Announcement • May 20
Quince Therapeutics Announces Clinically Meaningful Improvements Across Functional, Hemodynamic and Biomarker Measures in Phase 2 Study in PAH and PH-ILD
Quince Therapeutics, Inc. announced Phase 2a data evaluating LAM-001, an inhaled formulation of rapamycin (mTOR inhibitor), in patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD), presented at the American Thoracic Society (ATS) conference in Orlando. The Company recently acquired LAM-001 through its previously announced acquisition of Orphai Therapeutics, Inc., a clinical-stage biotechnology company developing LAM-001 to treat rare pulmonary diseases. The Phase 2a study was a 24-week, open-label trial conducted across four clinical sites evaluating LAM-001 as an add-on therapy to standard of care (SOC) in 10 adult patients with PAH and PH-ILD who remained symptomatic despite background therapy. Primary endpoints included change from baseline in peak oxygen uptake (VO2 max) at Week 24, safety and tolerability. Secondary endpoints included pulmonary vascular resistance (PVR), six-minute walk distance (6MWD) and change in functional class, with change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) assessed as an exploratory endpoint. Treatment with LAM-001 was associated with improvement or stabilization from baseline across multiple clinically relevant measures, including 6MWD, PVR, NT-proBNP and forced vital capacity (FVC), supporting potential benefit across exercise capacity, pulmonary hemodynamics, cardiac stress and lung function. Improvements in 6MWD, a clinically meaningful endpoint commonly used in pulmonary hypertension clinical trials and regulatory submissions, were observed alongside favorable changes in hemodynamic and biomarker measures. All evaluable patients also transitioned from Functional Class III to Functional Class II by Week 24. In addition, two patients transitioned to Functional Class I at 16- and 52-week evaluations. LAM-001 was generally well tolerated in patients receiving background standard-of-care therapy. A total of 6 patients were evaluable at the 24-week endpoint, of which 4 were PH-ILD patients. All 4 PH-ILD patients were receiving stable doses of treprostinil therapy before and throughout the study. LAM-001 Phase 2a PH Efficacy: Evaluable Population N=6, PH-ILD Subgroup N=4, ?6MWD (m) +81.3, +67.4; ? VO2 Max (Predicted) +5.4%, +6.7%; % ? PVR (exercise) -25.5%, 35.3%; % ? PVR (supine) 28.1%, -33.9%; % ? NT-proBNP -29.0%, -28.8%; ? FVC (% Predicted) +4.8%, +1.8%. 6MWD = six-minute walk distance; VO2 Max = peak oxygen uptake; PVR = pulmonary vascular resistance; NT-proBNP = N-terminal pro-B-type natriuretic peptide; FVC = forced vital capacity; % predicted compares a patient’s value to expected normal values based on demographic characteristics. LAM-001 is a proprietary, investigational, once-daily inhaled formulation of sirolimus, also known as rapamycin. LAM-001’s potential as a disease-modifying agent in pulmonary hypertension stems from its ability to inhibit mTOR-mediated pulmonary arterial smooth muscle cell proliferation. The mTOR pathway has been shown to be activated in the pulmonary arterial smooth muscle cells of patients with pulmonary hypertension, and mTOR inhibition with rapamycin has been shown to reverse smooth muscle cell hyperproliferation and attenuate pulmonary vascular remodeling and cardiopulmonary dysfunction in multiple nonclinical models. Additionally, mTOR signaling promotes fibroblast activation, myofibroblast differentiation, and extracellular matrix deposition in injured or inflamed lung tissue, and mTOR inhibition has been shown to exert direct anti-fibrotic activity, reducing collagen accumulation, suppressing profibrotic cytokine signaling, and attenuating parenchymal fibrosis. These effects are particularly relevant in pulmonary hypertension associated with interstitial lung disease (PH-ILD), where vascular remodeling and progressive fibrosis evolve in parallel and amplify pulmonary vascular load. LAM-001 is designed to enhance pulmonary delivery and reduce systemic exposure, offering a promising potential disease-modifying therapy for pulmonary disease. LAM-001 is currently being studied in multiple indications including pulmonary hypertension associated with interstitial lung disease (PH-ILD), a serious and progressive condition affecting an estimated ~86,000 patients in the U.S. and ~120,000 in Europe. Based on compelling Phase 2a data presented at the American Thoracic Society (ATS) in May 2026, the company is advancing LAM-001 into a Phase 2b trial in PH-ILD, with initiation planned for mid-2026 and data anticipated in the first quarter of 2028. LAM-001 is also being evaluated in a Phase 2 study in bronchiolitis obliterans syndrome (BOS), a serious complication following lung transplantation affecting an estimated ~17,000 patients in the U.S. and ~11,000 in Europe, with data anticipated in the first quarter of 2027. In late 2026, the company also plans to initiate a Phase 2 study of LAM-001 in sarcoidosis-associated pulmonary hypertension (SAPH), a severe complication of sarcoidosis with no approved therapy affecting an estimated ~60,000 patients in the U.S. and Europe. The Phase 2a study (NCT05798923) was a 10-patient, multicenter, open-label trial evaluating the safety, tolerability and efficacy of LAM-001 as an add-on therapy to standard of care (SOC) in adult patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD) who remained symptomatic despite background therapy. The 24-week study was conducted across four clinical sites in the United States. Primary endpoints included change in peak oxygen uptake (VO2 max) from baseline to Week 24 as well as safety and tolerability. Secondary endpoints included change in pulmonary vascular resistance (PVR), six-minute walk distance (6MWD) and functional class assessments. Exploratory endpoints included change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and forced vital capacity (FVC).
