Proteostasis Therapeutics, Inc., recently presented new and promising early data on its genotype-agnostic amplifier and novel corrector of the cystic fibrosis transmembrane conductance regulator (CFTR), the protein defective in cystic fibrosis (CF).
The data, from preclinical studies, were presented in two posters at the 13th Annual European Cystic Fibrosis Society (ECFS) Basic Science Conference, held March 30–April 2, 2016, in Italy. The first was titled “Characterization of CFTR amplifiers, mutation-agnostic modulators that increase protein levels and complement other CF therapeutic modalities” and addressed the amplifier; a second poster, “A novel corrector for F508del-CFTR that complements existing CFTR modulators in vitro,” described a corrector for a specific CFTR mutation.
Data in the first presentation suggested that the CFTR protein amplifier has the potential to restore lung function to near-normal levels in patients with varied gene mutations. The new class of modulator proposed by the company, an amplifier, increases the levels of immature CFTR protein available for other modulators, like potentiators and correctors, to act upon.
Specifically, researchers found that amplifiers stabilize the CFTR mRNA, and increase the levels of immature CFTR, the substrate for additional modulators. Moreover, the amplifiers seem to work across CFTR genotypes, and demonstrate activity in non-lung tissues and in vivo. They think this new class of drugs can help patients who fail to improve using current drug therapies, or who have rare mutations with no targeted therapies.
The second presentation focused on the company’s corrector, which has shown properties that differentiate it from other correctors, such as VX-661 or lumacaftor. The drug was shown to increase levels of mature CFTR protein, and to improve in vitro CFTR function when it is dosed along with other modulators, potentiatorsm and the company’s amplifier.
“We believe we have the potential to dramatically improve therapeutic outcomes for patients with cystic fibrosis,” Po-Shun Lee, MD, executive vice president and chief medical officer of Proteostasis Therapeutics, said in a press release. “The data not only validate the use of our novel CFTR amplifiers in combination with existing therapies such as Orkambi and Kalydeco, but they also represent an important early milestone in developing a new and possibly game-changing triple combination therapy for those living with the disease.”