Our path to value creation
Following the successful completion of a first-in-man study of X842, the next planned step is to initiate a phase II study in H2 2020. The primary purpose of this proof-of-concept trial is to gain further understanding of the safety profile and establish the efficacy of X842 in healing of grade C and D esophagitis. Following the completion of the phase II study, initiation of a phase III program in the same target population is slated for H2 2021/H1 2022.
Proven mode of action
Safety data on parent drug known1)
Linaprazan, the active metabolite of X842, was safe and well tolerated based on studies in ~2,500 subjects and standard pre-clinical studies needed for regulatory submission for market access (including two-year carcinogen studies in two species)
Cut-off 240 nmol/L = pH >4
Clear PK/PD relationship, phase 1 data
Plasma concentrations of X842´s active metabolite linaprazan determines intragastric acid control (pH >4)
pH level related to plasma
concentration of linaprazan
Efficacy predictable from phase I
Excellent biomarker in phase I to predict clinical outcome in phase II and III (healing of esophagitis).
Mean percentage of time the intragastric pH >4 determines healing rate2)
Note: 1) Kahrilas P, et al (2007). Dent J, et al (2008). 2) Yuan, Thabane & Hunt (2007).
The clinical development program is de-risked by the dose-linear acid control shown in the recently conducted phase I study of X842, as well as by the extensive documentation of X842's active metabolite linaprazan which has been previously studied in some 2,500 individuals.
Cinclus Pharma is working together with regulatory authorities to ensure an optimal regulatory path towards approval of X842. The regulatory guidelines are clear-cut, and an IND process has already been initiated in the US.
Interactions with regulatory authorities
EMA3) or MPA4)
Note: 3) EMA = European Medicines Agency. 4) MPA = Medical Products Agency. 5) IND = Investigational New Drug.
The successful Japanese launch by Takeda of the first P-CAB drug, Takecab, has further substantiated the large unmet medical need and the potential for X842. Compared to Takecab, X842 provides superior acid control.
The planned target segments at launch comprises patients with severe esophagitis (grade C and D), as well as patients with incomplete response to PPIs. The estimated total size of this target population in Europe and the US/Canada, based on epidemiological data, is 18.5 million people, indicating a blockbuster potential for X842.
A first licensing agreement is already in place with Jiangsu Sinorda Biomedicine Ltd, covering China and certain other territories in South East Asia.
There are attractive opportunities to extend the future use of X842 beyond severe esophagitis, particularly into on-demand treatment of GERD, H. pylori eradication, nocturnal GERD symptoms and bleeding ulcers. The X842 prodrug molecule has patent protection until 2029 plus potential extension of approximately five years.