Quince Therapeutics (NASDAQ:QNCX) outlined development plans for its inhaled sirolimus candidate, LAM-001, across pulmonary hypertension associated with interstitial lung disease, bronchiolitis obliterans syndrome following lung transplant, and sarcoidosis-associated pulmonary hypertension during a virtual key opinion leader event.
Brigette Roberts, the company’s chief corporate affairs officer and board member, said LAM-001 is designed to deliver rapamycin directly to lung tissue through a dry-powder inhaler. The company is administering a 100-microgram daily dose, which Roberts said is one-twentieth of a typical oral dose. She said systemic drug levels have remained below one nanogram per milliliter in human studies, with the goal of limiting systemic exposure and associated side effects.
PH-ILD Program Targets 2028 Data Readout
Aaron Waxman, director of the Pulmonary Vascular Disease Program at Brigham and Women’s Hospital, said PH-ILD is associated with substantial mortality and remains underdiagnosed, in part because clinicians historically had limited treatment options. He said pulmonary hypertension can raise mortality roughly threefold in patients with interstitial lung disease.
Waxman discussed the limitations of systemic pulmonary vasodilators in this population, including the potential to worsen ventilation-perfusion matching and oxygenation. He cited inhaled treprostinil’s INCREASE study as evidence that inhaled delivery can target better-ventilated regions of the lung while reducing some risks associated with systemic vasodilation.
He also reviewed preclinical research supporting inhibition of the mTOR pathway, which is involved in cellular proliferation, inflammatory signaling and fibrosis. However, Waxman noted that the findings discussed from animal models were preclinical and did not establish clinical efficacy.
Paul Yu, director of the Cardiovascular Research Center at Massachusetts General Hospital, presented results from an open-label Phase IIa study of LAM-001 in five Group 1 pulmonary arterial hypertension patients and five PH-ILD patients. All participants had functional Class III disease and were receiving background therapy at enrollment, according to Yu.
Four patients discontinued early for reasons described as unrelated to study drug, including acute coronary syndrome in one participant and vaping-related lung injury in another. Among six patients who completed the study, Yu said investigators observed improvements across several functional, hemodynamic and biomarker measures. He reported a median 60.1-meter increase in six-minute walk distance, a 5% increase in predicted peak oxygen uptake, and reductions in pulmonary vascular resistance and NT-proBNP. All completers improved to at least functional Class II by week 24, with two reaching Class I.
Yu cautioned that the cohort was small and open label. He said the randomized Phase IIb PH-ILD study will evaluate two LAM-001 doses, with pulmonary vascular resistance serving as the primary endpoint.
BOS Study Fully Enrolled
Steve Hays, medical director of the UCSF Advanced Lung Disease and Lung Transplant Program, described bronchiolitis obliterans syndrome, or BOS, as the most common form of chronic lung allograft dysfunction after lung transplantation. He said BOS occurs in roughly 50% of transplant recipients within five years and is a leading cause of death by 10 years after transplant.
BOS is characterized by fibrotic narrowing and obstruction of small airways. Hays said it is diagnosed clinically through persistent declines in forced expiratory volume in one second, or FEV1, after other reversible causes such as infection are excluded. He said median survival after diagnosis is approximately three to five years.
According to Hays, there are no FDA-cleared treatments for BOS. Current approaches can include intensified immunosuppression, treatment of infections, macrolide therapy for a responsive subgroup of patients, extracorporeal photopheresis, and retransplantation in selected cases.
Quince’s investigator-sponsored Phase II study at UCSF is fully enrolled and is comparing 100 micrograms of LAM-001 with placebo over 48 weeks in adults with newly diagnosed BOS. The primary endpoint is change in percent FEV1 over the treatment period. Top-line data are expected in the first quarter of 2027.
Hays said a 5% to 10% difference between treatment and placebo in FEV1 change over 48 weeks would be clinically meaningful. He said the trial requires participants to be on three-drug immunosuppression before enrollment and is evaluating LAM-001 as an add-on therapy.
Beyond the PH-ILD and BOS programs, Roberts said Quince plans to begin a Phase II study in sarcoidosis-associated pulmonary hypertension near the end of the year, with data expected about two years later, or toward the end of 2028.
About Quince Therapeutics (NASDAQ:QNCX)
Quince Therapeutics, Inc is a clinical-stage biotechnology company focused on developing treatments for rare diseases. The company’s research centers on its erythrocyte-derived extracellular vesicle (EEV) platform, which uses patients’ red blood cells to encapsulate and deliver therapeutic compounds.
Quince’s lead investigational product is eDSP, formerly known as EryDex, an autologous red-blood-cell-based formulation of dexamethasone sodium phosphate being developed for ataxia-telangiectasia (A-T).
