San Francisco-based Quince Therapeutics Inc., revealed that its pivotal Phase III NEAT clinical trial evaluating dexamethasone sodium phosphate encapsulated in autologous erythrocytes (eDSP) in ataxia-telangiectasia (A-T) did not meet its primary or key secondary endpoints, and the company will discontinue clinical development of the program. eDSP, a novel drug-delivery form of dexamethasone designed to mitigate corticosteroid toxicity via encapsulation in a patient’s own red blood cells, had been positioned as a potential treatment for the rare, inherited neurodegenerative disorder. Quince said eDSP was generally well tolerated but failed to achieve statistically significant clinical benefit compared with placebo in the NEAT study.

Trial outcomes and development decision

Under the NEAT trial’s international, multicenter, randomized, double-blind, placebo-controlled design, change from baseline to the last efficacy visit at six months was evaluated using the Rescored modified International Cooperative Ataxia Rating Scale (RmICARS). Neither the primary endpoint nor the company’s key secondary endpoint, improvement in Clinical Global Impression of Severity (CGI-S), achieved statistical significance versus placebo. eDSP’s safety profile was consistent with prior observations, with no clinically meaningful safety concerns identified. Formation of pruritis and pyrexia were among the more commonly reported adverse events in the active arm. In response to the negative findings, Quince said it will cease further development of eDSP and focus on preserving cash and evaluating options for the company moving forward.

eDSP leverages Quince’s proprietary Autologous Intracellular Drug Encapsulation (AIDE) technology platform, which encapsulates active agents within a patient’s red blood cells to facilitate sustained delivery while potentially reducing systemic toxicities. The rationale for A-T, a condition caused by mutations in the ATM gene and characterized by progressive neurologic deterioration, immunodeficiency, and high morbidity, was to harness controlled corticosteroid exposure to modulate disease progression without conventional steroid-associated adverse effects. Prior to topline disclosure, the NEAT study enrolled 105 participants, including 83 in the primary analysis population aged six to nine years and 22 aged 10 years and older.

Quince’s pipeline strategy had centered on advancing eDSP as its lead asset and a first-to-market therapy for A-T, a rare neurodegenerative disorder with no currently approved treatments. The failure of NEAT effectively eliminates its most advanced program. The company said it will preserve cash, explore strategic alternatives, and reallocate resources as part of a business plan reset.

Although eDSP did not achieve its efficacy goals, other agents in A-T and related rare neurodegenerative landscapes are advancing, underscoring ongoing interest in the space: Levacetylleucine (Aqneursa) – IntraBio’s small molecule reported statistically significant improvements in ataxia symptoms versus placebo in a Phase III study for A-T and is being positioned for regulatory submissions across multiple regions.