Blueprint Medicines Corporation announced PIONEER trial results highlighting the long-term efficacy and safety of AYVAKIT (avapritinib) in patients with indolent systemic mastocytosis (ISM), as well as foundational preclinical data for BLU-808, an investigational highly selective and potent oral inhibitor of wild-type KIT. Blueprint Medicines will report a total of nine data presentations, including two oral presentations, reflecting the company's long-standing commitment to transform care for patients living with mast cell disorders. The datasets are being reported at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting being held February 23-26 in Washington, D.C. AYVAKIT: Durable Symptom Impact and Well-Tolerated Safety Profile in Patients with ISM Long-term data from the PIONEER trial show that AYVAKIT led to robust improvements across all symptom domains (skin, gastrointestinal, neurocognitive) at 24 weeks, with sustained benefits through 48 weeks.

In addition, patients treated with placebo during the blinded portion of the trial had rapid and durable symptom improvements upon cross-over to AYVAKIT. Symptom improvements were assessed by the validated Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF). After 48 weeks of treatment with AYVAKIT, 35 percent of patients reduced or discontinued use of best supportive care medicines.

As of the updated data cut, the last patient treated with AYVAKIT in the blinded portion of the trial reached the 48-week timepoint. With a median patient follow-up of 18 months, the safety profile of AYVAKIT was consistent with previously reported results from the 6-month placebo-controlled portion of the trial, with no new safety signals observed. Most adverse events (AEs) were mild or moderate (Grade 1-2), and the most common treatment-related AEs (=5 percent) were peripheral edema, headache, periorbital edema and nausea.

The rate of treatment-related AEs leading to discontinuation remained low (3 percent). BLU-808: An Investigational, Potent and Selective Wild-type KIT Inhibitor for Chronic Urticaria and Other Mast Cell Diseases Mast cells play a critical frontline role in a healthy immune response; activation through KIT and other receptors leads to degranulation and release of downstream effectors that mediate inflammation. However, when mast cells are dysregulated, they are drivers of multiple common allergic and inflammatory diseases such as chronic urticaria, for which wild-type KIT is a clinically validated therapeutic target.

BLU-808 is an investigational, highly selective and potent oral wild-type KIT inhibitor designed to enable tolerability and flexibility to tailor treatment based on disease severity and patient needs. In foundational preclinical data reported at AAAAI, BLU-808 demonstrated a best-in-class selectivity and potency profile in vitro. In multiple in vivo studies, BLU-808 treatment led to dose-dependent inhibition and depletion of mast cells.

In addition, BLU-808 improved lung function in an ovalbumin-induced asthma model. Based on these data, Blueprint Medicines expects to submit an investigational new drug application for BLU-808 in the second quarter of 2024, and subsequently plans to initiate a Phase 1 study in healthy volunteers. The initial development focus for BLU-808 will be in chronic urticaria.