Development pipeline

Trimodulin (BT-588, IgM Concentrate)

Trimodulin is an innovative polyvalent antibody composition, purified from human plasma. In comparison to standard IgG preparations (IVIG), trimodulin contains relevant amounts of IgM and IgA in addition to IgG.

Trimodulin is in clinical development for the treatment of patients with severe community-acquired pneumonia (sCAP).

Research so far has shown that trimodulin could interfere with a number of mechanisms involved in pathological processes that would otherwise lead to respiratory failure, sepsis, multi-organ failure and finally to death of the patient. Due to the large variety of polyvalent antibodies present in trimodulin, the impaired immune system is supported in various ways. Particularly the IgM component in trimodulin can reduce dysregulated immune responses, preventing the immune system to attack host tissues, in this case the lung. The polyvalent antibodies also bind to various types of pathogens including viruses and bacteria as well as their toxins and support their clearance by the immune system. In this way, trimodulin may prevent progression of disease, including the need for invasive mechanical ventilation and other intensive care procedures.

Publications

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Singer et al. The immunomodulating activity of trimodulin (polyvalent IgM, IgA, IgG solution): a post hoc analysis of the phase II CIGMA trial. Crit Care. 2023 Nov 9; 27(1):436
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Schmidt et al., The Dual Role of a Polyvalent IgM/IgA-Enriched Immunoglobulin Preparation in Activating and Inhibiting the Complement System, Biomedicines (2021) 9, 817.
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Duerr et al.: The novel polyclonal Ab preparation trimodulin attenuates ex vivo endotoxin-induced immune reactions in early hyperinflammation. Innate Immunity 2019, 25(6), 374–388.
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Welte et al., Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study). Intensive Care Med. 2018, 44: 438–448.
[ Link ]

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Shmygalev et al., IgM-enriched solution BT086 improves host defense capacity and energy store preservation in a rabbit model of endotoxemia. Acta Anaesthesiologica Scandinavica 60 (2016) 502–512. doi: 10.1111/aas.12652.
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Welte et al.: Concept for a study design in patients with severe community-acquired pneumonia: A randomised controlled trial with a novel IgM-enriched immunoglobulin preparation – The CIGMA study. Respiratory Medicine 2015, Volume 109, Issue 6, 758 – 767.
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Schmiedl et al.: Evaluation of pharmacokinetics and safety of the IgM enriched immunoglobulin concentrate BT086 in healthy volunteers – results of a dose-escalating single dose phase I study. Br J Clin Pharmacol 2011, 72:1-46, Abstract 40.
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Schmiedl et al.: Evaluation of pharmacokinetics and safety of the IgM enriched immunoglobulin concentrate BT086 in healthy volunteers - results of a multiple dose phase I study. Br J Clin Pharmacol 2011, 72:1-46. Abstract 43
[ Link ]

Clinical trials

Title

Indication

Status

 
Trimodulin (Study 982; CIGMA) Severe community acquired pneumonia Trial completed

A prospective randomized, double-blind, placebo-controlled, multicenter, parallel-group, adaptive group-sequential Phase II Study, to determine the efficacy and safety of BT086 as an adjunctive treatment in severe community acquired pneumonia (sCAP)

Link clinicaltrials.gov
 
Trimodulin (Study 996; ESsCAPE) Severe community acquired pneumonia Trial ongoing

A randomized, placebocontrolled, double-blind, multi-center, phase III trial to assess the efficacy and safety of trimodulin (BT588) in adult hospitalized subjects with severe community-acquired pneumonia (sCAP)