Ascendis Pharma A/S Stock

Ascendis Pharma A/S, together with its subsidiaries, operates as an integrated, global biopharma company.

The company’s products and product candidates combine its TransCon technologies with clinically validated parent drugs and pathways, with the intention of optimizing efficacy, safety, tolerability and convenience.

The company applies these technologies in combination with clinically validated parent drugs or pathways using the company’s algorithm with the intention of creating product candidates with the potential to be best-in-class. The company plans to apply this algorithm for product innovation to expand the company’s pipeline with Endocrinology Rare Disease product opportunities in large addressable markets.

The company has two marketed products and a diversified portfolio of five product candidates in clinical development in the areas of endocrinology rare diseases and oncology, and the company is working to apply its TransCon technology platform in additional therapeutic areas, such as the glucagon-like peptide 1 (‘GLP-1’) class where the company has designed a best-in-class, once-monthly program.

SKYTROFA – The company’s first marketed product is SKYTROFA (lonapegsomatropin-tcgd), developed as TransCon Growth Hormone (‘TransCon hGH’), which received regulatory approval in the United States for the treatment of pediatric patients one year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone, also known as growth hormone deficiency (‘GHD’). TransCon hGH is now commercially available for prescription in the United States under its brand name SKYTROFA (lonapegsomatropin-tcgd). In addition, TransCon hGH was granted marketing authorization in the European Union (‘EU’) as SKYTROFA (lonapegsomatropin), a once-weekly subcutaneous injection for the treatment of children and adolescents ages 3 to 18 years with growth failure due to insufficient secretion of endogenous growth hormone. SKYTROFA has been commercially available for prescription in Germany since September 2023.

YORVIPATH – The company’s second marketed product is YORVIPATH (palopegteriparatide), developed as TransCon PTH. In the EU, YORVIPATH was granted marketing authorization as a once-daily subcutaneous injection for the treatment of adults with chronic hypoparathyroidism. YORVIPATH has been commercially available for prescription in Germany and Austria since January 2024.

Endocrinology Rare Disease Pipeline – The company is developing three product candidates in its Endocrinology Rare Disease portfolio spanning multiple indications and geographies. These include TransCon hGH for pediatric GHD, adult GHD, and Turner syndrome; TransCon PTH for adults with chronic hypoparathyroidism; and TransCon CNP (navepegritide) for infants and children with achondroplasia.

Oncology – In Oncology, the company is leveraging its TransCon technologies with the goal of enhancing the anti-tumor effects of clinically-validated parent drugs and pathways and to provide sustained modulation of tumor microenvironments and activate cytotoxic immune cells. The company has initiated clinical development of two product candidates: TransCon TLR7/8 Agonist, an investigational, long-acting prodrug of resiquimod, a small molecule agonist of Toll like receptors (‘TLR’) 7 and 8 for intratumoral delivery and TransCon IL-2 b/g for systemic delivery, which is designed for prolonged exposure to an IL-2 variant that selectively activates the IL-2 b/g, with minimal binding to IL-2Ra. The company’s clinical development program for these product candidates also includes evaluation of them as a potential combination therapy.

Ophthalmology - In January 2023, the company announced Ophthalmology as its third independent therapeutic area of focus for the company’s TransCon technologies. In January 2024, the company announced the formation of Eyconis, Inc., with institutional investors and entered into an exclusive license agreement with Eyconis to develop and commercialize TransCon ophthalmology products globally. The company received an equity position in the newly formed company, and the company is eligible to receive future milestone payments plus single digit royalties on global net sales of commercialized products, if any.

The company maintained an intellectual property portfolio comprising over 300 issued patents and over 550 patent applications as of December 31, 2023, which includes patents and patent applications applicable to the company’s product candidates with claims directed to composition of matter, process, formulation and/or methods-of-use for the company’s product candidates, including a product-specific device and core TransCon technologies. Other than the rights the company has granted to VISEN Pharmaceuticals (‘VISEN’), Teijin Limited, and Eyconis, the company holds worldwide rights to its TransCon technologies and, other than the company’s royalty financing arrangement with Royalty Pharma, the company owes no third-party royalty or milestone payment obligations with respect to the company’s TransCon technologies, TransCon hGH or any of the company’s other product candidates.

Global Commercialization Strategy

The company is establishing a global presence to commercialize TransCon product candidates, if approved, to address patients' unmet medical needs.

In the U.S., the company has established a multi-faceted organization to support the ongoing commercialization of SKYTROFA, which will also serve as the foundation for future Endocrinology Rare Disease product launches in the U.S.

In Europe, the company is expanding its presence by building integrated organizations in select countries, which the company calls Europe Direct, beginning with Germany, where the company has launched SKYTROFA and YORVIPATH. The company is establishing other Europe Direct organizations to service country clusters, including DACH (Germany, Austria, and Switzerland), France & BeNeLux (Belgium, the Netherlands, and Luxembourg), Iberia (Portugal and Spain), Italy, Nordics (Denmark, Norway, Sweden, Iceland, and Finland), and the United Kingdom & Ireland.

Beyond the U.S. and Europe Direct, the company is expanding global reach for its Endocrinology Rare Disease programs through exclusive distribution agreements with geographic market leaders, which the company calls International Markets. The company has three such regional agreements established as of January 2024:

Specialised Therapeutics Asia Pte Ltd. (Australia, New Zealand, Singapore, Malaysia, Brunei, Thailand, and Vietnam).

Er-Kim (Central & Eastern Europe and Turkey).

Vector Pharma FZCO (Saudi Arabia, the United Arab Emirates, Kuwait, Oman, Qatar, and Bahrain).

Finally, the company is making its products commercially available in select markets through exclusive license agreements with partners with local expertise and infrastructure. The company plans to also make its product candidates commercially available, if approved, through these exclusive license agreements. In China, VISEN has exclusive license rights to develop and commercialize TransCon hGH, TransCon PTH, and TransCon CNP. In Japan, Teijin has exclusive license rights to develop and commercialize TransCon hGH, TransCon PTH, and TransCon CNP.

TransCon Technologies

The company’s TransCon technologies are designed to combine the benefits of conventional prodrug and sustained release technologies to solve the fundamental limitations seen in other approaches to extending duration of a drug’s action in the body, with the intentionforf developing highly differentiated product candidates based on efficacy, safety, tolerability and convenience.

TransCon molecules can have up to three components: a parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic pH and temperature conditions initiate the release of the active, unmodified parent drug in a predictable release manner. Depending upon the type of TransCon carrier the company employs, the company can design its TransCon prodrugs for sustained localized or systemic delivery.

TransCon Technology Components

TransCon Carriers

The company’s TransCon technologies incorporate two carrier platforms that can be used to provide sustained localized or systemic drug exposure. These biocompatible carrier platforms include the company’s TransCon systemic carriers and TransCon localized carriers (self-eliminating hydrogels). The company’s carriers inactivate and protect the drug through a shielding effect, which may prevent rapid excretion and degradation of the parent drug and enable benefits that include improved injection site tolerability, reduced systemic adverse effects, and low immunogenicity.

Systemic – The company’s TransCon systemic carriers are used to provide systemic drug exposure and are based on soluble compounds, such as methoxy polyethylene glycol (‘mPEG’) or other natural or synthetic polymers. Prodrugs created using the company’s systemic carriers are readily absorbed into the bloodstream after administration, thus minimizing exposure of the subcutaneous tissue to active drug, which may improve injection site tolerability. TransCon hGH, TransCon PTH, and TransCon CNP utilize mPEG as a carrier molecule. mPEG is widely used to improve the pharmacokinetic or pharmacodynamic properties of marketed therapeutics. Below is an illustration of the company’s systemic carrier:

Localized – The company’s TransCon localized carriers include TransCon hydrogels based on PEG, hyaluronic acid, or other biopolymers. TransCon hydrogel is designed to self-eliminate to soluble, biocompatible molecules after the drug payload has been released. When applied for localized delivery, the TransCon hydrogel enables the release of a parent drug at high local concentrations within the target area while minimizing systemic exposure. This may widen the therapeutic window for parent drugs that suffer from significant systemic side effects and toxicities, facilitating the development of highly efficacious product candidates with improved safety and tolerability profiles.

In 2023, the company developed a novel TransCon prolongation technology. The new TransCon technology may support expansion of TransCon technology into new therapeutic areas.

TransCon Linkers

The company’s reversible TransCon linkers are designed to enable the transient conjugation of a broad range of therapeutics, including proteins, peptides and small molecules, to the company’s TransCon carriers. The company has a large library of TransCon linkers that may be applicable to various types of parent drugs, and that can be tailored to potentially achieve half-life extension enabling daily, weekly, monthly, and half-yearly dosing and to customize the potential pharmacokinetic profile for each individual product candidate with the goal of optimizing the potential therapeutic effect. TransCon linkers are self-cleaving through a process called intra-molecular assisted cleavage, which causes the linker to release the unmodified parent drug. The company can tailor the release properties of the linker to a given therapeutic indication and parent drug by modifying the linker structures. The self-cleaving process of the company’s linker avoids many of the shortcomings of conventional prodrug technologies, which often depend on metabolic processes, such as enzymatic degradation, to convert the prodrug into the active drug. The company’s TransCon linkers are designed to predictably release an unmodified active parent drug at predetermined rates governed by physiological pH and temperature conditions, which are tightly regulated in the body. Consequently, the company can design its prodrugs to release the unmodified parent drug at predictable rates.

Parent Drugs

The company’s TransCon technologies are applicable across a broad range of therapeutic classes and are used to create potentially best-in-class long-acting product candidates based on proteins, peptides and small molecules. By primarily focusing on biological targets that have been clinically validated, the company can leverage available knowledge regarding a target’s activity. Based on this selective approach, the company knows what drug levels must be maintained in the body for optimal efficacy and safety, and the company can design the release half-life and dosing frequency of the company’s TransCon prodrugs to maintain these levels to achieve the desired pharmacological effect. The company moves a product candidate into development after it demonstrates the desired profile in non-clinical models. Furthermore, based on the established translational relationships between preclinical animal models and clinical efficacy, experimental results generated in animal models are highly predictive of clinical results and reduce the development risk for the company’s TransCon prodrugs. This strategy is designed to reduce risk and increase productivity.

TransCon Products – Endocrinology Rare Disease

TransCon Growth Hormone (hGH) for pediatric GHD

TransCon hGH, marketed under the brand name SKYTROFA (lonapegsomatropin-tcgd), received regulatory approval in the U.S. for the treatment of pediatric patients one year and older who weigh at least 11.5 kg and have growth failure due to inadequate secretion of endogenous growth hormone, also known as growth hormone deficiency. SKYTROFA has been commercially available for prescription in the United States since October 2021. In the EU, the company received marketing authorization for TransCon hGH – known by its brand name SKYTROFA (lonapegsomatropin) – as a once-weekly subcutaneous injection for the treatment of children and adolescents ages 3 to 18 years with growth failure due to insufficient secretion of endogenous growth hormone. SKYTROFA has been commercially available for prescription in Germany since September 2023.

In September 2023, the company announced topline results from the completed enliGHten Trial, an open-label extension trial evaluating the long-term safety and efficacy of TransCon hGH as a once-weekly treatment for children and adolescents with growth hormone deficiency. The enliGHten Trial enrolled 298 participants (mean age 10.3 years) from the Phase 3 heiGHt Trial of treatment-naïve pediatric GHD patients and the Phase 3 fliGHt Trial of pediatric GHD patients switching from daily somatropin treatment. Patients in these trials received a total of up to 6 years of treatment with TransCon hGH. At the time of the enliGHten Trial closure, 81 participants were designated as treatment completers, based on their physician’s determination that treatment for pediatric GHD was no longer required. Of these treatment completers, 59% met or exceeded their average parental height standard deviation score (‘SDS’), with mean TransCon hGH treatment duration of 3.2 years.

Clinical Trial of TransCon hGH in Japanese Pediatric GHD

In the company’s ongoing Phase 3 riGHt Trial, the company is evaluating TransCon hGH as a treatment in Japanese children with GHD. The primary objective of the riGHt Trial is to evaluate and compare the annualized height velocity of approximately 40 Japanese prepubertal children with GHD treated with once-weekly TransCon hGH to that of children treated with a commercially available daily hGH formulation at 52 weeks. Enrollment in the riGHt trial was completed during the fourth quarter of 2023.

Proprietary Auto-injector

SKYTROFA includes the SKYTROFA Auto-Injector and cartridges. The auto-injector provides for room temperature storage, includes an empty-all design, and is expected to last for at least four years. The device has a single, low-volume injection for the majority of patients of less than 0.6 mL and requires a thin, 31-gauge needle that is only 4 millimeters in length, which is comparable to needles used to administer daily hGH. The company is also working on strategies that will enable the auto-injector to integrate with the digital healthcare system, including Bluetooth connectivity features to allow for easy tracking of dosing adherence over time.

TransCon Product Candidates – Endocrinology Rare Diseases

TransCon Growth Hormone (hGH) for Other Indications

Clinical Development in Adults

The company is conducting the foresiGHt Trial, a global Phase 3 trial that aims to demonstrate the metabolic benefits of TransCon hGH in adults and with the primary objective to evaluate change in trunk fat percentage.

In December 2023, the company announced positive topline results from foresiGHt, a Phase 3 randomized, parallel-arm, placebo-controlled (double-blind) and active-controlled (open-label) trial to compare the efficacy and safety of TransCon hGH with placebo and daily hGH in adults with GHD.

TransCon hGH was generally safe and well tolerated, with no discontinuations related to study drug and with comparable safety and tolerability to daily hGH.

Other Development Plans

In June 2022, the company initiated the Phase 2 New InsiGHTS Trial in the U.S. to evaluate TransCon hGH in Turner syndrome. In this trial, the company is evaluating higher doses of TransCon hGH and daily hGH for Turner syndrome compared to doses for pediatric or adult GHD. Topline results from New InsiGHTS are expected in the fourth quarter of 2024. In addition, the company is considering other potential indications for TransCon hGH where a long-acting hGH therapy may offer benefits to patients with rare growth disorders, including in combination with the company’s TransCon CNP product candidate in achondroplasia.

TransCon PTH

The company is also aware of several academic groups and companies working on making longer-acting agonists of the PTH receptor (‘PTH1R’). In addition, other companies and groups are developing or commercializing therapies for hypoparathyroidism, including Calcilytix (a BridgeBio company), Entera Bio, Extend Biosciences, Massachusetts General Hospital, Amolyt Pharma, and MBX Biosciences.

Teriparatide, PTH (1-34), approved since 2002 for the treatment of osteoporosis, has sometimes been used for the treatment of hypoparathyroidism using multiple daily injections, despite not being approved for this indication. Clinical research conducted by the National Institutes of Health (‘NIH’) in subjects receiving continuous exposure to PTH (1-34), administered by an infusion pump, demonstrated simultaneous normalization of sCa and urinary calcium, as well as normalization of bone turnover.

Solution: TransCon PTH

TransCon PTH (palopegteriparatide) is an investigational prodrug of PTH (1-34) that is designed to be dosed once-daily to achieve and maintain a steady concentration of PTH in the bloodstream within the normal range, at levels similar to those observed in healthy individuals. TransCon PTH is designed to provide PTH in the physiological range for 24 hours per day, thereby more fully addressing all aspects of the disease, including normalizing serum and urinary calcium and serum phosphate levels.

With once-daily dosing, this substantial half-life extension of PTH could more closely reflect the physiological levels of PTH observed in healthy individuals, thereby maintaining blood calcium levels and normalizing urinary calcium excretion. By providing steady levels of PTH in the physiological range, TransCon PTH can address the fundamental limitations of PTH therapies with short half-life molecules and become a highly differentiated therapy for hypoparathyroidism.

In November 2023, TransCon PTH received regulatory approval in the EU and other territories and will be marketed in the EU as YORVIPATH, a parathyroid hormone (PTH) replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism.

In January 2024, the company announced that YORVIPATH is commercially available in Germany and Austria.

Clinical Development of TransCon PTH for Adult Hypoparathyroidism

The company’s ongoing Phase 3 PaTHway Trial, Phase 3 PaTHway Japan Trial, and Phase 2 PaTH Forward Trial are evaluating TransCon PTH in adult patients with hypoparathyroidism. Following the primary outcome period, all three trials continue in the open-label extension portion to collect long-term data.

In December 2023, the company announced that the FDA accepted for review its resubmitted New Drug Application (‘NDA’) for TransCon PTH (palopegteriparatide) for the treatment of adult patients with hypoparathyroidism. The agency considered the resubmission a complete, class 2 response and set a PDUFA goal date of May 14, 2024. In the U.S., TransCon PTH (palopegteriparatide) is an investigational prodrug of parathyroid hormone (PTH [1-34]) for adult patients with hypoparathyroidism. The resubmission followed the Type A meeting held with the FDA in late August, held after the FDA's issuance of a complete response letter (‘CRL’) in May 2023 for the TransCon PTH (palopegteriparatide) NDA for the treatment of adults with hypoparathyroidism. In the CRL, the FDA cited concerns related to the manufacturing control strategy for variability of delivered dose in the TransCon PTH drug/device combination product. The FDA did not express concern in the CRL about the clinical data submitted as part of the NDA package and no new preclinical studies, or Phase 3 clinical trials to evaluate safety or efficacy, were requested in the letter.

In September 2023, the company announced new post hoc analysis showing adults with hypoparathyroidism treated with TransCon PTH demonstrated substantial improvement in estimated glomerular filtration rate (‘eGFR’), suggesting improved kidney function.

In June 2023, the company announced one-year (Week 52) data from the open-label extension (‘OLE’) portion of the Phase 3 PaTHway Trial of TransCon PTH in adults with hypoparathyroidism. PaTHway is a Phase 3 trial of TransCon PTH with a placebo-controlled 26-week blinded portion and a 156-week OLE portion, designed to evaluate the long-term efficacy and safety of TransCon PTH as a potential hormone therapy for adult patients diagnosed with hypoparathyroidism. Of the 82 study participants dosed, 79 completed blinded treatment and entered the OLE, and 78 (59 TransCon PTH/TransCon PTH, 19 placebo/TransCon PTH) completed Week 52. The data showed that treatment with TransCon PTH resulted in sustained improvements through Week 52, as well as safety and tolerability similar to that reported for the initial 26-week blinded portion of the trial. As of December 31, 2023, 75 out of 79 patients continue in the OLE and have exceeded two years of follow-up in the PaTHway Trial.

In June 2023, the company started enrollment for a Compassionate Use Program (‘CUP’) in Germany for TransCon PTH (palopegteriparatide). The CUP was approved by Germany’s Federal Institute for Drugs & Medical Devices (Bundesinstitut für Arzneimittel & Medizinprodukte). Through the CUP, treating physicians can request TransCon PTH (palopegteriparatide) for eligible adult patients with hypoparathyroidism whose clinical condition, in the opinion of the treating physician, requires PTH treatment with palopegteriparatide, and who cannot be adequately treated with approved products or participate in a palopegteriparatide clinical trial. Following the German commercial launch of YORVIPATH in January 2024, the CUP will draw to a close.

On January 8, 2023, the company announced topline data from PaTHway Japan, a single-arm Phase 3 trial to evaluate the safety, tolerability, and efficacy of TransCon PTH in adults with hypoparathyroidism. The study achieved its primary objective, with topline results consistent with the company’s trials in North America and the EU. Twelve out of thirteen patients met the primary composite endpoint, which was defined as serum calcium levels in the normal range (8.3–10.6 mg/dL) and independence from conventional therapy (active vitamin D and >600 mg/day of calcium supplements). In this trial, TransCon PTH was generally well-tolerated, with no discontinuations related to study drug. As of December 31, 2023, 12 patients continue in the ongoing 3-year extension portion of the PaTHway Japan Trial.

In December 2022, the FDA allowed the company to initiate a U.S. expanded access program (‘EAP’) for TransCon PTH for eligible adult patients with hypoparathyroidism with prior PTH treatment experience. This EAP is open for enrollment, allowing the U.S. physicians to request access to investigational TransCon PTH for their eligible patients.

In September 2022, the company announced new Week 110 data from the Phase 2 PaTH Forward Trial showing that long-term therapy with TransCon PTH provided a durable response in adult patients with hypoparathyroidism, as evidenced by maintenance of normal mean serum calcium levels and 93% of patients achieving independence from conventional therapy with active vitamin D and oral calcium. As of December 31, 2023, 57 out of the 59 patients continued in the OLE portion of the trial, where they receive an individualized maintenance dose of TransCon PTH. In addition, all 57 subjects have exceeded three years of follow-up in the PaTH Forward Trial. Two patients withdrew from the trial for reasons unrelated to safety or efficacy of the study drug.

In March 2022, the company announced that top-line data from the randomized, double-blind, placebo-controlled portion of the Phase 3 PaTHway Trial of TransCon PTH in adults with hypoparathyroidism demonstrated statistically significant higher proportion of participants treated with TransCon PTH achieved the primary composite endpoint compared to placebo.

In April 2020, the company announced top-line data from the four-week fixed dose, double-blinded portion of PaTH Forward, a global Phase 2 trial evaluating the safety, tolerability and efficacy of TransCon PTH in adult subjects with hypoparathyroidism. A total of 59 subjects were randomized in a blinded manner to receive fixed doses of TransCon PTH at 15, 18 or 21 µg/day or placebo for four weeks using a ready-to-use prefilled pen injector planned for commercial presentation. All doses of TransCon PTH were well-tolerated, and no serious or severe treatment-related adverse events (‘TEAEs’), were observed at any point. No treatment-emergent adverse events led to discontinuation of study drug, and the overall incidence of TEAEs was comparable between TransCon PTH and placebo. Additionally, there were no drop-outs during the four-week fixed dose period.

In June 2018, the company was granted Orphan Drug Designation (‘ODD’) by the FDA, for TransCon PTH for the treatment of hypoparathyroidism. In October 2020, the company was granted Orphan designation (‘OD’) by the EC for TransCon PTH for the treatment of hypoparathyroidism. In July 2021, the Ministry of Health, Labour and Welfare granted ODD to TransCon PTH for the treatment of hypoparathyroidism.

TransCon CNP

In November 2021, BioMarin Pharmaceutical Inc.’s VOXZOGO (vosoritide) was approved by the FDA and is indicated to increase linear growth in pediatric patients with achondroplasia with open epiphyses. Other companies that are developing therapies for achondroplasia include QED Therapeutics (a BridgeBio company), Sanofi, Ribomic, Tyra Biosciences, and ProLynx.

Solution: TransCon CNP

TransCon CNP (navepegritide) is an investigational prodrug of CNP administered once weekly and designed to provide sustained release of active CNP supporting continuous exposure for the treatment of achondroplasia. TransCon CNP is designed to provide effective shielding of CNP from neutral endopeptidase degradation in subcutaneous tissue and the blood compartment, minimize binding of CNP to the NPR-C receptor to decrease clearance, reduce binding of CNP to the NPR-B receptor in the cardiovascular system to avoid hypotension, and release unmodified CNP, which is small enough in size to allow effective penetration into growth plates. Shorter-acting CNP and CNP analogs in development have resulted in high Cmax levels that may cause adverse cardiovascular events. The therapeutically sustained release of TransCon CNP offers advantages that may mitigate this issue, leading to more constant CNP exposure at lower Cmax to correlate with better therapeutic outcomes.

Clinical Development of TransCon CNP for Achondroplasia

The company’s ongoing pivotal ApproaCH Trial, ACcomplisH trial, and the company’s long-term extension trial AttaCH, are evaluating the safety and efficacy of TransCon CNP in children (aged 2 to eleven years) with achondroplasia.

In December 2023, the company announced new analyses demonstrating benefits beyond linear growth from the blinded and ongoing OLE portions of ACcomplisH, a Phase 2 randomized, double-blind, placebo-controlled, dose-escalation trial of TransCon CNP in children ages 2-10 years with achondroplasia. In the trial, all 57 patients have now completed one year of treatment with TransCon CNP at 100 µg/kg/week, the dose agreed with regulatory agencies for the active arm in the company’s pivotal ApproaCH Trial.

The company analyzed available data for patients who only received TransCon CNP at the 100 µg/kg/week dose in either blinded or OLE part and were treated for one year (n=19), compared to those administered placebo for one year (n=15). Results showed that these TransCon CNP-treated patients (data available for 9-16 patients) showed significant improvements in health-related quality of life and disease impacts compared to those receiving placebo (data available for 5-13 patients).

During the fourth quarter of 2023, the company filed a Clinical Trial Application for COACH, a Phase 2 open-label single-arm trial evaluating TransCon CNP and TransCon hGH in children with achondroplasia (age 2 to 11 years). The primary objective is to evaluate the treatment effect on linear growth and safety. Secondary objectives are to evaluate treatment effect on quality of life, radiological endpoints, physical functioning, and body composition. The trial plans to enroll approximately 18 patients (treatment naïve, n=18; prior treatment with TransCon CNP (100 mg/kg/week) for at least 1 year, n=6).

During the third quarter of 2023, the company filed an IND amendment with the FDA to initiate reACHin, a Phase 2, multicenter, double-blind, randomized, placebo-controlled trial, designed to evaluate the safety, tolerability, and efficacy of 100 µg CNP/kg of TransCon CNP once-weekly for 52 weeks in infants with achondroplasia, aged 0 to < 2 years at the time of randomization.

In September 2023, the company announced the completion of enrollment in ApproaCH with a total of 84 subjects randomized. The U.S. and EU regulatory agencies have endorsed ApproaCH, a global randomized, double-blind, placebo-controlled trial in children ages 2–11 years with achondroplasia, as a pivotal Phase 3 trial. The primary endpoint of the trial is annualized growth velocity at 52 weeks with additional endpoints analyzing achondroplasia-related co-morbidities and quality of life. Topline results from the ApproaCH trial are expected in the fourth quarter 2024.

In November 2022, the company announced topline results from ACcomplisH, a Phase 2 randomized, double-blind, placebo-controlled, dose-escalation trial evaluating the safety and efficacy of once-weekly TransCon CNP compared to placebo in children with achondroplasia aged two to ten years old.

In 2019, the company initiated the ACHieve Study, a five-year, multi-center natural history study designed to gain insight into the experiences of pediatric patients with achondroplasia. ACHieve is designed to evaluate growth velocity, body proportionality, and comorbidities over time in children with achondroplasia up to eight years old. No study medication will be administered in the ACHieve Study.

In February 2019, the company was granted ODD by the FDA for TransCon CNP for the treatment of achondroplasia. In July 2020, the company received OD from the EC for TransCon CNP for the treatment of achondroplasia.

TransCon Product Candidates—Oncology

Solution: TransCon Technologies for Oncology

The company is investigating two clinical-stage product candidates designed to activate the patient’s own immune system to eradicate malignant cells. The company’s approach, if successfully developed, has the potential to improve the efficacy of systemically administered, clinically validated therapies while limiting adverse effects.

Similarly, with the potential to achieve sustained local release at predictable levels, TransCon hydrogel product candidates may allow for improved efficacy and reduced dosing frequency of intratumorally administered therapies, potentially enabling treatments of multiple tumor types, including those that cannot be easily accessed for frequent injection.

Development of TransCon Product Candidates in Oncology

The company’s TransCon product candidates in oncology are designed to provide sustained systemic or intratumoral administration, which could provide potent and durable anti-tumor efficacy. The company’s nonclinical studies have shown sustained activation of cytotoxic immune cells that resulted in robust anti-tumor responses by TransCon product candidates using infrequent administration.

Two of the company’s oncology product candidates, TransCon TLR7/8 Agonist and TransCon IL-2 b/g, are now in clinical development. In addition, a combination of TransCon TLR7/8 Agonist and TransCon IL-2 b/g may have the potential to produce greater anti-tumor activity than either candidate alone.

TransCon TLR7/8 Agonist for Sustained Localized Release

TransCon TLR7/8 Agonist is an investigational long-acting prodrug, designed for sustained intratumoral release of resiquimod, a small molecule agonist of TLR 7 and 8. It is designed to provide sustained and potent activation of the innate immune system in the tumor and tumor draining lymph node for weeks following a single intratumoral injection and to have a low risk of systemic toxicity. The transcendIT-101 Trial, a Phase 1/2 clinical trial to evaluate the safety and efficacy of TransCon TLR7/8 Agonist in locally advanced or metastatic solid tumors, alone or in combination with pembrolizumab, has completed dose escalation and is enrolling patients in four indication-specific cohorts where increased TLR7/8 activity has potential to improve innate and adaptive immune activation and host defense against cancers: head and neck squamous cell carcinoma (HNSCC), HPV-associated cancers, melanoma, and cutaneous squamous cell carcinoma (cSCC). Initial data from these cohorts are expected by the end of 2024.

In May 2023, the company announced additional follow-up from the transcendIT-101 Trial indicating further clinical activity in patients receiving TransCon TLR7/8 Agonist as monotherapy or in combination with pembrolizumab. Enrollment continues in the Phase 2 portion of transcendIT-101 at the recommended Phase 2 dose (‘RP2D’).

In November 2022, the company announced new data (cutoff date of September 21, 2022) from the dose-escalation portion of transcendIT-101. All 23 of the patients enrolled in the dose escalation portion of the trial had advanced or metastatic solid tumors that had progressed on prior treatments, 9 in the monotherapy cohort (intratumoral TransCon TLR7/8 Agonist alone) and 14 in the combination therapy cohort (intratumoral TransCon TLR7/8 Agonist plus the check-point inhibitor pembrolizumab). Two dose levels were evaluated: 0.3 mg/lesion and 0.5 mg/lesion. The RP2D was declared at 0.5 mg/lesion for up to two lesions, which is being evaluated in four indication specific cohorts.

TransCon IL-2 b/g for Sustained Systemic Release

TransCon IL-2 b/g is an investigational long-acting prodrug designed to improve cancer immunotherapy through sustained release of an IL-2 variant that selectively activates IL-2 b/g, with minimal binding to IL-2Ra. The IL-Believe Trial, a Phase 1/2 clinical trial to evaluate the safety and efficacy of TransCon IL-2 b/g in locally advanced or metastatic solid tumors, alone or in combination with pembrolizumab or standard of care chemotherapy, has completed dose escalation and is enrolling patients in multiple indication-specific dose expansion cohorts, including platinum-resistant ovarian cancer (PROC), cervical cancer, melanoma, non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC) at the RP2D. Initial data from these cohorts are expected by the end of 2024.

During the fourth quarter of 2023, the first patient was dosed with the combination of TransCon IL-2 b/g and TransCon TLR7/8 Agonist in the post PD-1 melanoma dose expansion cohort in the IL-Believe Trial.

In October 2023, the company announced new and updated data from the ongoing IL-Believe Trial. Forty-six patients were enrolled into dose escalation cohorts: 25 to monotherapy and 21 to combination therapy. As of the August 15, 2023 data cutoff, anti-tumor clinical responses were observed with TransCon IL-2 b/g monotherapy (colorectal cancer with confirmed partial response (‘PR’)) or in combination with pembrolizumab (small cell lung cancer, one with confirmed PR and one ongoing with unconfirmed complete response) in heavily pre-treated patients who previously progressed on checkpoint inhibitors. TransCon IL-2 b/g every three weeks was generally well-tolerated, with no meaningful effect on Tregs and eosinophils.

In September 2023, the company announced the completion of Phase 1 dose escalation in combination with pembrolizumab of the IL-Believe Trial with a total of 21 patients enrolled and RP2D determined at 120 µg/kg IV every three weeks. Twenty-one patients were enrolled.

In May 2023, the company announced the completion of the Phase 1 monotherapy dose escalation of the IL-Believe Trial with RP2D determined at 120 µg/kg IV every three weeks with 25 heavily pre-treated patients enrolled and a median of four prior lines of systemic therapies.

Other Development Plans

To further evaluate safety and anti-tumor efficacy of TransCon TLR7/8 Agonist and TransCon IL-2 b/g, the company is also evaluating these product candidates as neoadjuvant therapy in the ongoing randomized Phase 2 BelieveIT-201 trial in resectable locally advanced head and neck squamous cell carcinoma.

Strategic Collaborations

In November 2023, the company entered into an exclusive license agreement with Teijin Limited for the further development and commercialization of TransCon hGH, TransCon PTH, and TransCon CNP for endocrinology rare disease in Japan.

Strategic Investments

VISEN Pharmaceuticals

In November 2018, the company announced the formation of VISEN, a company established to develop and commercialize the company’s endocrinology rare disease therapies in the People’s Republic of China, Hong Kong, Macau, and Taiwan (‘Greater China’). In connection with the formation of VISEN, the company granted VISEN exclusive rights to develop and commercialize certain product candidates based on the company’s proprietary TransCon technologies, including TransCon hGH, TransCon PTH and TransCon CNP, in Greater China for use in all human indications, subject to certain exceptions.

In November 2023, VISEN announced topline results from the Phase 2 ACcomplisH China Trial in children with achondroplasia aged 2 to 10 years. The trial met its primary objectives, demonstrating that TransCon CNP at 100 µg/kg/week was superior to placebo on the primary efficacy endpoint of AGV at 52 weeks (p=0.018).

In November 2022, VISEN announced data from its pivotal Phase 3 study of TransCon hGH in children with GHD in China. The trial achieved its primary endpoint; patients treated with TransCon hGH demonstrated greater annualized height velocity at 52-weeks (p=0.0010) compared to patients treated with daily growth hormone with comparable safety and tolerability to daily growth hormone.

In June 2022, VISEN announced it had completed enrollment of the Phase 3 PaTHway China Trial of TransCon PTH.

The purpose of the company’s investment in VISEN is to support the company’s strategy to extend its endocrinology rare disease portfolio globally and establish a presence in China in partnership with collaborators who have significant experience and knowledge of the biopharmaceutical opportunity in China.

The company entered into a clinical supply agreement with VISEN in 2018 to provide product supply for use in conducting clinical trials in Greater China. Additionally, during 2023, the company entered into a commercial supply agreement governing commercial supply of licensed product (TransCon hGH) to VISEN on the terms and conditions set forth in the Rights Agreements.

Eyconis

In January 2024, the company announced the formation and launch with Frazier Life Sciences of Eyconis, Inc., a separate company created to develop, manufacture, and commercialize TransCon ophthalmology assets globally.

The company has granted Eyconis exclusive rights to develop and commercialize TransCon ophthalmology products globally and received an equity position in the newly formed company. In addition, the company will be eligible to receive development, regulatory, and sales milestone payments, plus single digit royalties on global net sales of commercialized products, if any. Eyconis will initially be based in Redwood City, California, and certain employees of Ascendis are expected to join the newly formed company.

Manufacturing

The manufacturing facilities for the company’s products must be in compliance with cGMP (current good manufacturing practice) requirements, and for device and device components, the Quality System Regulation (‘QSR’) requirements, before any product is approved.

NOF Manufacturing and Supply Agreement Related to TransCon hGH

On December 21, 2017, the company entered into a multi-year Manufacturing and Supply Agreement (the ‘NOF Agreement’) with NOF Corporation (‘NOF’). Under the NOF Agreement, NOF has agreed to manufacture and supply the mPEG Linker (the ‘NOF hGH Product’) for the company’s TransCon hGH product candidate. The company has agreed to purchase certain quantities of NOF hGH Product.

The NOF Agreement is effective as of December 21, 2017. The initial term of the NOF Agreement terminates on December 31, 2025 unless earlier terminated.

NOF Manufacturing and Supply Agreement Related to TransCon PTH

On August 31, 2020, the company entered into a multi-year Manufacturing and Supply Agreement (the ‘NOF PTH Agreement’) with NOF. Under the NOF PTH Agreement, NOF has agreed to manufacture and supply the PEG maleimide (the ‘NOF PTH Product’) for the company’s TransCon PTH product candidate. The company has agreed to purchase certain quantities of NOF PTH Product. The company may purchase NOF PTH Product from other manufacturers and are not obligated to purchase NOF PTH Product from NOF, other than certain quantities that have been forecasted by the company in accordance with a mandatory rolling forecast that the company must deliver to NOF from time to time.

The NOF PTH Agreement is effective as of August 31, 2020. The initial term of the NOF PTH Agreement terminates on December 31, 2027 unless earlier terminated.

Carbogen Manufacturing and Supply Agreement Related to TransCon hGH

On October 26, 2018, the company entered into a multi-year Manufacturing and Supply Agreement (the ‘Carbogen Agreement’) with Carbogen Amcis AG (‘Carbogen’). Under the Carbogen Agreement, Carbogen has agreed to manufacture and supply Linker A (the ‘Carbogen Product’) for the company’s TransCon hGH product candidate. The company may purchase Linker A from other manufacturers and are not obligated to purchase Carbogen Product from Carbogen, other than certain quantities that have been forecasted by the company in accordance with a mandatory rolling forecast that the company must deliver to Carbogen from time to time.

The Carbogen Agreement is effective as of October 26, 2018. The initial term of the Carbogen Agreement expires five years after the first commercial launch of the company’s TransCon hGH product candidate (the ‘Carbogen Initial Term’) unless earlier terminated. After the expiration of the Carbogen Initial Term of the Carbogen Agreement, the Carbogen Agreement continues until it is terminated.

Carbogen Manufacturing and Supply Agreement Related to TransCon PTH

On May 27, 2021, the company entered into a multi-year Manufacturing and Supply Agreement (the ‘Carbogen PTH Agreement’) with Carbogen. Under the Carbogen PTH Agreement, Carbogen has agreed to manufacture and supply Linker F (the ‘Carbogen PTH Product’) for the company’s TransCon PTH product candidate. The company may purchase Carbogen PTH Product from other manufacturers and are not obligated to purchase Carbogen PTH Product from Carbogen, other than certain quantities that have been forecasted by the company in accordance with a mandatory rolling forecast that the company must deliver to Carbogen from time to time.

The Carbogen PTH Agreement is effective as of May 27, 2021. The initial term of the Carbogen PTH Agreement expires five years after the first commercial launch of the company’s TransCon PTH product candidate (the ‘Carbogen PTH Initial Term’) unless earlier terminated. After the expiration of the Carbogen PTH Initial Term of the Carbogen PTH Agreement, the Carbogen PTH Agreement continues until it is terminated.

Phillips Medisize (formerly B&O Medicom and Medicom Innovation Partner)

On January 12, 2017, the company entered into a multi-year Manufacturing and Supply Agreement (the ‘Medicom Agreement’) with Medicom Innovation Partner (‘Medicom’). Under the Medicom Agreement, Medicom has agreed to exclusively manufacture and supply the auto injector injection device (the ‘Medicom Product’) for the company’s TransCon hGH product candidate. The company is obligated to purchase certain quantities that have been forecasted by the company in accordance with a mandatory rolling forecast that the company must deliver to Medicom from time to time.

The Medicom Agreement is effective as of January 12, 2017. The term of the Medicom Agreement terminates on June 30, 2025 (‘Medicom Initial Term’) unless earlier terminated or unless extended unilaterally by the company, with notice of extension to be given no later than June 30, 2024, by five years until June 30, 2030 (‘Extended Term’) after which date it shall continue indefinitely unless terminated.

Vetter Pharma International GmbH

On December 14, 2018, the company entered into a multi-year Supply Agreement (the ‘Vetter Agreement’) with Vetter Pharma International (‘Vetter’). Under the Vetter Agreement, Vetter has agreed to manufacture and fill-and-finish drug product in dual-chamber cartridges (the ‘Ascendis Product’) for the company’s TransCon hGH product candidate. Vetter has agreed to supply in accordance with a long-term forecast in addition to a rolling forecast with a binding part that the company must deliver to Vetter from time to time.

The Vetter Agreement is effective as of January 1, 2019. The term of the Vetter Agreement expires on the five-year anniversary of the date of first regulatory approval of the TransCon hGH product (the ‘Initial Term’) after which term it shall be automatically renewed for subsequent two-year terms unless terminated.

Lonza Tech Transfer and Manufacturing Agreement

On December 12, 2019, the company entered into a multi-year commercial supply agreement (the ‘Lonza Agreement’) with Lonza Ltd (‘Lonza’). Under the Lonza Agreement, Lonza has agreed to manufacture and supply drug substance for the company’s TransCon hGH product candidate (the ‘TransCon hGH Drug Substance’). Starting in 2023, the company is obligated to purchase a certain minimum annual quantity of TransCon hGH Drug Substance from Lonza. The company may also purchase TransCon hGH Drug Substance from other manufacturers.

The Lonza Agreement secures the company a certain capacity of TransCon hGH Drug Substance per year.

The Lonza Agreement is effective as of December 12, 2019. The initial term of the Lonza Agreement expires seven years after first approval of a drug product manufactured using the TransCon hGH Drug Substance (the ‘Lonza Initial Term’) unless earlier terminated.

Sharp Corporation Packaging and Supply Agreement

On December 1, 2019, the company entered into a multi-year packaging agreement (the ‘Sharp Agreement’) with Sharp Corporation (‘Sharp’). Under the Sharp Agreement, Sharp will package, assemble, and label TransCon hGH for commercial use in certain territories, including the United States and the EU. The company is non-exclusive to Sharp and may engage other manufacturers to package, assemble, and label TransCon hGH but the company is obligated to meet certain minimum spend requirements for TransCon hGH during the first 12-month period after first shipment of TransCon hGH for commercial sale after regulatory approval thereof.

The Sharp Agreement is effective as of December 1, 2019. The initial term of the Sharp Agreement expires on December 31, 2025 and will be automatically extended for additional two-year periods unless earlier terminated.

Bachem Manufacturing and Supply Agreement

On December 27, 2020, the company entered into a multi-year Manufacturing and Supply Agreement (the ‘Bachem Agreement’) with Bachem AG (‘Bachem’). Under the Bachem Agreement, Bachem has agreed to manufacture and supply PTH drug substance (the ‘Bachem Product’) for the company’s TransCon PTH product candidate. The company may purchase Bachem Product from other manufacturers and are not obligated to purchase Bachem Product from Bachem, other than certain quantities that have been forecasted by the company in accordance with a mandatory rolling forecast that the company must deliver to Bachem from time to time.

The Bachem Agreement is effective as of December 27, 2020. The initial term of the Bachem Agreement expires on December 31, 2027 (the ‘Bachem Initial Term’) unless earlier terminated. After the expiration of the Bachem Initial Term, provided that market approval is received prior to expiration of the Bachem Initial Term, the Bachem Agreement continues until it is terminated. The

Intellectual Property

As of December 31, 2023, the company owned a total of 93 patent families, of which 17 were in their priority year or international phase and the company owned several granted patents in the United States (51), Europe (31), Australia (41), Brazil (8), Canada (25), China (16), Israel (13), Indonesia (3), India (5), Korea (12), Malaysia (9), New Zealand (9), Japan (38), Mexico (14), Singapore (11), Russia (16), the United Arab Emirates (1) and South Africa (17); and had approximately 560 pending national/regional applications in a total of 26 jurisdictions (excluding the member states of the European Patent Convention in which the company’s European patents were validated, Hong Kong, to which certain Europe and China patents are extended, and Macao, to which certain China patents are extended).

TransCon hGH

The company’s patent portfolio related to TransCon hGH includes eight patent families relating to different aspects of TransCon hGH and an additional ten patent families covering various aspects of the auto-injector device for the administration of TransCon hGH. The first of these patent families is a composition of matter patent family directed to the particular stoichiometry of TransCon hGH and a related TransCon carrier. As of December 31, 2023, this patent family included patents granted in Europe and the United States. The company expects any patents granted in this patent family to expire in October 2024, absent any patent term adjustments or extensions.

The second of these patent families is a composition of matter patent family directed to a TransCon linker used in TransCon hGH. As of December 31, 2023, this patent family included patents granted in the United States, Europe, Australia, Brazil, Canada, Japan and Mexico and included a patent application in the United States. The company expects any patents granted in this patent family to expire in March 2025, absent any patent term adjustments or extensions.

The third of these patent families is a composition of matter patent family directed to a broad class of TransCon hGH lead candidate structures. As of December 31, 2023, this patent family included patents granted in the United States, Europe, Australia, Brazil, Canada, China, Israel, India, Japan, Mexico, Russia and South Africa and included patent applications in Europe, the United States and Brazil. The company expects any patents granted in this patent family to expire in April 2029, absent any patent term adjustments or extensions.

The fourth of these patent families is a composition of matter patent family directed to specific dry pharmaceutical compositions comprising TransCon hGH. As of December 31, 2023, this patent family included patents granted in the United States, Europe, Australia, Brazil, Canada, India, Israel, Mexico, Singapore and South Africa and included a patent application in the United States. The company expects any patents granted in this patent family to expire in December 2030, absent any patent term adjustments or extensions.

The fifth of these patent families is a composition of matter patent family directed to a broad class of TransCon hGH lead candidate structures. As of December 31, 2023, this patent family included patents granted in the United States, Australia, Europe, Japan, South Korea, Mexico, New Zealand, Russia, Singapore and South Africa and patent applications in the United States, Europe, Australia, Brazil, Canada, Israel, Japan, South Korea, Mexico, New Zealand, Russia and Singapore. The company expects any patents granted in this patent family to expire in November 2035, absent any patent term adjustments or extensions. One EP patent in this family was also used as a basis for requesting a supplementary protection certificate (‘SPC’) for SKYTROFA in Austria, Belgium, Bulgaria, Cyprus, the Czech Republic, Germany, Denmark, Estonia, Spain, Finland, France, Great Britain, Greece, Croatia, Hungary, Ireland, Iceland, Italy, Lithuania, Luxemburg, Latvia, Malta, The Netherlands, Norway, Poland, Portugal, Romania, Sweden, Slovenia and Slovakia. An SPC was already granted in Cyprus, the Czech Republic, Denmark, Spain, Finland, France, Greece, Hungary, Italy, Latvia, Malta, The Netherlands, Norway, Portugal, Sweden, Slovenia and Slovakia, with an expiration date of January 16, January 17 or January 18, 2037, depending on the country.

The sixth of these patent families is directed to a particular dosage regimen for long-acting growth hormone formulations. As of December 31, 2023, this patent family included a granted patent in Europe and patent applications in the United States and in Europe. The company expects any patents granted in this patent family to expire in November 2035, absent any patent term adjustments or extensions.

The seventh of these patent families is directed to potential superior efficacy achieved with TransCon hGH treatment. As of December 31, 2023, this patent family included patent applications in the United States, Europe, Australia, Canada, China, Israel, Japan, Mexico, and Singapore. The company expects any patents granted in this family to expire in March 2040, absent any patent term adjustments or extensions.

The eighth of these patent families is directed to the use of TransCon hGH in the treatment of an inflammation-induced disease, in particular of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. As of December 31, 2023, this patent family included patent applications in the United States, Europe, Australia, Brazil, Canada, China, Indonesia, Israel, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore and South Africa. The company expects any patents granted in this family to expire in March 2042, absent any patent term adjustments or extensions.

Seven of the ten patent families covering the auto-injector device with a filing date of December 29, 2016, include patent applications in the United States, Europe, Australia, Canada, Japan and New Zealand and eight granted patents in the United States, three granted patents in Europe, nine granted patents in Australia, two granted patents in Canada, one granted patent in New Zealand and eleven granted patents in Japan as of December 31, 2023. The company expects any patents granted from these patent families to expire in December 2036, absent any patent term adjustments or extensions. As of December 31, 2023, the two patent families covering the auto-injector device with a filing date of May 23, 2018 and June 29, 2018, respectively, included patent applications in the United States, Europe, the United Arab Emirates, Australia, Brazil, Canada, China, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore and South Africa and one granted patent in the United States, two granted patents in Australia, two granted patents in China, two granted patents in Japan, two granted patents in South Korea, one granted patent in Malaysia, two granted patents in Russia, one granted patent in Indonesia and one granted patent in South Africa. The company expects any patents granted from these patent families to expire in March and June 2038, respectively, absent any patent term adjustments or extensions. The last patent family is in its international phase and also has one pending patent application in Taiwan. The company expects any patents granted from this patent family to expire in September 2042, absent any patent term adjustments or extensions.

In addition to the SPCs, three requests for a patent term extension (‘PTE’) for SKYTROFA were filed based on one granted U.S. patent from the third patent family and two granted patents from the fourth patent family, from which one will be selected for the PTE upon allowance. For three of the three requests a preliminary assessment that the patents would be eligible for extension was received from FDA.

TransCon PTH

The company’s patent portfolio related to TransCon PTH includes eleven patent families relating to different aspects of TransCon PTH. The first of these patent families is a composition of matter patent family directed to the TransCon linker used in TransCon PTH. As of December 31, 2023, this patent family included granted patents in the United States, Europe, the United Arab Emirates, Australia, Canada, China, Israel, Japan, Mexico, Russia and South Africa and included patent applications in Europe, the United States and Brazil. The company expects any patents granted in this family to expire in January 2029, absent any patent term adjustments or extensions.

The second of these patent families is a composition of matter patent family directed to a broad class of TransCon PTH candidate structures. As of December 31, 2023, this patent family included patent applications in the United States, Europe, Australia, Brazil, Canada, China, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore and Thailand; and granted patents in the United States, Australia, China, Israel, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore and South Africa. The company expects any patents granted in this patent family to expire in February 2037, absent any patent term adjustments or extensions.

The third and fourth of these patent families are method of treatment patent families directed to a particular dosage regimen. As of December 31, 2023, one of these patent families includes patent applications in the United States, Europe, Australia, Brazil, Canada, China, Israel, Indonesia, Japan, South Korea, Malaysia, New Zealand, Russia and Thailand; and granted patents in the United States, Europe, China, Israel, Japan, Mexico, New Zealand, Russia, Singapore and South Africa. The other one of these patent families includes patent applications in the United States, Europe, Australia, Canada, China and Japan; and a granted patent in Australia, China and Japan. The company expects any patents granted in this patent family to expire in September 2037, absent any patent term adjustments or extensions.

The fifth of these patent families is a composition of matter family directed to PTH compounds exhibiting a beneficial pharmacokinetic profile. As of December 31, 2023, this patent family includes patent applications in the United States, Europe, Australia, Brazil, Canada, China, Israel, Japan, South Korea, New Zealand, Russia and Singapore; and a granted patent in the United States, Europe, China, Japan, South Korea, Mexico, New Zealand, Russia, Singapore and South Africa. The company expects any patents granted in this patent family to expire in September 2037, absent any patent term adjustments or extensions.

The sixth patent family relates to a starting dose for treatment with reversible PTH conjugates. As of December 31, 2023, this patent family includes patent applications in the United States, Europe, Australia, Brazil, Canada, China, Indonesia, Israel, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore, Thailand and South Africa; and a granted patent in Russia. The company expects any patents granted from this patent family to expire in May 2039, absent any patent term adjustments or extensions.

The seventh patent family relates to a pharmaceutical composition comprising reversible PTH conjugates. As of December 31, 2023, this patent family includes patent applications in the United States, Europe, Australia, Brazil, Canada, China, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, the Philippines, Russia, Singapore, Taiwan, Thailand, Vietnam and South Africa. The company expects any patents granted from this patent family to expire in February 2040, absent any patent term adjustments or extensions.

The eighth and ninth patent families relate to a method of titrating hypoparathyroidism patients off of standard of care within four weeks from the beginning of daily treatment with a PTH compound and the treatment of the physical and mental well-being of hypoparathyroidism patients, respectively. As of December 31, 2023, the eighth family includes patent applications in the United States, Europe, Australia, Brazil, Canada, China, Indonesia, Israel, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore and South Africa. The ninth patent family includes patent applications in the United States, Europe, Australia, Canada, China, Israel, Japan, South Korea and Mexico. The company expects any patents granted from this patent family to expire in September 2041, absent any patent term adjustments or extensions.

The tenth patent family relates to a reduction in bone mineral density in patients having increased bone mineral density. As of December 31, 2023, this patent family was in Patent Cooperation Treaty phase. The company expects any patents granted from this patent family to expire in September 2042, absent any patent term adjustments or extensions.

The eleventh patent family covers treatment of hypoparathyroidism initially with a long-acting PTH compound, followed by treatment with an ultra-long-acting PTH compound. As of December 31, 2023, this patent family was in Patent Cooperation Treaty phase. The company expects any patents granted from this patent family to expire in September 2042, absent any patent term adjustments or extensions.

TransCon CNP

The company’s patent portfolio related to TransCon CNP includes thirteen patent families relating to different aspects of TransCon CNP. The first of these patent families is a composition of matter patent family directed to the particular stoichiometry of TransCon CNP and a related TransCon carrier. As of December 31, 2023, this patent family included patents granted in Europe and the United States; and a patent application in Europe. The company expects any patents granted in this patent family to expire in October 2024, absent any patent term adjustments or extensions.

The second of these patent families is a composition of matter patent family directed to the TransCon linker used in TransCon CNP. As of December 31, 2023, this patent family included granted patents in the United States, Europe, the United Arab Emirates, Australia, Canada, China, Israel, Japan, Mexico, Russia and South Africa; and included patent applications in Europe, the United States and Brazil. The company expects any patents granted in this family to expire in January 2029, absent any patent term adjustments or extensions.

The third of these patent families is a composition of matter patent family directed to a broad class of TransCon CNP candidate structures. As of December 31, 2023, this patent family included patent applications in the United States, Europe, Australia, Canada, Israel, India, Japan, Mexico, Malaysia, New Zealand, Russia, Singapore and Thailand; and a granted patent in China, South Korea, Malaysia, Russia, Singapore and South Africa. The company expects any patents granted in this patent family to expire in January 2036, absent any patent term adjustments or extensions.

The fourth to the ninth patent families are composition of matter patent families directed various CNP compounds having beneficial properties. As of December 31, 2023, the first one of these six patent families included patent applications in the United States, Europe, Japan, Mexico and New Zealand and granted patents in the United States, Australia, Canada, Japan and South Africa. As of December 31, 2023, the second one included patent applications in the United States, Europe, Australia and Japan and a granted patent in the United States, Europe, Australia, Canada, Japan, and South Africa. As of December 31, 2023, the third one included patent applications in the United States, Europe, Australia, Brazil, Canada, Indonesia, Israel, India, Japan, South Korea, and Singapore; and a granted patent in the United States, Australia, China, Israel, Japan, Mexico, Malaysia, New Zealand and South Africa. As of December 31, 2023, the fourth one included patent applications in the United States, Europe, Australia and Israel; and a granted patent in the United States, Australia, Canada and New Zealand. As of December 31, 2023, the fifth one included patent application in the United States, Europe, Australia, Brazil, China, Israel and Singapore; and a granted patent in the United States, Australia, Canada, China, Israel, New Zealand and South Korea. As of December 31, 2023, the sixth one included patent applications in the United States, Europe, Australia, Canada, Israel and New Zealand; and a granted patent in the United States and Australia. The company expects any patents granted in these patent families to expire in January 2037, absent any patent term adjustments or extensions.

The tenth patent family covers a combination therapy of TransCon CNP. As of December 31, 2023, this patent family includes patent applications in the United States, Europe, Australia, Brazil, Canada, Israel, South Korea, Singapore and Thailand; and a granted patent in the United States, Europe, Australia, China, Indonesia, Israel, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore and South Africa. The company expects any patents granted from this patent family to expire in September 2037, absent any patent term adjustments or extensions.

The eleventh patent family relates to a pharmaceutical composition comprising reversible CNP conjugates. As of December 31, 2023, this patent family includes patent applications in the United States, Europe, Australia, Brazil, Canada, China, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, the Philippines, Russia, Singapore, Taiwan, Thailand, Vietnam and South Africa; and a granted patent in China. The company expects any patents granted from this patent family to expire in February 2040, absent any patent term adjustments or extensions.

The twelfth patent family relates to a pharmacologically effective dose of TransCon CNP. As of December 31, 2023, this patent family was in Patent Cooperation Treaty phase. The company expects any patents granted from this patent family to expire in December 2042, absent any patent term adjustments or extensions. One of the priorities of this family was also claimed by a further Patent Cooperation Treaty application relating to improving muscle function. The company expects any patents granted from this branch of the family to expire in November 2043.

The thirteenth patent family relates to a liquid formulation of TransCon CNP. As of December 31, 2023, this patent family was in Patent Cooperation Treaty phase. The company expects any patents granted from this patent family to expire in May 2043, absent any patent term adjustment or extensions.

TransCon TLR7/8 Agonist

As of December 31, 2023, the company’s patent portfolio related to TransCon TLR7/8 Agonist included seven patent families. The first patent family relates to hydrogels, which are first synthesized and subsequently loaded with drug-linker conjugates. As of December 31, 2023, this patent family included granted patents in the United States and in Europe. The company expects any patents granted in these patent families to expire in July 2025, absent any patent term adjustments or extensions.

The second patent family relates to a specific class of PEG-based hydrogels. As of December 31, 2023, this patent family included granted patents in the United States, Europe, Australia, Brazil, Canada, China, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore and South Africa; and patent applications in the United States, Europe and Thailand. The company expects any patents granted in this patent family to expire in July 2030, absent any patent term adjustments or extensions.

The third patent family relates to a broad class of TransCon TLR7/8 Agonist candidate structures. As of December 31, 2023, this patent family included patent applications in the United States, Europe, Argentina, the United Arab Emirates, Australia, Brazil, Canada, China, Eurasia, Egypt, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand, Vietnam and South Africa. The fourth to sixth patent families relate to TransCon TLR7/8 Agonist compounds having beneficial properties. As of December 31, 2023, the fourth patent family included patent applications in the United States, Europe, Australia, Canada, Israel and Singapore. The fifth patent included as of December 31, 2023, patent applications in the United States, Europe, Australia, Brazil, Canada, China, Israel, Japan, South Korea, Mexico, Russia, Singapore and South Africa. As of December 31, 2023, the sixth patent family included patent applications in the United States, Europe, Australia, Canada, Israel and Singapore. The company expects any patents granted in all four of these patent families to expire in January 2040, absent any patent term adjustments or extensions.

The seventh patent family relates to a pharmaceutical dose of TransCon TLR7/8 Agonist. As of December 31, 2023, this application was in Patent Cooperation Treaty phase. The company expects any patents granted from this patent family to expire in December 2042, absent any patent term adjustments or extensions.

TransCon IL-2 b/g

As of December 31, 2023, the company’s patent portfolio related to TransCon IL-2 b/g includes four patent families. The first of these patent families is a composition of matter patent family directed to a TransCon linker used in TransCon IL-2 b/g. As of December 31, 2023, this patent family included patents granted in the United States, Europe, Australia, Brazil, Canada, Japan and Mexico; and included a patent application in the United States. The company expects any patents granted in this patent family to expire in March 2025, absent any patent term adjustments or extensions.

The second and third patent family are composition of matter patent families directed to a broad class of TransCon IL-2 b/g lead candidate structures. As of December 31, 2023, the second patent family included patent applications in the United States, Europe, Australia, Brazil, Canada, China, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Russia, Singapore, Thailand and South Africa. The company expects any patents granted in this patent family to expire in March 2039. As of December 31, 2023, the third patent family included patent applications in the United States, Europe, Argentina, the United Arab Emirates, Australia, Brazil, Canada, China, Eurasia, Egypt, Indonesia, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand, Vietnam and South Africa. The company expects any patents granted in this patent family to expire in June 2041, absent any patent term adjustments or extensions.

The fourth patent family relates to a pharmaceutical dose of TransCon IL-2 b/g. As of December 31, 2023, this patent family consists of three U.S. provisional applications. The company expects any patents granted in this patent family to expire in May 2044, absent any patent term adjustments or extension.

TransCon Technologies

The company’s patent portfolio also includes patents and patent applications generally relating to the company’s TransCon technologies, including TransCon linkers, TransCon carriers and certain soluble conjugates. The company owns an aggregate of 16 patent families relating to TransCon linkers, the material components of which are described above. The company owns an aggregate of 11 patent families relating to TransCon carriers, the material components of which are described above. Finally, the company owns a composition of matter patent family that is directed to soluble conjugates in which one drug molecule is connected to one TransCon carrier molecule.

Government Regulation and Product Approval

The Federal Food, Drug, and Cosmetic Act; the Public Health Service Act; and their implementing regulations set forth, among other things, requirements for the research, testing, development, manufacture, quality control, safety, effectiveness, approval, labeling, storage, record keeping, reporting, distribution, import, export, advertising and promotion of the company’s products.

As the company receives, collects, processes, uses and stores personal and confidential data, the company is subject to diverse laws and regulations relating to data privacy and security, such as data breach notification laws, health information privacy and security laws, and consumer protection laws in the United States and abroad, including the General Data Protection Regulation (GDPR) and the U.K. GDPR.

Research and Development Costs

The company’s research and development costs were €413.5 million for the year ended December 31, 2023.

History

Ascendis Pharma A/S was founded under the laws of the Kingdom of Denmark in 2006 as a private limited liability company (Anpartsselskab, or ApS) and then transformed into a public limited liability company (Aktieselskab, or A/S) in 2007. The company was incorporated in 2006.