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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - SOMIT (Leveraging a novel platform technology to develop a first-in-class immunotherapy for Celiac Disease)

Teaser

Summary

Celiac Disease is a debilitating autoimmune disorder that is caused by intolerance to gluten. Although it is the most common genetically-based food intolerance in the world, there are currently no therapeutics available to treat patients, which leaves them at the only \'treatment\' option: a gluten-free diet. Over the past decade, persistent efforts from patients, family members, advocacy groups, physicians, and researchers have helped increase awareness for Celiac Disease (CD) and improved the availability of gluten-free foods. Although this has had a tremendous social impact on the lives of CD patients, not a single therapeutic has been approved so far. Around 1% of the global population is affected by CD and with over 8 million patients in the US and EU alone it represents a high volume market. Epidemiological studies have revealed that the incidence of CD is steadily increasing by around 3% per year.

WIth the development of a first-in-class antigen-specific immunotherapy against Celiac Disease, Allero would like to offer the CD patients a disease modifying treatment option. This would would have an important social impact for these patients, as they will become (again) tolerant to gluten and do not have to fear any incidental uptake of gluten any more.

The solution that the Allero therapeutic approach will offer, includes:
- Non-invasive and patient-friendly treatment including infants below 5 years of age;
- Short-course treatment that reinstates tolerance (long-lasting effect);
- It enhances tolerance induction by targeted stimulation of proper immune cells;
- Optimal retention of therapeutic agent at common tolerance induction site: the oromucosa;

In this feasibility study under the SMEi H2020 program, the most important objective of Allero is to obtain a pre-clinical Proof of Concept that allows the company to start developing a first-in-class antigen-specific immunotherapy against Celiac Disease. The project consists of a 6-month multi-disciplinary feasibility study with the following objectives: (1) experimentally demonstrate Proof of Concept for the novel therapeutic; (2) produce a detailed (pre)clinical development plan that considers all safety, efficacy, manufacturing, and regulatory requirements; (3) strengthen and expand the current IP position; and (4) consolidate all current and future findings into an investor-ready Business Plan.

Work performed

The feasibility study conducted by Allero Therapeutics, as funded under the SMEi H2020 program, was considered a great success for the company. Allero was able to show that the concept of oromucosal antigen-specific immunotherapy (SOMIT) works in an experimental setting, resulting in an early indication that short-course immunotherapies may work in patients, in particular in Celiac Disease.

The experimental work under the project was executed by two leading research institutes, VRI (CZ) and LUMC (NL). In Celiac Disease patient material we were able to show that there is no stimulatory effect on pro-inflammatory T-effector cells of these patients but rather an inhibitory effect on these effector cells. In a relevant pre-clinical model, we further demonstrated that the SOMIT components are released at the mucosal surface, are actively taken up by cells of and/or penetrate by diffusion into the mucosal tissue and most likely migrate to the draining lymph nodes, which are the T- and B-cell active centres that determine the outcome of the immune responses. In addition to obtaining this proof of concept, the IP position was strengthened, a preclinical and clinical development roadmap was constructed, and thorough market studies were conducted for Celiac Disease, other autoimmune diseases, and allergies, confirming the huge medical need and market for such a disease modifying approach in these indications.

The success of this funded program was consolidated in a comprehensive investor-ready business plan. Based on this plan a significant seed investment from a specialized institutional investor (Swanbridge Capital) was secured in April 2019, attracted by the huge potential of the SOMIT approach. This capital injection will help Allero to further develop its promising SOMIT therapeutic approach for Celiac Disease patients and other autoimmune disease and/or allergy indications for which no (effective) treatments exist.

Final results

Treatment of allergy and auto-immune diseases is currently only symptomatic by treating the direct effects of the disease. Currently, there are no treatments available that result in a diseases modifying effect, making the patient tolerant to the allergen(s) and auto-antigen(s) that cause the disease. With this feasibility project, Allero will show in a pre-clinical setting that obtaining such disease modifying effect will be possible with its proprietary SOMIT treatment approach. We expect to show a pre-clinical Proof of Concept in patient material and other experimental models. With obtaining such Proof of Concept, Allero will also have created the opportunity for the SOMIT treatment approach to be used for multiple Allergy and AutoImmune Disorder (AID) indications.

The impact for the patients will be tremendous, as they do not need to be on gluten-free diets any more and/or take medications that only treat the direct effects of the disease. The CD therapeutics market currently consists of (generic) drugs (e.g. corticosteroids) that merely offer symptomatic treatments. In the long-term, with the approval of safe and effective therapeutics such as SOMIT, the potential market for CD therapeutics is estimated in the billions. Willingness to pay from healthcare payers is already demonstrated by the (partial) coverage of gluten free foods in several European countries.