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Abstract Number: 0471

Therapeutic Efficacy of BT-104, an Oral LANCL2 Agonist, for the Treatment of Systemic Lupus Erythematosus

Andrew Leber, Raquel Hontecillas, Nuria Tubau-Juni, Sarah Fitch, Jyoti Chauhan and Josep Bassaganya-Riera, Landos Biopharma, Blacksburg, VA

Meeting: ACR Convergence 2021

Keywords: immunology, Mouse Models, Lupus, Systemic lupus erythematosus (SLE), Treg cells

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Session Information

Date: Saturday, November 6, 2021

Session Title: Abstracts: SLE – Animal Models (0470–0473)

Session Type: Abstract Session

Session Time: 11:15AM-11:30AM

Background/Purpose: Systemic lupus erythematosus is a complex disease in which the immune system is dysfunctional at multiple levels including impaired regulatory responses, altered self-antigen processing and increased autoantibody production. LANCL2 is a novel anti-inflammatory target that has been first targeted by a gut-restricted compound, omilancor (BT-11), currently in Phase II/III clinical development for inflammatory bowel diseases. BT-104 functions through similar immunometabolic mechanisms, increasing the suppressive capacity and stability of regulatory CD4+ T cells while also supporting the metabolic demands of autophagy in phagocytes.

Methods: Based on these immunological effects, we evaluated oral BT-104 in three mouse models of lupus: the NZB/W F1 model, the MRL/lpr model and the bm12 adoptive transfer model. Mice were treated daily with oral BT-104 from ages 24 to 36 wk in the NZB/W F1 model, from ages 12 to 18 wk in the MRL/lpr model and from 1 to 2 wk post-transfer in the bm12 model. Therapeutic efficacy was evaluated by proteinuria, anti-nuclear antibody titers, immune cell changes in the blood and spleen, and histological inflammatory changes in the kidney. Further, the MRL/lpr model was used to identify global transcriptional signatures of BT-104 in blood and spleen after oral treatment. The translational efficacy of BT-104 was evaluated in PBMCs from SLE patients in vitro.

Results: In the NZB/W F1 and MRL/lpr models, BT-104 protected against worsening from baseline in proteinuria grade in greater than 90% of mice, improved proteinuria grade in roughly half of mice, and reduced anti-nuclear antibody levels by three-fold. BT-104 reduced overall histological score in the kidneys, including improvement in interstitial inflammation, glomerular proliferation, and cellular crescents. Immunologically, across all three models, BT-104 significantly reduced IL17+ and IL21+ CD4+ T cells in the spleen while significantly increasing CD25+ FOXP3+ regulatory CD4+ T cells (Treg). BT-104 significantly reduces the production of interferon alpha in human PBMCs from SLE patients in response to general (PMA and ionomycin), TLR7 (gardiquimod) and CpG oligonucleotide (ODN2395) stimuli.

Conclusion: Based on the preclinical data generated, BT-104 is a promising therapeutic for systemic lupus erythematosus and other rheumatic conditions. BT-104 is expected to enter Phase I clinical testing in normal healthy volunteers in Q4 2021.


Disclosures: A. Leber, Landos Biopharma, 3; R. Hontecillas, Landos Biopharma, 3, 4, 11; N. Tubau-Juni, Landos Biopharma, Inc., 3, 11; S. Fitch, Landos Biopharma, 3; J. Chauhan, None; J. Bassaganya-Riera, Landos Biopharma, 3, 4, 8, 11.

To cite this abstract in AMA style:

Leber A, Hontecillas R, Tubau-Juni N, Fitch S, Chauhan J, Bassaganya-Riera J. Therapeutic Efficacy of BT-104, an Oral LANCL2 Agonist, for the Treatment of Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/therapeutic-efficacy-of-bt-104-an-oral-lancl2-agonist-for-the-treatment-of-systemic-lupus-erythematosus/. Accessed January 31, 2023.
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