Horizon 2020 – AllergyVAX
Next generation allergen immunotherapy based on specifically modified recombinant hypoallergens
Desentum’s goal is to set a new industry standard on allergy treatment by developing novel immunotherapeutic hypoallergens – so-called allergy vaccines. In the AllergyVAX project, we tested a birch pollen hypoallergen DM-101 (rBet v 1 dm) in a First-in-Human clinical study to evaluate its safety and potential to induce a desired immunological effect, and to obtain a roadmap for further clinical trials. A goal in the project was also to develop a business strategy for partnering and commercialization of DM-101 and the platform technology.
Allergy is a rapidly increasing, global problem that already affects 1 billion people and causes significant social and economic burden. In Europe, allergic rhinitis and asthma cause more than 100 million missed work and school days per year. Allergy is usually managed by avoiding the allergen or by medication that temporarily alleviates the symptoms.
The only disease-modifying treatment available to date is allergen immunotherapy (AIT) where long-term symptom relief is achieved by training the immune system to tolerate allergens. However, typical AIT takes 3-5 years, involves monthly injections or daily drops/tablets and has the risk of serious allergic reactions during treatment. Thus, the popularity of AIT is still relatively low compared to symptomatic drugs.
We have developed a platform technology for creating modified hypoallergens to be used in AIT. It is based on making small, highly targeted modifications to allergen proteins that reduce their ability to trigger allergic reactions during treatment without compromising their efficacy in building tolerance to natural allergens. With these modified hypoallergens, we expect to shorten the injectable AIT treatment from dozens of injections over 3 years to just 3-6 injections over a few months. From the clinically important major birch pollen allergen Bet v 1 we have created DM-101 hypoallergen. In preclinical tests it has shown 100-fold reduction in histamine release compared to natural allergens and induced similar immunological responses in mice that are desired in human AIT.
Project tasks and objectives
In the AllergyVAX project we tested DM-101 for maximum tolerated dose and immunogenicity in allergic patients in a First-in-Human clinical study. The project aimed to facilitate a seamless transition to further clinical development, establishing a basis for product launch with selected partners and advancing other hypoallergens in the pipeline, including product candidates for grass pollen, dog, horse and peanut allergies.
Primary project objectives:
- Demonstrating the safety and immunogenicity of rBet v 1 dm in a clinical setting
- Aligning financial and business development strategies to support market access
- Increase awareness of Desentum’s technology among the allergy community
Primary tasks for achieving the objectives:
Preparation of a regulatory package for clinical trial authorization; discussion with regulatory authorities to ensure compliance
|Phase I/IIa clinical trial||
Testing the safety, tolerability and immunogenicity of Bet v 1 dm in a first-in-human clinical study
Building partnering relationships and market access strategy to ensure seamless late-phase clinical development and commercialisation
|Communication||Communicating the project progress and results to educate the stakeholders and support the business development goals|
AllergyVAX project started in Dec 2018 and ended in Jul 2021. Project duration was 32 months.
The First-in-Human clinical study in birch pollen allergic adults was completed in 2021. The results indicate a positive outcome of the study, although more data will be required for clinical proof-of-concept. It was concluded that the highest of the tested dosing regimens, a biweekly dosing regimen of DM-101 involving 5 ascending doses is safe and well-tolerated by subjects that suffer from seasonal symptoms of birch pollen allergy. Albeit the number of study participants was small, the immunological marker results indicated a favourable change in the markers associated with a protective response.
An unexpected result that derived from the project was new information regarding the impact of formulation on the potency of allergens. In parallel to the AllergyVAX project, formulation development work (not funded by the H2020 grant) has been conducted to exploit this information and produce an improved formulation of DM-101 for the next clinical study. The improved formulation has a potential to bring new properties to the product that can move it further beyond the state-of-the-art. Planning and preparations are ongoing for a next clinical study.
Even though the Covid-19 pandemic and pollen season caused delays, the AllergyVAX project enabled Desentum to successfully complete the First-in-Human clinical study, which is a key to reaching other milestones in the coming months and years. The goal is to set off a change in the way allergies are managed – from treating the symptoms to treating the disease.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 829933.