QR-010 is an experimental molecule developed by ProQR Therapeutics for the treatment of cystic fibrosis (CF). The molecule, administered via inhalation, is designed to repair the cystic fibrosis transmembrane (CFTR) protein at the RNA level in cystic fibrosis (CF) patients who carry the F508del mutation. F508del is the most common mutation, affecting more than 70 percent of CF patients.

How QR-010 works

CFTR proteins transport charged ions across cell membranes. The transport of chloride ions has implications in the movement of water with tissues, allowing the formation of thin mucus that protects and lubricates, among others, the reproductive system, organs (e.g., lungs), and tissues.

CF patients have defective CFTR proteins that are produced when a mutation occurs. The most common of these mutations is F508del, where an amino acid is deleted in the 508 position of the protein. As a result, the passage of water and charged ions through the cell membrane is compromised, resulting in the production of thick mucus.

QR-010’s mechanism of action is to repair the CFTR protein at the RNA level, restoring its function. This experimental therapy is specifically designed to treat only CF patients with the F508del mutation.

History of QR-010

Preclinical data for QR-010 was presented at two scientific conferences in 2015. During the 29th Annual North America Cystic Fibrosis Conference (NACFC) in Phoenix, Arizona, the results showed that QR-010’s diffusion and stability is unlikely to be affected by CF mucus (which was hypothesized to act as a barrier). Additional preclinical data was presented at the European Cystic Fibrosis Conference (ECFS). In vitro and in vivo results demonstrated that QR-010’s diffusion and stability is unaffected by CF mucus.

The first exploratory proof of concept Phase 1 study (NCT02564354) was initiated in 2015, with final data collection concluding in 2016. This open-label study involved 18 CF patients with the F508del mutation and was conducted in the US and Europe. The study aimed at assessing the increase of the CFTR function through the nasal potential difference (NPD). The NPD test measures the chloride transport through the CFTR protein. In October 2016, ProQR announced that the NPD test revealed that CFTR activity is restored after QR-010 administration.

A phase 1b study (NCT02532764) is currently recruiting CF patients homozygous of the F508del mutation, with expected final data collection in 2017. The randomized, double-blind, placebo-controlled study expects to enroll 64 participants from the U.S., Canada, and Europe. The aim is to evaluate the safety, tolerability, and pharmacokinetics of single or multiple ascending doses of QR-010. Some preliminary data from this study showed that QR-010 is safe and well tolerated in single ascending doses. As for multiple ascending doses of QR-010, the results are expected in mid-2017.

QR-010 has been granted fast track designation by the U.S. Food and Drug Administration (FDA), as announced by ProQR.

Next steps for QR-010

As mentioned above, there is Phase 1b (NCT02532764) study currently recruiting CF patients homozygous for the F508del mutation. Results for multiple ascending doses are expected in mid-2017.

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