Periodic Reporting for period 1 - Endoprotease 40 (E40) (First ever preventive treatment for celiac disease and gluten sensitivity)
Reporting period: 2023-06-01 to 2024-05-31
Gluten ingestion triggers symptoms in people suffering Celiac Disease and Non-Celiac Gluten Sensitivity (CD & NCGS).
CD affects 1-1.5% of the global population and NCGS 7-10%. Diagnosis rates are increasing, having increased on average 7.5%/year over the past decade and a diagnosed:undiagnosed ratio of 1:7 is estimated.
There is no cure for CD or NCGS, with management of gluten exposure the only option, through a challenging, lifelong and strict adherence to a Gluten Free Diet (GFD).
A GFD is difficult to follow and expensive. Even adhering to a GFD, severe patients can remain symptomatic and all sufferers remain subject to a persistent risk of accidental exposure, e.g. when dining out, due to inaccurately labelled food ingredients and cross-contamination.
Prompt symptoms following gluten exposure include abdominal pain, nausea, vomiting and diarrhoea, etc.
As well as physical symptoms, gluten has a tremendous adverse impact on Quality of Life (QoL), causing social isolation, work/school absenteeism and can trigger / contribute to depression & anxiety for sufferers.
Effective solutions to prevent symptoms related with gluten remain a huge unmet market need.
E40 is a breakthrough 1st-line preventive treatment for CD & NCGS.
E40 has been shown to destroy gluten’s toxic/immunogenic potential in the stomach & intestine, when taken 30 minutes before meals, thus avoiding inflammation and potentially, associated symptoms.
E40 offers significant advantages as it:
1) is fully functional across the stomach & duodenal pH as a stand-alone enzyme, ensuring prolonged & complete gluten digestion;
2) is not systemically absorbed and shows an impeccable safety profile;
3) can be classified as a medical device, shortening time to market and increasing access; and
4) comprises a single enzyme resulting in a clear cost advantage.
E40 will allow CD and NCGS sufferers to enjoy regular everyday activities without the fear of symptomatic accidental gluten exposure as well as reducing the total healthcare cost of these prevalent conditions.
CD affects 1-1.5% of the global population and NCGS 7-10%. Diagnosis rates are increasing, having increased on average 7.5%/year over the past decade and a diagnosed:undiagnosed ratio of 1:7 is estimated.
There is no cure for CD or NCGS, with management of gluten exposure the only option, through a challenging, lifelong and strict adherence to a Gluten Free Diet (GFD).
A GFD is difficult to follow and expensive. Even adhering to a GFD, severe patients can remain symptomatic and all sufferers remain subject to a persistent risk of accidental exposure, e.g. when dining out, due to inaccurately labelled food ingredients and cross-contamination.
Prompt symptoms following gluten exposure include abdominal pain, nausea, vomiting and diarrhoea, etc.
As well as physical symptoms, gluten has a tremendous adverse impact on Quality of Life (QoL), causing social isolation, work/school absenteeism and can trigger / contribute to depression & anxiety for sufferers.
Effective solutions to prevent symptoms related with gluten remain a huge unmet market need.
E40 is a breakthrough 1st-line preventive treatment for CD & NCGS.
E40 has been shown to destroy gluten’s toxic/immunogenic potential in the stomach & intestine, when taken 30 minutes before meals, thus avoiding inflammation and potentially, associated symptoms.
E40 offers significant advantages as it:
1) is fully functional across the stomach & duodenal pH as a stand-alone enzyme, ensuring prolonged & complete gluten digestion;
2) is not systemically absorbed and shows an impeccable safety profile;
3) can be classified as a medical device, shortening time to market and increasing access; and
4) comprises a single enzyme resulting in a clear cost advantage.
E40 will allow CD and NCGS sufferers to enjoy regular everyday activities without the fear of symptomatic accidental gluten exposure as well as reducing the total healthcare cost of these prevalent conditions.
A sensitisation and irritation test was completed, demonstrating E40 to be safe and with no adverse effects.
A Dose Range Finding study ('DRF') has been completed with a dose per body weight equivalent to in excess of 100x the maximum dose planned in the up-coming clinical trials, with no systemic toxicity identified.
Together these results demonstrate a robust safety profile for E40 as we move towards the clinical trial.
In addition, the results of the DRF have informed the planned sub-chronic toxicology studies, commencing imminently, as well as the up coming clinical trials.
From a manufacturing standpoint, significant progress has been made in the manufacturing process of E40 with E40 representative of the commercial form now reliably produced. This is a critical step as it demonstrates the ability to scale-up production to produce effective E40 at commercial scale. Additionally, the E40 produced has demonstrated significantly improved activity levels as well as potential for yet further improvement, with a ratio of E40 to gluten of 1:20 for complete gluten detoxification, i.e. 500 mg E40 are able to degrade 10 g of gluten (note that the gluten content of a regular diet is at least 6-8 g gluten/day).
A Dose Range Finding study ('DRF') has been completed with a dose per body weight equivalent to in excess of 100x the maximum dose planned in the up-coming clinical trials, with no systemic toxicity identified.
Together these results demonstrate a robust safety profile for E40 as we move towards the clinical trial.
In addition, the results of the DRF have informed the planned sub-chronic toxicology studies, commencing imminently, as well as the up coming clinical trials.
From a manufacturing standpoint, significant progress has been made in the manufacturing process of E40 with E40 representative of the commercial form now reliably produced. This is a critical step as it demonstrates the ability to scale-up production to produce effective E40 at commercial scale. Additionally, the E40 produced has demonstrated significantly improved activity levels as well as potential for yet further improvement, with a ratio of E40 to gluten of 1:20 for complete gluten detoxification, i.e. 500 mg E40 are able to degrade 10 g of gluten (note that the gluten content of a regular diet is at least 6-8 g gluten/day).
With the significant advancements in the manufacturing capabilities and activity of the E40 product which can now be produced in its commercial form, and based on the indications of safety and efficacy from the work completed to date, E40 has progressed well on its path to regulatory approval and commercial production.
Focus now shifts to the completion of the toxicological package and clinical trials planned under the grant work programme, using the E40 manufactured to date and further batches planned. In parallel, some of the E40 manufactured to date will be used to demonstrate and understand E40’s precise in vivo safety, efficacy and mode of action, in the HLA-DQ8 mice model of Celiac Disease, generating further valuable experimental evidence and data.
These developments and the progress made reinforce the very tangible reality of E40 and its potential to be the first approved and effective treatment for the prevention of symptomatic gluten exposure in gluten intolerant and gluten sensitive subjects. The submission of the technical file to the Notified Body for risk assessment and approval as a medical device in Europe is on track, i.e. targeting market authorisation and commercialisation in 2026.
Focus now shifts to the completion of the toxicological package and clinical trials planned under the grant work programme, using the E40 manufactured to date and further batches planned. In parallel, some of the E40 manufactured to date will be used to demonstrate and understand E40’s precise in vivo safety, efficacy and mode of action, in the HLA-DQ8 mice model of Celiac Disease, generating further valuable experimental evidence and data.
These developments and the progress made reinforce the very tangible reality of E40 and its potential to be the first approved and effective treatment for the prevention of symptomatic gluten exposure in gluten intolerant and gluten sensitive subjects. The submission of the technical file to the Notified Body for risk assessment and approval as a medical device in Europe is on track, i.e. targeting market authorisation and commercialisation in 2026.