Proteostasis Therapeutics — a pharmaceutical company that develops small molecule drugs for cystic fibrosis (CF) — recently announced the latest pre-clinical results from its first-in-class genotype-agnostic amplifier and a novel corrector of CFTR (the defective gene in CF) at the 13th Annual European Cystic Fibrosis Society (ECFS) Basic Science Conference in Italy.

“We are strongly encouraged by our early findings and the potential implications for improving the lives of people with cystic fibrosis,” Meenu Chhabra, president and CEO of Proteostasis Therapeutics, said in a press release.

“Patients treated with currently available therapies still struggle to achieve full lung function, while many are not receiving treatment at all due to rare mutations of the disease. The results from our preclinical studies show the potential of our CFTR amplifier to restore lung function to near-normal levels not only in patients with the most common gene mutation found in cystic fibrosis, but across multiple gene mutations,” Chhabra said.

Proteostasis Therapeutics revealed its results in a poster presentation at the conference titled “Characterization of CFTR amplifiers, mutation-agnostic modulators that increase protein levels and complement other CF therapeutic modalities.”

The scientists demonstrated a new type of modulator — an amplifier — which can increase immature CFTR protein levels so that correctors and potentiators can act upon them.

Here is a summary of the researchers’ key findings:

• The amplifiers increase immature CFTR protein levels and can stabilize CFTR mRNA;
• The amplifiers increase substrate levels for more modulators;
• The amplifiers function across various CFTR genotypes;
• The amplifiers show activity in-vivo and in non-lung tissues.

Their first studies could demonstrate the ability of the novel amplifiers to enhance the CFTR translation across various CFTR mutations. Amplifiers were also used to activate other modulators in the treatment of cystic fibrosis.

The company’s second poster detailed a new corrector, which is different from other clinical-phase correctors like lumacaftor or VX-661. Titled “A novel corrector for F508del-CFTR that complements existing CFTR modulators in vitro,” the poster showed that the corrector could significantly increase the levels of mature CFTR protein. In addition, in vitro CFTR activity was increased after the corrector was added with other modulators, like lumacaftor, potentiators, and its amplifier.

“We believe we have the potential to dramatically improve therapeutic outcomes for patients with cystic fibrosis,” said Po-Shun Lee, M.D., executive vice president and CMO of Proteostasis Therapeutics. “The data not only validates 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.”