|Landos Biopharma, Inc., an emerging biopharmaceutical company focused on developing improved treatments for autoimmune diseases, announced the publication of findings on the mechanisms of action for its top lead candidate, BT-11, in Inflammatory Bowel Diseases, the Official Journal of the Crohn's & Colitis Foundation. The study concludes that through the activation of the Lanthionine Synthetase C-Like 2 (LANCL2) pathway, BT-11 induces changes in the interface of inflammation and metabolism within immune cells in the gut that are critical to provide lasting therapeutic efficacy against inflammatory bowel disease (IBD). These changes in metabolism enhance regulatory CD4+ T helper cell responses and promote lasting therapeutic actions locally within the gut. The mechanistic findings demonstrate the translatability of the therapeutic efficacy of BT-11 to the clinic. |
The two primary clinical manifestations of IBD - Crohn’s disease and ulcerative colitis (UC) - afflict 2 million North Americans and 5 million people worldwide, with nearly 15% growth over the last five years. There is an unmet clinical need for safer, more effective medications for these diseases as currently marketed therapeutics have a number of drawbacks: they only benefit a small number of the overall population, lose response effectiveness, or cause high rates of side effects, including cancer, infection and death.
“Oral activity, local action in the gut, and novel mechanism of action are the holy grail of IBD therapeutics. BT-11 and the LANCL2 pathway offer a unique opportunity to completely disrupt the IBD therapeutics market,” said Dr. Josep Bassaganya-Riera, Chairman and CEO of Landos. “This publication illustrates that BT-11 shows potential to be a powerful oral IBD therapeutic that targets LANCL2 and modulates the interactions between immunological and metabolic signals in immune cells creating a favorable regulatory microenvironment in the gut. As these data demonstrate that BT-11 targets only the gut and show a benign safety profile without the concerns of systemic exposure, we will be able to safely escalate dosing in our planned clinical trials and meet planned endpoints for efficacy and safety. We are about to enter the clinic with Phase 1 trials by mid- 2018 and address the significant unmet clinical need of 5 million people afflicted by Crohn’s disease and UC around the world. We are confident that BT-11 has an enormous potential to transform patient outcomes.”
The study, Activation of LANCL2 by BT-11 Ameliorates IBD by Supporting Regulatory T Cell Stability through Immunometabolic Mechanisms, was authored by researchers at Landos. The study found evidence that in mouse models of IBD, BT-11 demonstrated therapeutic activity across multiple levels of disease severity. Importantly, this study demonstrates that the mechanisms of action identified in mouse models translate to human cells obtained from Crohn’s and UC patients in terms of LANCL2 specificity, regulation of critical cytokines involved in IBD, modulation of effector CD4+ T helper cell responses and enhancement of regulatory T cells (Tregs), and activation of immunometabolic pathways. Finally, with a benign safety and toxicology profile at doses up to 1,000 mg/kg, BT-11 may provide a novel approach without dose-limiting safety issues of current or investigational drugs.
Details from the study:
• Findings define a novel immunometabolic mechanism of therapeutic action of BT-11 in IBD through LANCL2.
• Therapeutic efficacy of BT-11 validated using three well-established models encompassing chemical, cellular and genetic methods of IBD induction in this study. Landos has data on therapeutic efficacy in 5 mouse models of IBD.
• BT-11 consistently alters the profile of CD4+ T cells away from inflammatory subtypes that function as the drivers of Crohn’s and UC, and toward regulatory subtypes (Tregs) that promote homeostasis and mucosal healing. Importantly, oral dosing with BT-11 provides greater responses in these models than TNF-a blockers, 5-ASA and GED0301.
• Data show that BT-11 upregulates and rescues low-level expression of LANCL2 in the GI tract, restoring any functional abnormalities induced by inflammation in IBD.
• Results support evidence that BT-11 is capable of suppressing inflammation across multiple levels of disease severity
oBT-11 reduces production of two prominent inflammatory cytokines, TNFα and IFNγ, in cells obtained from Crohn’s disease patients with moderate to severe disease.
Landos Biopharma, Inc., an emerging biopharmaceutical company focused on developing improved treatments for autoimmune diseases, announced the publication of findings on the mechanisms of action for its top lead candidate, BT-11, in Inflammatory Bowel Diseases, the Official Journal of the Crohn's & Colitis Foundation. The study concludes that...