Allergens or irritants?

LUND, Sweden—SenzaGen, which focuses on replacing animal experiments with in-vitro genetic testing to determine the allergenicity of chemicals, has signed a collaboration agreement with global biopharmaceutical company AstraZeneca. The research project will run for 12 to 18 months and is in collaboration with AstraZeneca Gothenburg, contributing to the EU Horizon 2020 project granted to SenzaGen for the development of an in-vitro respiratory sensitization test.

The collaboration will test and develop SenzaGen’s sensitization test, GARDair, in order to distinguish between allergens and irritants in the respiratory tract. The objective is the validation of in-vitro toxicological tests that could be applied to the discovery of new treatments for respiratory diseases without respiratory tract irritation as a side effect.

In the collaboration, SenzaGen will build on its technology platform GARD, with the help of AstraZeneca’s well-documented substance libraries, to develop a new genomic signature to distinguish allergens from irritants in the respiratory tract, something that is not possible today with in-vitro methods. GARD examines and finds allergens in chemicals and medicines through a special technology in accordance with the international 3Rs principle—reduce, replace and refine—as an alternative to animal testing. AstraZeneca will provide the substances and correlating in-vivo data, and SenzaGen will perform the cellular and bioinformatics work.

GARD is a group of tests for assessing chemical skin sensitizers. The tests, which reportedly have 90-percent reliability, make use of genetic biomarkers for more than 200 genes that cover the entire immune reaction and are relevant to predicting the risk of hypersensitivity. This compares with the current predominant test method, experiments on mice, which has a reliability rating of 72 percent.

SenzaGen’s tests are also capable of measuring the potency of a substance’s allergenic properties. Consequently, GARD tests provide a much more comprehensive basis for determining whether a substance should be classified as an allergen than current testing methods.

“The industry in general is moving away from animal testing,” explained Anki Malmborg Hager, CEO of SenzaGen. “The 3R initiative is playing a significant role in all companies using animal testing, and the regulatory organizations are working to update regulatory requirements.”

She added, “The challenge with in-vitro methods is that they often simplify the complex reality due to the necessity of using a limited number of read-out parameters. By using genomics technology, which GARD is based on, we get a simple model reflecting a complex reality. Also, since GARD is based on human cells, it is highly relevant, as compared to animal models. In the case of respiratory testing, this is especially interesting, since no in-vitro tests are available.”

“During our research and drug discovery activities, it is important to be able to identify and mitigate potential toxicological issues as early as possible, to ensure our novel candidate drugs have the right safety profile for patients,” said Jorrit Hornberg, director of discovery safety at AstraZeneca Gothenburg. “This requires in-vitro toxicological methods that are properly validated for their predictivity of clinical toxicity and that are compatible with integration into the drug discovery process.”

According to Hornberg, “By combining SenzaGen’s technological expertise and our experience with inhaled compounds, we aim to develop a novel method to investigate whether novel drug-like molecules induce similar genomic signatures as known respiratory irritants. That could ultimately be applied to steer away from a potential irritancy hazard and enable the discovery of safer drugs for patients.”

“This collaboration with AstraZeneca is a milestone for SenzaGen. It shows that leading pharmaceutical companies see the potential of next-generation testing and that this testing has considerable industrial value. Furthermore, the collaboration will provide SenzaGen with valuable knowledge and will help to refine and develop our GARD test for further commercial opportunities,” Malmborg Hager concluded.

SenzaGen makes it possible to replace animal experiments with in-vitro genetic testing to determine the allergenicity of the chemicals people come into contact with in their daily lives, in cosmetics, pharmaceuticals, food products and dyes.

SenzaGen sells its tests in Sweden and the United States, and the company sells through partners in several other countries. Over the next few years SenzaGen will expand geographically, make alliances with more distribution partners and launch further unique tests.

AstraZeneca focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas: oncology, cardiovascular and metabolic diseases and respiratory. The company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.