Experimental Peptide Combined With Ofev Reduced IPF Symptoms in Mice

Experimental Peptide Combined With Ofev Reduced IPF Symptoms in Mice
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The combination of CB5138-2 — an experimental peptide, or small protein —  and Ofev (nintedanib) reduced symptoms of idiopathic pulmonary fibrosis (IPF) better than Ofev alone in a preclinical study.

Together, CB5138-2 (developed by CohBar) and Ofev (an approved IPF therapy marketed by Boehringer Ingelheim) reduced fibrosis, inflammation, collagen accumulation, and the presence of pro-inflammatory molecules in the lungs of an IPF mouse model after 14 days of treatment.

“The new data provide clear evidence that the unique mechanism of action of CohBar’s antifibrotic peptides has the potential to be combined effectively with an existing treatment to achieve even greater effects,” Kenneth C. Cundy, PhD, CohBar’s chief scientific officer, said in a press release.

CB5138-2, along with CohBar’s other candidate compounds, are therapeutic peptides derived from mitochondrial DNA.

Best known as the powerhouses of the cell, mitochondria are small organelles found inside cells that play key roles in numerous cellular processes. Mitochondrial dysfunction occurs in several diseases, including IPF.

Mice models of IPF were treated with either placebo, CB5138-2, Ofev, or an Ofev-plus-CB5138-2 combination.

CohBar’s technology platform is based on the screening of mitochondrial peptides for those with therapeutic potential. The company engineers these naturally-occurring peptides to optimize their drug-like properties. The engineered peptides are referred to as “analogs.” Using this strategy, the company has identified a family of peptides with anti-fibrotic potential.

“We previously demonstrated the efficacy of CB5138 Analog peptides administered alone in both the prevention and treatment of fibrosis in preclinical models of IPF, and we now have compelling data further supporting their clinical potential,” Cundy said.

The new data shows that, compared to IPF mouse models treated with placebo or Ofev alone, a 14-day treatment with CB5138-2 plus Ofev combo resulted in a greater reduction in lung fibrosis — as assessed through the Ashcroft lung fibrosis score — as well as in inflammation, secretion of key pro-inflammatory molecules, and collagen production and accumulation in the lungs.

“We plan to present [these] data in an upcoming [key opinion leader] meeting as we continue to move the program towards final selection of a clinical candidate,” Cundy said.

The online meeting will take place at 2 p.m. ET, Nov. 6. Those interested can register for the event here.

“Despite the current availability of two approved drugs, nintedanib and pirfenidone (Esbriet), IPF patients are still dying of respiratory failure and there is a major unmet medical need for better treatments,” said Toby Maher, PhD, professor of medicine at the Keck School of Medicine.

“It is anticipated that any new drug for IPF will be used in conjunction with the current standard of care,” Maher added. “These exciting new preclinical results suggest that combination of CohBar’s peptides with nintedanib has the potential to achieve enhanced effects in IPF patients.”

Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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