Cellarity has achieved a significant milestone in sickle cell disease treatment by dosing the first patient in a Phase 1 clinical trial of CLY-124, a first-in-class oral medicine designed to increase fetal hemoglobin through a novel globin-switching mechanism. The biotechnology company received FDA clearance for its Investigational New Drug application based on preclinical data showing robust fetal hemoglobin increases without cytotoxicity.
Novel AI-Driven Drug Discovery Approach
CLY-124 emerged from Cellarity's proprietary drug discovery platform that combines single-cell transcriptomics mapping with AI modeling to identify previously undiscovered therapeutic targets. Unlike traditional phenotypic screening approaches, the company conducted comprehensive single-cell transcriptomic assessments throughout red blood cell production, revealing novel transcriptional signatures predictive of fetal hemoglobin regulation and production.
"CLY-124 is the first validation of our powerful proprietary discovery platform that has allowed us to see biological pathways and create medicines that conventional discovery efforts could not have achieved," said Ted Myles, Cellarity's Chief Executive Officer.
The drug works by inhibiting post-translational modification of an upstream protein complex, representing a distinct mechanism from other approaches that bind DNA or target transcription factors directly. This precision approach enabled the design of chemistry specifically tailored to influence fetal hemoglobin regulation.
Addressing Critical Unmet Medical Need
Sickle cell disease affects millions of people worldwide, causing chronic and progressive inflammation, pain crises, and multi-organ damage through "sickle-shaped" red blood cells that block blood vessels. Current standard-of-care therapies that induce fetal hemoglobin carry dose-limiting cytotoxicity, creating a significant treatment gap.
The therapeutic potential of fetal hemoglobin reactivation is well-established, with every 1% increase in fetal hemoglobin leading to a 4-6% reduction in pain crisis rates. Prior studies indicate that achieving 20% fetal hemoglobin pan-cellularly could effectively resolve disease symptoms.
"The novel mechanism of CLY-124, which naturally increases fetal hemoglobin through Globin-Switching, could address pain, anemia, and other symptoms to improve organ function and quality of life," said Cameron Trenor, M.D., Cellarity's Chief Medical Officer.
Promising Preclinical Results
In preclinical studies using clinically-translatable human cell models, CLY-124 increased fetal hemoglobin above 20% with no evidence of cytotoxicity. This profile suggests the potential for best-in-class fetal hemoglobin production without the safety limitations of conventional therapies.
The drug's oral formulation offers significant advantages for patient accessibility and compliance, potentially providing a once-daily treatment option for all patients with sickle cell disease.
Phase 1 Trial Design and Objectives
The Phase 1 global trial will assess CLY-124's safety, tolerability, and pharmacokinetic profile initially in healthy volunteers before advancing to individuals with sickle cell disease. The study design will provide important insights into fetal hemoglobin production patterns across both populations.
"Our strong body of preclinical evidence suggests CLY-124 may offer best-in-class fetal hemoglobin production without the cytotoxicity associated with conventional therapies, and importantly, could be accessible to all patients through a once-daily oral pill," Trenor noted.
Platform Validation and Pipeline Expansion
The initiation of CLY-124's clinical development marks Cellarity's transition to a clinical-stage company after more than six years of platform development. The company's Cell State-Correcting approach has generated additional candidates advancing for indications in hematology and immunology, with an active collaboration with Novo Nordisk targeting metabolic dysfunction-associated steatohepatitis.
Cellarity's platform leverages advanced transcriptomics to understand gene networks and applies dynamic AI modeling to predict and design oral therapeutics that can precisely regulate genetic switch mechanisms to restore proper cell function.
