New nonclinical data on BBT-301, a novel small molecular KCa 3.1 inhibitor, and BBT-209, an endogenous GPCR19 agonist, show promise for the treatment of idiopathic pulmonary fibrosis (IPF), according to Bridge Biotherapeutics, which is developing both drugs. The results, announced by news release, were presented at the 6th Annual IPF Summit held recently in Boston, Massachusetts.

BBT-301 fights IPF by controlling ion channels in a selective manner. The results of cell-based biochemistry assays and animal model studies demonstrated a potent antifibrotic effect of BBT-301 as well as its ability to improve pulmonary function and reduce Ashcroft and collagen deposition in a dose-dependent manner.

Lung function recovery in terms of forced vital capacity and pressure-volume curve was also comparable to the current standard of care.

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Prior research has shown that patients with IPF express higher levels of the calcium-activated potassium channel KCa 3.1, and that inhibition of this channel via pharmacological or genetic approaches is able to reduce or even prevent fibrosis.  BBT-301 works by inhibiting the KCa 3.1 channel at an inhibitory concentration of 50% of 6nM, which suggests its inhibitory efficacy is comparable to others in the same class of drug candidates.  

BBT-209 restrains fibrosis by activating GPCR19. Cell-based biochemistry assays and a bleomycin-induced mouse model demonstrated competitive inhibitory effects against IL-1β and TNF-α cytokine expression, as well as a significant anti-inflammatory effect and expression of α-SMA (α-smooth muscle actin).

The study results, along with those of other strong antifibrotic medications such as BBT-887, suggest the potential of therapies combining the standard of care and novel IPF treatments to better address the currently unmet needs of these patients.

Reference

Bridge Biotherapeutics presented non-clinical study results for 2 IPF candidates at the IPF Summit 2022. News release. Bridge Biotherapeutics, Inc; September 1, 2022.

BBT-209 BBT-301 Bridge Biotherapeutics Pulmonologists Researchers