- Preclinical data findings illustrate power of Cellarity’s discovery platform, which leverages transcriptomics and AI to discover previously unseen biological pathways to create novel cell state-correcting therapeutics
- Oral presentations highlight the promise of Cellarity’s small molecule therapies which may address significant unmet needs for people living with SCD and myelofibrosis
SOMERVILLE, Mass.–(BUSINESS WIRE)–Cellarity, a clinical-stage biotechnology company developing Cell State-Correcting therapies through integrated multi-omics and AI modeling, today announced the presentation of new preclinical data on investigational programs for sickle cell disease (SCD) and myelofibrosis (MF) during the American Society of Hematology (ASH) Annual Meeting.
Cellarity has created a novel approach to drug discovery that focuses on understanding the holistic cell state. The Company’s advanced platform leverages high-dimensional transcriptomics and AI predictive algorithms to discover new biological pathways and to create novel, oral therapeutics that can effectively and safely switch disease mechanisms to healthy cell function, termed as “Cell State-Correcting.” This has resulted in a growing pipeline of differentiated drug candidates, with the first now in clinical development for sickle cell disease.
“Cellarity’s novel platform is fueling meaningful progress, enabling us to explore a broad set of indications across several therapeutic areas. We are advancing our lead asset in sickle cell disease, CLY-124, currently in phase 1 clinical development, while also progressing a second hematology program focused on myelofibrosis in the preclinical stage,” said Ted Myles, Chief Executive Officer of Cellarity. “Together, these efforts reinforce the strength of our platform approach and commitment to delivering highly innovative, novel therapies to patients.”
“The presentations at ASH underscore the power of Cellarity’s novel pipeline of potentially transformative programs in hematology, addressing significant unmet medical need in sickle cell disease and myelofibrosis. CLY-124 has the potential to transform the standard of care in sickle cell disease, as we believe it may induce fetal hemoglobin through a pathway that avoids cytotoxicity that limits other approaches,” said Cameron Trenor, M.D., Chief Medical Officer of Cellarity. “In myelofibrosis, we have identified new candidates that are highly selective in targeting pathways implicated in mutant JAK2 signaling, which may result in the avoidance of anemia that is a common side effect associated with other therapies.”
CLY-124: A first-in-class, oral globin-switching therapy for sickle cell disease
SCD is a devastating inherited disease involving sickle-shaped red blood cells that block blood vessels. Research has demonstrated that increasing fetal hemoglobin (HbF) reduces vaso-occlusive crises (VOCs), pain and organ damage, yet most compounds that increase HbF are limited by cytotoxicity and highly variable patient response. Using its integrated discovery platform, Cellarity evaluated hemoglobin regulation through erythropoiesis to predict chemical compounds that could enrich fetal hemoglobin, identifying high levels of HbF induction associated with neddylation inhibition. This led to the identification of Defective in Cullin Neddylation 1 (DCN1) – a previously unexplored target for globin gene switching. Knockout of DCN1 in vitro led to increased expression of gamma globin genes (HBG1/2) and a higher ratio of fetal vs total globin gene expression with no evidence of cytotoxicity, illustrating a potentially safer globin-switching mechanism.
CLY-124 is being developed as a potent DCN1 inhibitor with optimized pharmacology and pharmacokinetic properties. Preclinical evaluation of CLY-124 demonstrated superiority to hydroxyurea in both fetal hemoglobin protein and globin gene ratios (HBG1/2 over total beta-like globin transcripts), approaching levels reported for recent gene therapy programs. Further, pre-clinical combination studies demonstrated robust synergistic effects when combining CLY-124 with hydroxyurea and with no dose-limiting toxicities. CLY-124 is currently progressing through a phase 1 dose escalating study in healthy volunteers and adults with sickle cell disease.
Selective targeting of mutant JAK2 to address myelofibrosis
Myelofibrosis is a blood cancer caused by mutated gene called JAK2V617F (JAK2) in stem cells within the bone marrow, causing fibrosis, inflammation, and dysfunctional blood cells that lead to anemia, enlargement of the spleen and eventual bone marrow failure. Current JAK2 inhibitor therapies like ruxolitinib manage disease symptoms but are limited by dose because they inhibit both healthy and mutant JAK2 signaling resulting in cytopenias.
Cellarity leveraged high-dimensional transcriptomics from patient samples to map gene signatures uniquely associated with JAK2-mutant hematopoietic stem cells. Through its AI-powered, transcriptomic-driven discovery platform and iPSC (induced pluripotent stem cell)-based disease models, the company identified a novel, druggable biological target and small molecule interventions that selectively suppress the JAK2-mutant clone while sparing normal hematopoiesis.
About Cellarity
Founded by Flagship Pioneering in 2019, 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.
Contacts
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