101(6):2300-2312.

1. Bilezikian JP, et al. J Clin Endocrinol Metab. 2016;101(6):2313-2324. 4. Mannstadt M, et al. Nat Rev Dis Primers. 2017; 3:17055.

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

TransCon® PTH (palopegteriparatide) Design

TransCon

carrier

TransCon linker

Active PTH

Receptor

Renal

clearance

PTH	Linker cleavage under
(inactive)	physiologic conditions

• TransCon PTH is a prodrug of PTH (1-34), administered once daily, with sustained release of active PTH designed to provide PTH levels in the physiological range for 24 hours/day
• TransCon PTH is approved under the brand name YORVIPATH® by the European Commission as a PTH replacement therapy for adults with chronic hypoparathyroidism (YORVIPATH is marketed in Germany and

Austria)

PTH, parathyroid hormone; TransCon, transient conjugation

Karpf DB, et al. J Bone Miner Res. 2020;35(8):1430-1440.

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

TransCon PTH Phase 3 PaTHway Trial Design (NCT04701203)

Screening

≤4 weeks

82 adults with hypoparathyroidism receiving conventional therapy (active vitamin D + calcium)

Co-administered with conventional therapy

Open-Label Extension

Randomization(3:1)

TransCon PTH 18 µg/day, titrated

ParticipantsAll

n = 76 (93%) completed treatment through Week 104

based on algorithm

TransCon PTH

(titrated to optimal dose)

Placebo, titrated based on

algorithm

Double-blind period to Week 26

Week

104

Week 182

Efficacy Endpoints

• Independence from active vitamin Da
• Independence from therapeutic doses of calciumb
• Serum biochemistries

Post Hoc Renal Endpoints

• Estimated glomerular filtration rate (eGFR)c
• • Subgroup analysis by baseline renal function < 60 mL/min/1.73 m2 (impaired) and ≥ 60 mL/min/1.73 m2

Safety and Tolerability Endpoints

• 24-hoururine calcium
• Incidence of Adverse Events, Serious Adverse Events, and Treatment- Related Adverse Events

aIndependence from active vitamin D is defined as a standing dose of active vitamin D equal to zero on the day prior to the week 52 visit

bIndependence from therapeutic doses of calcium is defined as a standing dose of elemental calcium ≤600 mg on the day prior to the week 52 visit

cCalculated according to the Modified Diet in Renal Disease Equation (MDRD): eGFR (mL/min/1.73 m2) = 175 × (serum creatinine mg/dL)-1.154 × (age)-0.203 × 0.742 [if female] × 1.212 [if Black]

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

Independence From Conventional Therapy at Week 104

	All Participants	Baseline eGFR	Baseline eGFR
	< 60 mL/min/1.73 m2	≥ 60 mL/min/1.73 m2
	(N=82)
	(n=23)	(n=59)
Number of participants with data at week 104	76	22	54
Independence from active vitamin D, n (%)	76 (100%)	22 (100%)	54 (100%)
Independence from therapeutic doses of calcium, n (%)	74 (97%)	21 (95%)	53 (98%)

• 97% of participants treated with TransCon PTH achieved independence from conventional therapy at Week 104 of the PaTHway trial
• Efficacy was consistent in subgroups with and without impaired renal function at baseline

Independence defined as a standing dose of active vitamin D equal to zero and elemental calcium ≤600 mg on the day prior to the week 104 visit

Percentages are calculated based on participants who had data on all criteria eGFR, estimated glomerular filtration rate

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

Serum Calcium and Serum Phosphate Through Week 104

Serum Calcium (mmol/L)a Mean (± SD)

3.0

TransCon PTH n=61

Placebo / TransCon PTH n=21

2.5	Normal Range

2.0

Double-blind

1.5	period		Open-label extensionb

Phosphate (mmol/L)	Mean (± SD)
Serum

2.0

1.5

1.0

Double-blind

0.5 period

TransCon PTH n=61

Placebo / TransCon PTH n=21

Normal Range

Open-label extensionb

0

12

26

38

52

78

104

Weeks

0

12

26

38

52

78

104

Weeks

TransCon PTH treatment over 104 weeks maintained serum calcium and phosphate within normal ranges

aAlbumin-adjusted.bAll participants received TransCon PTH during the open-label extension SD, standard deviation Normal ranges (shaded region): albumin-adjusted serum calcium 2.1-2.6 mmol/L; serum phosphate 0.8-1.5 mmol/L

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

Change From Baseline in eGFR Through Week 104

Change(SD)from Baseline	(mL/min/1.73meGFR
	)
	2
Mean	in

25

20

15

10

5

0

-5

-10

All Participants	Baseline eGFR < 60 mL/min/1.73 m2	Baseline eGFR ≥ 60 mL/min/1.73 m2
TransCon PTH n=61	TransCon PTH n=19	TransCon PTH n=42
Placebo / TransCon PTH n=21	Placebo / TransCon PTH n=4	Placebo / TransCon PTH n=17
25		25
20		20
15		15
10		10
5		5

0

0

														-5																		-5
														-10																		-10
Double-blind													Double-blind												Double-blind
period		Open-label extensiona							period			Open-label extensiona						period		Open-label extensiona
0	12	26	38	52	78	104	0	12	26	38	52	78	104	0	12	26	38	52	78	104
							Weeks																	Weeks																Weeks

TransCon PTH treatment resulted in a mean increase in eGFR of 8.9 mL/min/1.73m2 (P<.0001) from baseline to week

52, which was sustained through week 104 with a mean change from baseline of 9.0 mL/min/1.73m2 (P<.0001)

aAll participants received TransCon PTH during the open-label extension. eGFR, estimated glomerular filtration rate; SD, standard deviation

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

Proportion of Participants (%) With ≥ 5 and ≥ 10 mL/min/1.73 m2 Increases in eGFR Through Week 104

				All Participants
	(%)	100
Clinically meaningful	80		64	61			62
Participants		57		52
60
(≥ 5 mL/min/1.73 m2)
	40
increase in eGFR					24
from baseline1,2		20
		0
	(%)	100
	80
≥ 10 mL/min/1.73 m2	Participants	60	43	43	46			38
increase in eGFR
	40					29
from baseline
	20				10
TransCon PTH		0
Placebo			Wk	Wk	Wk	Wk	Wk	Wk
Switch to TransCon PTH			26	52	104	26	52	104
				(n=61)			(n=21)

Baseline eGFR < 60 mL/min/1.73 m2	Baseline eGFR ≥ 60 mL/min/1.73 m2
100			100	100	100
80	74	68	74		80		62
60					60	50	55		53
40					40					41
		25					24
20					20
0					0
100					100
80			75	75	80
60	47	42	53		60	41	43	43
40				40		29
20					20				12	18
		0
0				0

Wk	Wk	Wk	Wk	Wk	Wk	Wk	Wk	Wk	Wk	Wk	Wk
26	52	104	26	52	104	26	52	104	26	52	104
	(n=19)			(n=4)			(n=42)			(n=17)

TransCon PTH treatment was associated with clinically meaningful increases ≥ 5 mL/min/1.73 m2 in

eGFR within 26 weeks that were sustained through week 104 of the PaTHway trial

Wk, week.

1. Mayne TJ, et al. Clin Transplant. 2021;35(7):e14326.
2. Ku E, et al. J Am Soc Nephrol. 2016;27(7):2196-204

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.

24-Hour Urine Calcium Excretion Through Week 104

12

10

8

TransCon PTH		Placebo /		Switch to TransCon PTH
		Placebo participants switched
		to TransCon PTH at week 26
			(open-label extension)

24-Hour Urine Calcium

(mmol/day) 6

Mean (± SE)

4

9.8

7.5

		ULN Men (≤ 7.5 mmol/day) ​
		ULN Women (≤ 6.2 mmol/day)
8.2	7.6	7.3

2

0

5.5

4.6

3.8

5.6	4.6
a

Baseline Week 12 Week 26 Week 52 Week 104

(n=60) (n=50) (n=56) (n=56) (n=43)

Baseline	Week 12	Week 26	Week 52	Week 104
(n=21)	(n=17)	(n=17)	(n=19)	(n=14)

Mean 24-hour urine calcium excretion normalized within 26 weeks and was maintained within the

normal range through week 104 with TransCon PTH treatment

aParticipants randomized to placebo at baseline initiated TransCon PTH treatment at week 26 SE, standard error; ULN, upper limit of normal

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TransCon PTH is an investigational products candidate. For investor communication only. Not for use in product promotion. Not for further distribution.