Our lead asset

Linaprazan glurate

Our drug candidate represents a new and novel mode of action with superior efficacy potential and pharmacokinetic profile. Linaprazan glurate is a Potassium-Competitive Acid Blocker (P-CAB) and a prodrug of linaprazan, a substance initially developed and tested by AstraZeneca. The gastric acid control ability of linaprazan glurate has in studies shown to be superior to current medication.

Linaprazan glurate is a P-CAB and a prodrug of linaprazan, a substance initially developed and tested by AstraZeneca. Linaprazan glurate represents a game changing generation of Gastric Acid Blockers and therapy, building on world leading industrial tradition.

Linaprazan glurate is addressing a large unmet medical need, estimated to over 18 million patients in Europe and North America. The main target groups are patients with severe eGERD not adequately treated with available therapy. Linaprazan is the active metabolite in linaprazan glurate.

History and expected milestones

During 2001-2005 AstraZeneca performed phase I and phase II clinical studies on product candidate linaprazan with the intention to develop the successor to Losec and Nexium. As not all patients are properly healed by existing medication, AstraZeneca identified an unmet medical need which led to the launch of a P-CAB development project.
Comprehensive data from 23 phase I studies including more than 600 subjects and two phase II studies including approximately 2000 patients shows that linaprazan was well tolerated, with a fast onset of action and full effect at first dose.
In 2005 AstraZeneca decided to close the linaprazan project. The rights of the prodrugs of linaprazan were later acquired by two of the founders of Cinclus Pharma.

Linaprazan glurate shows promising results

The prodrug of linaprazan, linaprazan glurate has a longer half-life in the body compared to linaprazan. It shows total control of the gastric acid production and is tailored for patients with severe eGERD.

Clinical development in brief

Phase I clinical trials are completed. Phase II are ongoing within a de-risked clinical development program based on:

Precedent trials with >~2,500 subjects
Excellent Biomarker
Linear correlation between plasma concentration and acid control

Indication aspiration

The indication aspiration for linaprazan glurate is the treatment of erosive Gastroesophageal reflux disease (eGERD) all grades A-D including healing, maintenance of healing to prevent relapse, and relief of symptoms. The main target groups of linaprazan glurate are patients with severe eGERD (esophagitis or erosive GERD) and patients who are not adequately treated with available therapy.

Patients:

with severe eGERD
with eGERD where PPIs are not sufficient in need of improved symptom relief and quality of life

Linaprazan glurate is outperforming linaprazan

Issues highlighted during the linaprazan project are now solved with the prodrug linaprazan glurate.

Issue 1 with linaprazan: Too short acid control

Linaprazan was quickly eliminated from the body and had too short duration of acid inhibition. To achieve long acid control linaprazan had to be overdosed. As a result, it was not possible to show superiority.

Solution:
This was accomplished with linaprazan glurate and shown in animal studies and in two phase I studies

Issue 2 with linaprazan: Cmax levels too high

The resulting Cmax levels were on average 20 times higher than the level required for full inhibition of acid secretion, resulting in increases in liver transaminases in a few patients.

Solution: Administration of linaprazan glurate results in substantially lower Cmax values compared to linaprazan, which minimize the load to the liver.

A long duration effect is already accomplished with linaprazan glurate in toxicological studies and in two phase I studies. A solid oral formulation is in place and the next generation oral formulation is in development, expected to be finished by phase III.

Mode of action P-CABs

Potassium-Competitive Acid Blocker (P-CAB)

P-CABs inhibit the proton pump but at a different site and through a different mechanism of action than proton pump inhibitors (PPIs). P-CABs interact with the potassium channel adjacent to the proton pump. They bind ionically, unlike PPIs, which bind covalently. This means that the binding action of P-CABs is potentially reversible. These agents have a faster onset of action than PPIs, and they have a more flexible action in inhibiting acid secretion.

Source: https://www.gastroenterologyandhepatology.net

P-CABs like linaprazan glurate works differently from the traditional PPI-based drugs like Losec and Nexium. Learn more on how they manage to block the acid to maintain a normal pH here.