Eloxx Pharmaceuticals will explore the potential of its lead investigational drug candidate, ELX-02, as a treatment for patients with cystic fibrosis (CF) caused by rare nonsense genetic mutations, in new trials integrated in the European HIT-CF project.
“We are extremely excited to be participating in the HIT-CF research project which has the potential to lead to treatment options for the many CF patients based on their functional responses in the lab,” Gregory Williams, PhD, chief operating officer at Eloxx Pharmaceuticals, said in a press release.
A European Union-funded consortium agreement, the HIT-CF project was designed to test investigational CF therapies first in patient-derived mini-organoids (cell cultures that are grown in the lab and look similar to the organ from which they are derived) and, based on their responsiveness, advance the therapies for clinical assessment in selected smaller groups of patients.
The project aims to help predict the CF patient’s clinical response in a controlled study using a preclinical model, and is coordinated by Kors van der Ent, MD, from the University Medical Center Utrecht, in the Netherlands. The strategy is expected to improve the outcome of clinical studies, and expedite the development of potentially effective new therapies for patients with rare genetic variants.
This integrative and personalized strategy to facilitate the translation between preclinical and clinical data can be extended to other human genetic disorders other than CF.
“This important project will now include CF patients with rare nonsense mutations, often representing the most severe and underserved phenotypes (disease presentation),” Williams said. “We believe the results of this project may extend the use of organoid response data to the regulatory process for drug approval or label expansion as well as for treatment/reimbursement decision making.”
First, researchers will collect stem cells from the patient’s own intestines to “create” the organoids. These preclinical models will then be distributed to laboratories in the Netherlands (Utrecht), Belgium (Leuven), and Portugal (Lisboa), where they will be used to test the efficacy of experimental therapies.
Based on their cells’ responsiveness to treatment, patients will be selected and invited to participate in clinical trials being conducted at 43 CF centers of the ECFS Clinical Trial Network (ECFS-CTN).
ELX-02 is a small molecule that was designed to target nonsense genetic mutations and restore the activity of previously nonfunctional proteins that cause CF and cystinosis. This investigational compound has received orphan medicine status by the European Medicines Agency (EMA) for the treatment of CF, mucopolysaccharidosis type I (MPS I), as well as orphan drug designation by the U.S. Food and Drug Administration (FDA) for cystinosis, MPS I, and Rett Syndrome.
Eloxx is planning to launch a Phase 2 trial after completing an ongoing Phase 1 multiple ascending-dose study in healthy volunteers (NCT03309605). The new trial will evaluate the safety and tolerability of ELX-02 in CF patients carrying the G542X mutation.
The Phase 2 trial is pending approval by the Belgium regulatory agency and pre-Investigational New Drug discussions with the FDA.