Initiation follows successful IND clearance based on preclinical data package indicating robust increase in fetal hemoglobin with no cytotoxicity

Novel Globin-Switching mechanism derived from Cellarity's AI-powered transcriptomic discovery platform

SOMERVILLE, Mass., June 26, 2025 /PRNewswire/ -- Cellarity, a biotechnology company developing Cell State-Correcting therapies through integrated multi-omics and AI modeling, today announced that the first subject has been dosed in a Phase 1 clinical trial of CLY-124, a first-in-class Globin-Switching oral medicine designed to treat sickle cell disease (SCD). This follows the Company's successful clearance of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA).

"Initiation of our first-in-human clinical study for CLY-124 represents the delivery of our first clinical asset from our platform with the potential for transformative improvement in care for individuals suffering from sickle cell disease. 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. "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."

SCD is an inherited, devastating disease involving "sickle-shaped" red blood cells that block blood vessels. The disease affects millions of people worldwide, causing chronic and progressive inflammation, pain crises and multi-organ damage. Reactivation of fetal hemoglobin (HbF) has been shown to reduce the disease burden (every 1% increase in HbF leads to 4-6% reduction in pain crisis rates, and prior studies have indicated 20% HbF could effectively resolve disease symptoms when achieved pan-cellularly). Standard of care therapy today induces HbF to improve disease symptoms yet carries dose-limiting cytotoxicity. Hence, novel solutions are warranted that can provide greater efficacy with improved tolerability, ideally in broadly accessible oral formats. 

CLY-124 is an oral therapeutic designed to treat SCD by increasing HbF via a non-cytotoxic mechanism of action. It was created from Cellarity's proprietary drug discovery platform, through which single-cell transcriptomics mapping and AI modeling revealed an undiscovered target controlling the Globin-Switching mechanism. Unlike traditional phenotypic screening approaches, Cellarity conducted a comprehensive assessment of single-cell transcriptomics throughout red blood cell production. This dataset included novel transcriptional signatures predictive of HbF regulation and production, which enabled a precision approach to designing chemistry to influence HbF regulation. CLY-124 inhibits post-translational modification of an upstream protein complex distinct from other approaches that bind DNA or target transcription factors directly. The resulting profile of CLY-124 aims to deliver a highly potent clinical benefit in an oral format with a differentiated mechanism of action and safety profile. In preclinical studies using clinically-translatable human cell models, CLY-124 increased fetal hemoglobin above 20%, with no evidence of cytotoxicity.

The Phase 1 global trial of CLY-124 will assess its safety, tolerability and pharmacokinetic profile initially in healthy volunteers and then among individuals with sickle cell disease. The trial will offer important insights into HbF production, first in healthy volunteers and rapidly followed by patients with sickle cell disease.

"This milestone marks a seminal transition for Cellarity. Following more than six years of cross-functional collaboration among the brightest minds in AI/ML, computational biology, biology and chemistry, we are now a clinical-stage company. Importantly, 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. Our unique approach to drug discovery is producing therapies that have the potential to shift the treatment paradigm for a range of complex diseases with persistent unmet need, including sickle cell disease, myelofibrosis and several immune disorders," said Ted Myles, Cellarity's Chief Executive Officer. "As we begin our first clinical study, we look forward to collaborating with scientific and clinical partners as well as the SCD community of families, caregivers and advocates as we aim to elevate the standard of care for people living with this disease."

About Cellarity

Cellarity is pioneering a fundamentally new approach to drug discovery that corrects whole cell-state dysfunction to solve complex diseases. The Company's proprietary drug discovery platform leverages advanced transcriptomics to comprehensively understand gene networks and applies the power of dynamic AI modeling to predict and design oral Cell State-Correcting therapeutics that can precisely regulate genetic switch mechanisms to restore proper cell function. The Company's lead asset, CLY-124, is designed to treat sickle cell disease through a novel Globin-Switching mechanism and is under evaluation in a Phase 1 clinical study. Additional candidates designed by the platform are advancing for indications in hematology and immunology, and Cellarity has an active collaboration with Novo Nordisk targeting metabolic dysfunction-associated steatohepatitis (MASH). For more information, visit www.cellarity.com.

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