T-Balance® Therapeutics was founded in 2019 under the name OGen GmbH. The biotechnology start-up in Frankfurt/Main and Munich encompasses an international team with a network of renowned partners in the fields of CMC, Regulatory Affairs, preclinical and clinical development. The focus of T-Balance® Therapeutics is apparent from its name – the development of the humanized monoclonal antibody—tregalizumab—which can restore immune system balance to prevent or treat autoimmune disorders and inflammatory conditions.
Tregalizumab selectively activates the immunomodulatory subpopulation of T cells called regulatory T cells or Tregs. Tregs are essential for maintaining peripheral immune tolerance; they suppress autoreactive T cells (i.e. cells targeted against the body’s own structures) and thereby prevent the excessive activation of T lymphocytes seen in autoimmune and inflammatory diseases. Tregalizumab acts early in the inflammatory cascade, providing the opportunity for a novel therapeutic approach aimed at the prevention and treatment of inflammatory conditions.
Tregalizumab binds to its target, CD4, in a unique manner and unlike other molecules in its class specifically activates Tregs. In so doing, tregalizumab does not activate effector T-cells nor does it deplete CD4-positive T-cells, which are crucial for the adaptive immune response.
Therefore, tregalizumab has the potential to help treat a wide variety of autoimmune diseases and conditions associated with the signs and symptoms of inflammation.
Innovative Treatment Approach
Tregalizumab activates regulatory T-cells, which are an attractive target in a variety of T-cell mediated disorders. A better scientific understanding of both the function of Tregs as well as disease pathogenesis fosters an innovative treatment approach for tregalizumab. To unlock tregalizumab´s full potential, the selection of the most appropriate indications and/or disease stages is critical. Furthermore, early intervention may be key to blocking pathological T-cell responses early in the course of disease to potentially prevent the onset or manifestation of a disease.
Unlocking Tregalizumab’s Potential
4 7th International Conference on Infectious Diseases, Bacteriology and Antibiotics. October 12-13, 2020 Prague, Czech Republic. Abstract of Autoimmune Disease Session. URL: https://infectiousdiseases.annualcongress.com/events-list/autoimmune-disease. Cited: 5 June 2020
First milestones passed
Tregalizumab has already undergone intensive scientific and clinical studies in autoimmune diseases and is in Phase 2 clinical development. Historical clinical data from 8 clinical trials are available. In these studies, broad ranges for i.v. and s.c. administration were tested and almost 700 subjects dosed for up to 48 weeks.
Tregalizumab’s mode of action has been tested in preclinical studies using human cellular in vitro models. In vitro testing of tregalizumab on patient cells with allergic asthma has revealed a very promising immunomodulatory potential for this therapeutic indication.
Altogether, the preclinical evidence and a favorable safety and tolerability profile of tregalizumab justified proceeding to a Phase 2 clinical study in a new indication (asthma) without the need for a Phase 1 study.
The next milestone
A Phase 2a study in allergic asthma has recently been completed. The design of this PoC study is well-established and standardized. It utilizes an allergen challenge approach to measure bronchoconstriction. This concept has been used in other successful clinical development programs. Clinical efficacy measured during allergen challenge studies can be considered predictive for endpoints in pivotal studies.
As of January 2022, the last patient visit was conducted. The results of the proof-of-concept study in asthma are expected later this year.
1 Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204-22
2 Nunes et al. Asthma Research and Practice (2017) 3:1
3 Global, regional and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392:1736-88.