Project overview of the BM4SIT project
BM4SIT stands for “Bet v 1 Mutant for  Specific Immuno Therapy”. The project focuses on birch pollen allergy, the third most common respiratory allergic disease in Europe. Birch pollen allergy is caused by a single major allergen called Bet v 1. Current allergen-specific immunotherapy (AIT) is carried out with birch pollen extracts. It has been demonstrated that AIT can also be effectively performed with just the major allergen Bet v 1 instead of an extract.
The concept of BM4SIT is to administer a mutant of Bet v 1 instead, called BM41 (formerly known as BM4), designed to reduce allergic side-effects but in parallel be more effective in the modulation of the allergic towards an anti-inflammatory immune response.
Current AIT protocols require long-term treatment regimen to be effective. In BM4SIT, the concept of a safe and efficient mutant Bet v 1 will therefore be complemented with an approach to more rapidly cure the allergic immune response. Therefore, vitamin D3, which has pre-clinically been proven to favor anti-inflammatory responses, will be evaluated as novel adjuvant supporting rapid suppression of allergic inflammation.
Safer, better and quicker - therapeutic vaccines will make allergen-specific immunotherapy (AIT) more efficient and more patient-friendly
BM4SIT focuses on birch pollen allergy, the third most common respiratory allergic disease in Europe. In BM4SIT an allergen derivative designed to achieve the overall objective will be tested in AIT, to replace extract-based vaccines. The drug substance that has been developed to this end is BM41 a mutant of the major birch pollen allergen Bet v 1.
The molecule BM41 was designed as a so called "hypo-allergen", meaning that its safety profile is greatly enhanced. On top of that, the BM41 molecule was engineered to be highly efficient for the treatment of birch pollen allergy, as it has increased immunogenicity.
The novel adjuvant vitamin D3 is expected to help to increase treatment efficacy by exploiting its anti-inflammatory properties, allowing earlier onset of treatment effect. BM4SIT will be carried out by a small product-focused multidisciplinary consortium. The nucleus of the consortium is formed by the biotech company Biomay AG, bringing in the relevant background IP on BM41, essential for future protection and exploitation, and the industrial environment and expertise needed to bring academic progress from bench to bedside.
Together with partners from academia, including four expert clinical centers, the consortium is perfectly suited to produce the proposed drug substances and drug products, complying with GMP regulations and to evaluate the new concept in human clinical trials, complying with all GCP requirements.
BM4SIT aims to improve the quality of life of patients with birch-pollen induced respiratory allergy. This shall be accomplished by the decreasing treatment burden (less injection with less side-effects), thus allowing an easier choice away from chronic symptomatic drug use to pharmaco-economically more attractive AIT protocols.
Development of an AIT vaccine for birch pollen allergy
To develop a new AIT vaccine for birch pollen allergy, BM4SIT has been divided into three phases. In phase one, subcutaneously administered vitamin D3 was tested for safety and immune-modulatory characteristics. In phase two, the treatment efficacy of using vitamin D3 as novel adjuvants in combination with an approved birch pollen AIT vaccine (Alutard SQ) successfully used in the clinical daily routine, will be investigated. Following extensive toxicological studies to find a safe dose of the drug product BM41, in phase three, both safety and efficacy will be assessed in a first in man Phase I/IIa DBPC trial with BM41 plus Alutard SQ as an external comparator.
To achieve this, the major tasks are:
Clinical trial with vitamin D3 (primary outcome: safety)
Clinical trial with vitamin D3 combined with birch pollen AIT vaccine (primary outcome: efficacy)
GMP production of the drug substance BM41
Formulation of the drug products BM41
Toxicity studies of the drug product BM41, to establish a no observed adverse effect level (NOAEL) for the drug product BM41
Development of appropriate QC tests for BM41 drug substance and products
F irst in man Phase I/IIa clinical trial with BM41 (primary outcome: safety)