VISEN Pharmaceuticals Receives IND Approval to Initiate Phase 2 Clinical Trial of TransCon ™ CNP in Achondroplasia (ACH) in China

VISEN Pharmaceuticals, a biotech company committed to the treatment of endocrine-related diseases, introducing the world's leading treatment methods and drugs into the China market and hoping to provide more Chinese patients quick access to the world's most advanced and reliable treatment solutions, announced that the China Center for Drug Evaluation (CDE) of National Medical Products Administration (NMPA) has approved the IND application to conduct a phase 2 clinical trial of TransCon TM C-Type Natriuretic Peptide (CNP) for patients with achondroplasia (ACH). The trial is ready to be launched in China as "the ACcomplisH China trial", in coordination with the ACcomplisH trial, an ongoing phase 2 global clinical trial of TransCon CNP being conducted globally outside of China by Ascendis Pharma.

TransCon CNP is an investigational once-weekly long-acting prodrug of CNP in development for the treatment of ACH in pediatric patients. It is designed to provide continuous CNP exposure which inhibits the effect of constitutive fibroblastgrowth factor receptor 3 (FGFR3) over-activation 24 hours a day, aiming to promote bone growth and ameliorate and prevent complications and comorbidities of ACH. TransCon CNP received Orphan Designation and Orphan Drug Designation (ODD) by the European Commission and the United States Food and Drug Administration (U.S. FDA), respectively.

ACH Poses Heavy Burden on Patients, their Families, and Society

ACH is a genetic disease and the most common form of dwarfism, caused by an autosomal dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3) that leads to an imbalance between the FGFR3 and CNP signaling pathways. Around 80 percent of individuals with ACH have parents with normal stature and have achondroplasia as the result of a de novo pathogenic variant[1] and may experience severe skeletal complications and comorbidities. According to available data, the global incidence of the disease is approximately 1 in 25,000[2] in the newborn, affecting about 250,000 people worldwide[3] . Affected individuals have rhizomelic shortening of the limbs, macrocephaly, and characteristic facial features with frontal bossing and midface retrusion. Hypo dystonia in infancy is typical, and patients typically reach an average height of only about 1.31m for males, 1.24m for females by adulthood[4]. ACH can also lead to a variety of serious complications, including foramen magnum stenosis, obstructive sleep apnea and chronic ear infections, resulting in poor quality of life and an increased risk of death.

Achondroplasia can be diagnosed by characteristic clinical and radiographic findings in most affected individuals[1]. In individuals in whom there is diagnostic uncertainty or who have atypical findings, identification of a heterozygous pathogenic variant in FGFR3 can establish the diagnosis[1]. There are currently no effective drugs approved for ACH[2]. Due to the lack of fundamental treatment options, the prevention and control for a variety of comorbidities often leads to high medical expenses, bringing a heavy burden to patients, their families, and the social insurance system. Additional difficulties in self-care, education, and employment, low income and other factors provide obstacles to patients' full integration into society, which further increases the burden of living, and in turn results in the unemployment, care burden on families and increase in social insurance expenditures. The situation underlines the urgent need to accelerate the research and development of new drugs targeting the pathogeny to alleviate the burden on patients, families, and society.

Phase 2 Clinical Trial of TransCon CNP Sets to Accelerate Research and Development

Preclinical and clinical data have shown that increased CNP can offset the effects of the FGFR3 mutation, thereby promoting bone growth[5]. However, the half-life of natural CNP in the human body is short, only 2-3 minutes[6], requiring continuous intravenous infusion, posing significant difficulties for clinical application.

Currently, TransCon CNP is the world's only long-acting CNP designed with the patented TransCon[7] "Transient Conjugation" technology platform, with a demonstrated effective CNP half-life of approximately 120 hours[8]. The results of animal experiments showed that TransCon CNP reversed the phenotype, restored growth, and supports potential to ameliorate some of the most disabling achondroplasia traits, including stenosis of the foramen magnum[9]. A phase 1 global trial of TransCon CNP conducted by Ascendis Pharma reproduced the pharmacokinetic profile and cardiovascular safety demonstrated in preclinical studies and demonstrated that TransCon CNP was generally well tolerated without serious adverse events (SAEs) reported nor anti-CNP antibodies detected[10] .

"The ACcomplisH China trial is an important part of the global clinical development plan, and its IND approval has come after thorough and repeated demonstration of its rationality and safety," said Dr. Jun Yang, CMO of VISEN Pharmaceuticals. "The trial will be a multi-center, randomized, placebo-controlled, phase 2 trial to evaluate the safety and efficacy in patients with ACH administered weekly via subcutaneous injection of TransCon CNP. The primary endpoint is to evaluate the safety of treatment and its effect on 12-month annualized height velocity (AHV). We look forward to accelerating the global research and development of this innovative drug as we continue to ensure patient safety and quality of the trials."

"Patient First" VISEN Pharmaceuticals Intends to Utilize China Clinical Data to Boost Global Research and Development                                                                                                                    

In recent years, China has placed a high premium on the management of rare diseases and has taken numerous measures to promote the prevention and treatment of rare diseases. Chapter 5, Article 60 of the Law of the People's Republic of China on the Promotion of Basic Medical and Health Care enacted this year calls for the state to establish a demand-oriented clinical drug evaluation and approval system, as well as support the development and production of clinical urgent drugs and drugs for the prevention and treatment of rare and major diseases, to meet the demands of disease prevention and treatment.

"Thanks to the support from the government and the tireless efforts of our many partners, the phase 2 clinical trial of TransCon CNP will be launched, in synchronization with the ACcomplisH Trial being conducted by Ascendis Pharma," said Pony Lu, CEO of VISEN Pharmaceuticals. "This will help more Chinese ACH patients gain access to a potentially effective treatment directly targeting the fundamental pathogenesis of ACH. In addition, China clinical data will serve as important support for accelerating the global research and development of this innovative drug, helping ACH patients around the world. VISEN Pharmaceuticals has always been dedicated to putting 'Patients First'. In the future, we will continue to actively join our partners to promote the awareness of the whole society of China's ACH patients, to accelerate the improvement of diagnosis and treatment of ACH in China, and to contribute to the early realization of 'Healthy China 2030'. "

About VISEN Pharmaceuticals

VISEN Pharmaceuticals is committed to the treatment of endocrine-related diseases, introducing the world's leading treatment methods and drugs into the China market and hoping to provide more Chinese patients quick access to the world's most advanced and reliable treatment solutions.

In 2018, VISEN Pharmaceuticals (VISEN) was formed by Ascendis Pharma A/S (Nasdaq: ASND) and an investor syndicate led by Vivo Capital (along with participation by Sofinnova Ventures), to develop and commercialize Ascendis Pharma's endocrinology rare therapies in Greater China, which includes mainland China, Hong Kong, S.A.R., China, Macau, S.A.R., China, and Taiwan, China.

About TransCon™ Technology

TransCon refers to "transient conjugation." The proprietary TransCon platform is an innovative technology designed to create new therapies that potentially optimize therapeutic effect, including efficacy, safety and dosing frequency.

TransCon molecules have three components: an unmodified 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 conditions (e.g., pH and temperature) initiate the release of the active, unmodified parent drug in a predictable manner. Because the parent drug is unmodified, its original mode of action may be maintained. TransCon technology is designed to be applied broadly to a protein, peptide or small molecule in multiple therapeutic areas, and to be used systemically or locally.

About Ascendis Pharma A/S

Ascendis Pharma is applying its innovative TransCon technologies to build a leading, fully integrated biopharmaceutical company focused on making a meaningful difference in patients' lives. Guided by its core values of patients, science and passion, the company utilizes its TransCon technologies to create new and potentially best-in-class therapies.

Ascendis Pharma currently has a pipeline of three independent endocrinology rare disease product candidates in clinical development and is advancing oncology as its second therapeutic area of focus. The company continues to expand into additional therapeutic areas to address unmet patient needs.

Ascendis is headquartered in Copenhagen, Denmark, with additional offices in Heidelberg and Berlin, Germany, and in Palo Alto and Redwood City, California.

[1] https://www.ncbi.nlm.nih.gov/books/NBK1152/

[2] Pauli RM. Orphanet J Rare Dis. 2019;14(1):1-49

[3] Waller DK, Correa A, Vo TM, Wang Y, Hobbs C, Langlois PH, et al. The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US. Am J Med Genet A 2008;146A: 2385–9

[4] Tachibana K, Suwa S, Nishiyama S, Matsuda I. Study on height in patients with achondroplasia by national survey. Shounika Sinryou 1997;60: 1363–9

[5] Horton WA, et al. Lancet. 2007;370(9582):162–172

[6] Vibeke Miller Breinholt, et al. TransCon CNP, a Sustained-Release C-Type Natriuretic Peptide Prodrug, a Potentially Safe and Efficacious New Therapeutic Modality for the Treatment of Comorbidities Associated with Fibroblast Growth Factor Receptor 3–Related Skeletal Dysplasias. J Pharmacol Exp Ther. 2019;370(3):459-471

[7] TransCon is a registered trademark of Ascendis Pharma A/S

[8] TransCon CNP: A Once Weekly Novel C type Natriuretic Peptide Therapy in Children with Achondroplasia, Sho Ota, PharmD Ascendis Pharma, A/S; ISDS CONFERENCE SEPTEMBER 2019, OSLO

[9] ENDO 2017 PR

[10] TransCon CNP: Preliminary Phase 1 Data November 28, 2018