CohBar’s New Mitochondrial Peptide Prevents, Slows Disease Progression in IPF Mouse Model

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Cohbar’s new investigational mitochondrial peptide (a small protein) called MBT#2, not only prevented scarring (fibrosis), but also slowed disease progression when fibrosis was already established in a mouse model of idiopathic pulmonary fibrosis (IPF), according to preclinical data.

The new data was shared on the company’s website as an update on its anti-fibrotic program, and will be presented at an upcoming scientific meeting in 2020.

Mitochondria are small organelles inside cells that are involved in key cellular processes, such as the production of vital energy; mitochondrial  dysfunction is associated with several diseases, including IPF.

Cohbar’s technology platform was designed to identify therapeutically-relevant peptides produced from mitochondrial DNA, and develop them into mitochondria-based therapeutics (MBT). This platform has led to the identification of a family of peptides with anti-fibrotic potential.

These molecules are being evaluated in mouse and cellular models of IPF. In the fibrosis-induced mouse model of IPF, mice are given bleomycin, an anti-cancer drug used to trigger pulmonary fibrosis in rodents. IPF’s cellular model consists of human lung cells grown in the lab and exposed to TGF-β1, a pro-fibrotic molecule that also plays a central role in IPF progression.

Previous preclinical data showed that one of these peptides, MBT#2, significantly prevented the development of lung fibrosis in the fibrosis-induced mouse model when treatment was administered immediately after fibrosis induction and for 21 days. This protective effect against fibrosis was accompanied by an almost normalization of lung inflammation.

Also, MBT#2 significantly lowered the levels of fibrosis biomarkers — including alpha-smooth muscle actin (ɑ-SMA) and collagen type I and III — in the cellular model of IPF.

Now, new preclinical data has shown that MBT#2 induced promising therapeutic effects in the same IPF mouse model when treatment was given and fibrosis was already established in these mice (seven days after fibrosis-induction).

Results showed that 14 days of MBT#2 treatment led to the stabilization of body weight loss in these mice, and a significant reduction in lung fibrosis, inflammation, and collagen levels, compared to untreated mice. Importantly, these effects were similar to those reported with Ofev (nintedanib), an approved anti-fibrotic therapy for treating IPF.

MBT#2 also was found to suppress the transformation of healthy human lung fibroblasts into pro-fibrotic myofibroblasts — a hallmark of IPF.

“With these new data, CohBar’s novel peptide has now demonstrated both prophylactic [preventive] effects on fibrosis prevention, and therapeutic effects on slowing progression of established fibrosis in widely-used preclinical models,” Ken Cundy, PhD, CohBar’s chief scientific officer, said in a press release.

Steven Engle, CohBar’s CEO, said they are “encouraged by the confirmatory results for this novel peptide [MBT#2] in the setting of established lung fibrosis.”

“These new results also suggest potential for efficacy in other fibrotic and inflammatory diseases, and further illustrate the potential of the mitochondrial [DNA] as a source of novel therapeutics for a broad range of diseases,” Engle said.

The company is continuing to evaluate the therapeutic potential of this new family of molecules in IPF and other fibrotic diseases to identify an optimized therapeutic candidate.

CohBar’s lead investigational molecule, CB4211, has entered a Phase 1b clinical study for the treatment of nonalcoholic steatohepatitis (NASH) — a type of liver disease associated with liver fat accumulation — and obesity, after showing promising preclinical data. CB4211 is the first therapeutic candidate based on a mitochondrial-derived peptide to be evaluated in a clinical trial.