Quince Therapeutics Reports Positive Phase 2a Results for LAM-001 in Pulmonary Hypertension
核心洞察
Quince Therapeutics announced positive Phase 2a results for LAM-001, an inhaled rapamycin formulation, showing clinically meaningful improvements in patients with pulmonary hypertension associated with interstitial lung disease (搜索).
The 24-week study demonstrated a 67.4-meter improvement in six-minute walk distance and a 33.9% reduction in pulmonary vascular resistance in PH-ILD patients receiving LAM-001 as add-on therapy.
Based on these encouraging results, the company plans to initiate a Phase 2b trial in PH-ILD in mid-2026, with topline data expected in the first quarter of 2028.
Quince Therapeutics announced positive Phase 2a results for LAM-001, an investigational inhaled formulation of rapamycin, demonstrating clinically meaningful improvements across multiple measures in patients with pulmonary arterial hypertension (搜索) (PAH) and pulmonary hypertension associated with interstitial lung disease (搜索) (PH-ILD). The data were presented at the American Thoracic Society conference in Orlando.
Study Results Show Broad Clinical Benefits
The 24-week, open-label trial evaluated LAM-001 as an add-on therapy to standard of care in 10 adult patients with PAH and PH-ILD who remained symptomatic despite background therapy. Among the four evaluable PH-ILD patients, treatment with LAM-001 demonstrated a 67.4-meter improvement in six-minute walk distance (6MWD) and a 33.9% reduction in pulmonary vascular resistance (PVR) at 24 weeks.
Additional improvements were observed across multiple clinical measures. The PH-ILD subgroup showed a 6.7% increase in peak oxygen uptake (VO2 max), a 28.8% reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP), and a 1.8% improvement in forced vital capacity. All evaluable patients transitioned from Functional Class III to Functional Class II by Week 24, with two patients achieving Functional Class I at later evaluations.
"What is particularly notable in these early data is the consistency of improvement observed across several important markers of disease burden, including exercise capacity, pulmonary vascular resistance, cardiac stress biomarkers and lung function," said Aaron B. Waxman, M.D., Ph.D., Director of the Pulmonary Vascular Disease Program at Brigham and Women's Hospital and Associate Professor of Medicine at Harvard Medical School. "Improvements in measures such as 6MWD and PVR are especially encouraging given their clinical relevance in pulmonary hypertension and may suggest broader effects on cardiopulmonary physiology."
Mechanism of Action Targets Disease Pathophysiology
LAM-001 is a proprietary, once-daily inhaled formulation of sirolimus designed to inhibit mTOR (搜索)-mediated pulmonary arterial smooth muscle cell proliferation. The mTOR pathway has been shown to be activated in pulmonary arterial smooth muscle cells of patients with pulmonary hypertension, and mTOR inhibition with rapamycin has demonstrated the ability to reverse smooth muscle cell hyperproliferation and attenuate pulmonary vascular remodeling in nonclinical models.
The drug's anti-fibrotic properties are particularly relevant for PH-ILD patients. mTOR (搜索) signaling promotes fibroblast activation, myofibroblast differentiation, and extracellular matrix deposition in injured lung tissue. mTOR inhibition has shown direct anti-fibrotic activity, reducing collagen accumulation and suppressing profibrotic cytokine signaling. These dual effects address both vascular remodeling and progressive fibrosis that evolve in parallel in PH-ILD.
Safety Profile and Development Timeline
LAM-001 was generally well tolerated in patients receiving background standard-of-care therapy. All four PH-ILD patients in the evaluable population were receiving stable doses of treprostinil therapy before and throughout the study period.
Based on these Phase 2a results, Quince Therapeutics plans to advance LAM-001 into a Phase 2b trial in PH-ILD, with initiation planned for mid-2026 and topline data anticipated in the first quarter of 2028. The company is also evaluating LAM-001 in a Phase 2 study for bronchiolitis obliterans syndrome (搜索), with data expected in the first quarter of 2027, and plans to initiate a Phase 2 study in sarcoidosis-associated pulmonary hypertension (搜索) in late 2026.
Addressing Significant Unmet Medical Need
PH-ILD affects an estimated 86,000 patients in the United States and 120,000 in Europe. According to Dr. Waxman, "Patients with PH-ILD continue to face substantial limitations in daily functioning and a high risk of clinical deterioration despite currently available therapies." The condition represents an area where meaningful therapeutic advances remain urgently needed.
The Phase 2a study (NCT05798923) was conducted across four clinical sites in the United States, with primary endpoints including change in peak oxygen uptake from baseline to Week 24, safety, and tolerability. Secondary endpoints included changes in pulmonary vascular resistance, six-minute walk distance, and functional class assessments.