P081 Theratyping – extending the success of highly effective CFTR modulators to rare mutations

Background: elexacaftor/tezacaftor/ivacaftor (ETI) is approved for CF patients with at least one F508del mutation. The concept of “Theratyping”—aligning genotypes based on their in vitro response to CFTR modulators, enabled approval ETI rarer mutations. We report a rare mutation that was responsive both and vivo. Mutation description: Q1100P an ultra-rare mutation, carried by seven Israeli Arab patients; three them are followed our center. Intestinal organoids demonstrated positive two patients. Patients 1,2 - siblings, carrying Q1100P/K163E. Based organoid assay from them, started ETI: patient #1–18 years old, had FEV1 55%, sputum grew Pseudomonas Nocardia. He treated several antibiotics side effects, Creon GI symptoms. Under ETI, improved 74%, LCI declined (16 11) sweat chloride (72 42 mmol/L). younger brother: 17 suffered recurrent pancreatitis multiple admissions. Due low fecal elastase he received Creon. His 75% MSSA. reached 90%, (13.1 7.5 73 64 mmol/L, respectively). Three months after initiation, there were no further admissions pancreatitis. Patient #3: 15-years-old PI. Mutations Q1100P/C225X. 92% sputum. Despite did not start treatment since his considered eligible ETI. Conclusions: described showed restored activity clinical improvement real life. suggest should be this These reported cases support the idea modulators can tried mutations show activity, continued those response.