Clinical development

Clinical development

The Phase II study was initiated in Q3 2021 within a de-risked clinical development program based on results from Phase I studies and precedent trials on its active metabolite, linaprazan. Based on literature data and the results from the completed Phase I studies, excellent biomarkers lower the development risk moving forward. These biomarkers were applied in the design of the Phase II study, with the primary endpoint to optimize the precision of the dose selection for the upcoming Phase III studies. The LEED Phase II study was completed in Q4 2022, and "for patients with moderate to severe eGERD, LA grade C/D, the highest four-week healing rate in a linaprazan glurate dosing group was 89%, compared to 38% in the lansoprazole group." Phase III studies are planned for H2 2023.

Clinical trials on linaprazan glurate – Phase I to Phase III

Phase I

Phase I was initiated in February 2017 and recruitment in the "first-in-human study" was finalized in Q4 2017. Three Phase I clinical trials are completed. Additional Phase I studies are ongoing and planned. All studies so far showed that linaprazan glurate is safe and well tolerated.

Phase II

Phase II was initiated in H2 2021 within a de-risked clinical development program based on preceding trials with the active metabolite linaprazan and completed in Q4 2022 with successful results. The primary objective was to support the selection of the optimal dose for the Phase III studies based on dose-dependent healing rates of erosive esophagitis.

The program is based on:

• Precedent trials that exposed ~2,600 subjects, to the active metabolite of linaprazan glurate

• Excellent biomarker available

• Strong correlation between plasma concentration and pH-control

Phase III

Phase III is to be initiated in H2 2023.

Studies performed on linaprazan (the main metabolite)

Comprehensive data from 23 Phase I studies that exposed more than 600 subjects and two Phase II studies that exposed approximately 2000 patients to the active metabolite show that linaprazan was well tolerated, with a fast onset of action and full effect at the first dose. Linaprazan is the active metabolite of linaprazan glurate.

Phase I – Three studies completed

Dose-related pH control and an excellent biomarker are significant results from the completed Phase I studies.

Overview of SAD/MAD study

Study of single ascending dose (SAD) and Multiple ascending dose (MAD) performed in Sweden.

Primary objective and results

Linaprazan glurate was safe and well tolerated. No serious adverse event (SAE) occurred after dosing.

• Dose related pharmacokinetics

• Dose related acid inhibition and clear PK/PD relationship

• No effect of food was detected

• Study defined maximum dose was reached

• Gastric acid inhibition was maintained over 24 hours at certain dose levels

Description

• Single and multiple ascending dose

• Liquid formulation

• First-in-human design

• Gov. identifier: NCT03105375

Endpoints

• Frequency of adverse events, lab results and vital signs

• Standard PK parameters

• Dose limiting toxicity

• PK/PD where PD is intragastric pH over 24h

Number of patients

• In total, 28 subjects were dosed of which 9 subjects were dosed more than once

• Performed by CTC Clinical Trial Consultants, Uppsala Sweden

Timetable

Initiated in February 2017. Final study report in February 2018.

Phase II design

Primary objective

The primary objective of the study was to support the dose selection of linaprazan glurate for Phase III studies based on four weeks of healing of esophagitis.

Secondary objectives

• Evaluate the safety and tolerability of linaprazan glurate compared to PPI

• Compare the symptom response after four weeks with four dose levels of linaprazan glurate compared to PPI

• Model the optimal dose of linaprazan glurate using healing rates and PK data in patients dosed with linaprazan glurate

Description

A multicenter, randomized, double-blind, active comparator-controlled, parallel-group design five-arm study on patients with reflux esophagitis grade C or D and patients still unhealed after eight weeks of standard treatment healing course with PPI.

The double-blind part is four weeks followed by another four weeks of open-label PPI.

Endpoints

• The primary endpoint is the healing rates of eGERD after four weeks treatment

• Evaluate the safety and tolerability of linaprazan glurate

• Symptom response during and after eight weeks treatment

• Model the optimal dose of linaprazan glurate for Phase III programme

Number of patients

• At least 200 evaluable patients

• Approximately 60 sites

• 7-8 countries in Europe and the US

Timetable

First Patient First Visit (FPFV) in H2 2021 and Last Patient Last Visit (LPLV) in H1 2022.

*C-max is a numerical value that describes the maximum concentration of the drug in the blood.