MON-069 Once-daily Oral Paltusotine In The Treatment Of Patients With Biochemically Uncontrolled Acromegaly: Interim Results Of The PATHFNDR-2 Open-label Extension

Abstract Disclosure: M. Gadelha: Ipsen, Crinetics Pharmaceuticals, Inc., Novo Nordisk, Recordati, Camurus. A. Casagrande: Crinetics Pharmaceuticals, Inc. A. Elenkova: Pfizer, Inc., Novartis Pharmaceuticals, Novo Nordisk, Corcept Therapeutics, Crinetics Pharmaceuticals, Inc., Xeris Pharmaceuticals, Recordati Rare Diseases. C.L. Boguszewski: Crinetics Pharmaceuticals, Inc., Ipsen, Novo Nordisk, Recordati. R.S. Jallad: Crinetics Pharmaceuticals, Inc. B. Hu: Crinetics Pharmaceuticals, Inc.. E. Hubina: None. P.K. Fazeli: Crinetics Pharmaceuticals, Inc., Regeneron Pharmaceuticals, Quest Diagnostics, Corcept, Amryt, Camarus. M. Fleseriu: Amolyt, Camarus, Crinetics Pharmaceuticals, Inc., Debiopharm, Novo Nordisk, Recordati. P.J. Snyder: Crinetics Pharmaceuticals, Inc. C.J. Strasburger: Crinetics Pharmaceuticals, Inc., Amolyt, Novo Nordisk, Pfizer, Inc., Recordati, Sandoz-Hexal. M. Bidlingmaier: Amolyt, Camarus, Chiasma, Crinetics Pharmaceuticals, Inc., IDS, Ionis Pharmaceuticals Inc., Lumos, OPKO, Novo Nordisk, Pfizer, Inc., Roche Pharmaceuticals, Sandoz, Euroimmun. Y. Zhao: None. B. Soares: Crinetics Pharmaceuticals, Inc., Ipsen, Novo Nordisk, Recordati. P.J. Trainer: Crinetics Pharmaceuticals, Inc. R.S. Struthers: Crinetics Pharmaceuticals, Inc. A. Krasner: Crinetics Pharmaceuticals, Inc. B.M. Biller: Crinetics Pharmaceuticals, Inc., Ionis Pharmaceuticals Inc., Amolyt, Amryt, Camarus, Pfizer, Inc., Recordati. Paltusotine is aselective, non-peptide, SST2 receptor agonist in development as a once-dailyoral treatment for patients with acromegaly or carcinoid syndrome. PATHFNDR-2was a randomized, double-blind, placebo-controlled trial (24-week randomizedcontrolled [RC] phase; single-arm, open-label extension [OLE; currentlyongoing]) that evaluated the efficacy and safety of paltusotine in patientswith biochemically uncontrolled acromegaly. The OLE is evaluating the efficacyand safety of longer-term treatment with paltusotine. Of 106 patients whocompleted the RC phase, 103 (97.2%) continued into the OLE (paltusotine in RC,n=51; placebo in RC, n=52). In addition, 11 patients who met eligibilitycriteria for the RC phase and were in the screening process when targetenrollment was reached were directly enrolled in the OLE. At this interimanalysis (data cutoff: September 1, 2024), 88 patients had efficacy data atStudy Week 60 (OLE Week 36; efficacy analysis). The safety analysis includedall 114 enrolled patients. Compared with OLE baseline, mean IGF-I wasmaintained in patients who received paltusotine in the RC (Week 60 mean change,-0.01 xULN; n=40) and decreased in patients who received placebo in the RC (Week26 mean change, -0.63 xULN; n=52; Week 60 mean change, -0.81 xULN; n=39) anddirectly enrolled patients (Week 60 mean change, -0.75 xULN; n=9). Mean AcromegalySymptom Diary score was maintained in paltusotine RC patients (Week 60 meanchange, 0.1; n=39) and decreased in placebo RC patients (Week 60 mean change, -1.8;n=39) and directly enrolled patients (Week 60 mean change, -1.1; n=8). As ofthis analysis, 13 patients (11.4%) had discontinued from the OLE: 9investigator decision, 2 due to AEs, 1 withdrawal by patient, and 1 requiringprohibited medication. Paltusotine was generally well tolerated. In conclusion,IGF-I levels decreased rapidly in patients who had received placebo during theRC phase and patients with elevated IGF-I who were directly enrolled into theOLE, and the previously observed decrease was sustained in patients whocontinued on once-daily oral paltusotine. Paltusotine was well tolerated duringlong-term treatment. Presentation: Monday, July 14, 2025