Proteostasis Therapeutics Inc has been invited to join the HIT-CF Europe, a pan European strategic initiative which seeks to validate a personalized therapy approach for cystic fibrosis (CF) patients with extremely rare genetic mutations.

HIT-CF is a consortium of researchers, doctors, pharmaceutical companies and patient representatives, which aims to provide better treatment for people with CF. The project collects tissue samples from CF patients with diverse genetic profiles and develops patient-derived organoids, cell cultures that are genetically similar to the organ from which they are derived. The organoids are profiled in vitro via their response to drug candidates from the participating pharmaceutical companies. Based on the functional response, patients may be invited to participate in clinical trials with the investigational drugs to validate the ability of the in vitro response to predict clinical benefit. This project is fully funded by a €6.7M award from the Horizon 2020 EU funding program.

Unlike HBE (human bronchial epithelial) cells, which are currently derived from lungs that have been removed from patients, organoids can be more easily derived from a minimally invasive biopsy sample from any patient and used in experimental assays. Organoids can provide valuable insights on the donors including their likelihood of achieving improvements in pulmonary function and reductions in sweat chloride concentration with CFTR modulators based on the in vitro response to those drugs.  Additionally, HIT CF will explore novel regulatory pathways with the European Medicines Agency (EMA) to facilitate patient access to CFTR modulators based on organoid response.

“The ultimate goal of HIT-CF Europe is to develop a path for access to therapies for individual patients or patient groups who show a positive response to the therapy in an organoid test and pave the way for personalized medicine,” said Prof. Dr. C.K. Van der Ent, Program Leader of the HIT-CF consortium.  “We are thrilled to welcome Proteostasis to our consortium. With PTI’s three novel CFTR modulators in advanced clinical trials and exciting early results in the organoid system, we are able to expand testing of the potential therapeutic options in the in vitro system and clinical trials. Through the European Cystic Fibrosis Society (ECFS) networks, which can access 34 clinical research centers across 12 countries, we have already collected biopsies from CF patients and are looking forward to expanding the biobank with samples from more than 500 patients across Europe.”

“We are honored to be selected to participate in the HIT-CF Europe consortium and join forces with key thought leaders to explore the potential of a personalized medicine approach as a possible new frontier for CF therapy,” said Meenu Chhabra, President and Chief Executive Officer of Proteostasis. “With over 2,000 mutations in the CFTR gene identified today, the current “one pill for all” approach is limited in its ability to reach all people with CF who might benefit from disease modifying CFTR modulators. The biology of CF tells us that the CFTR genotype is only one of the many factors that impact the disease phenotype and response to therapy. It is our responsibility to explore new drug development and access avenues that bridge the existing gap,” said Ms. Chhabra.