Preclinical Data on Circle Pharma's CID-078 Featured in Poster Presentation at Advances in Neuroblastoma Research Meeting
'Cyclin A/B-RxL Inhibition as a Novel Therapeutic Strategy in Neuroblastoma'
Dylan M.M. Jongerius et al.
Poster #P010
The poster highlights the work of researchers from the Princess Máxima Center for Pediatric Oncology (Utrecht, the Netherlands), the Hopp Children's Cancer Center Heidelberg (KiTZ) (Heidelberg, Germany), and Circle Pharma, demonstrating the potent anti-tumor activity of CID-078 in preclinical neuroblastoma (NB) models.
CID-078 is a first-in-class oral macrocycle cyclin A/B RxL inhibitor that selectively disrupts RxL-mediated interactions between cyclin A2/B1 and their substrates, a novel mechanism of action that targets cell cycle dysregulation in cancer. In neuroblastoma, where CDK-RB-E2F axis deregulation and oncogenic E2F activity are common, this mechanism is particularly relevant.
Key Findings Presented:
Potent Single agent CID-078 activity was observed across multiple neuroblastoma cell line models.
Mechanism of action studies confirmed induction of DNA damage, G2/M arrest and the activation of the spindle assembly checkpoint (SAC).
Deletion of CDKN2A sensitized cells to CID-078 suggesting CDKN2A status maybe be used as a potential patient stratification strategy.
'A greater understanding of the biology of neuroblastoma, the most common extra-cranial solid tumor diagnosed in children, has shown specific genomic alterations which deregulate the cell cycle leading to E2F activation,' said Michael C. Cox, PharmD, MHSc, BCOP, SVP and head of early development of Circle Pharma. 'Circle's collaboration with these two premier pediatric oncology research institutions has shown again the potential of our macrocycle platform to develop new therapies for historically challenging targets. The exciting CDKN2A deletion biomarker data, as well as the in vitro data in a pediatric tumor with a need for better treatments support our clinical development plans for CID-078.'
The full poster is available here.
About CID-078, Circle Pharma's Cyclin A/B RxL Inhibitor Program
CID-078 is an orally bioavailable macrocycle with dual cyclin A and B RxL inhibitory activity that selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation. In biochemical and cellular studies, Circle Pharma's cyclin A/B RxL inhibitors have been shown to potently and selectively disrupt the protein-to-protein interaction between cyclins A and B and their key substrates and modulators, including E2F (a substrate of cyclin A) and Myt1 (a modulator of cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B RxL inhibitors to cause single-agent tumor regressions in multiple in vivo models. A multi-center phase 1 clinical trial (NCT06577987) is currently enrolling patients.
About Circle Pharma, Inc.
South San Francisco-based Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop therapies for cancer and other serious illnesses. The company's proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies for historically undruggable targets. Circle Pharma's pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. Its lead program, CID-078, a cyclin A/B-RxL inhibitor, is in a Phase 1 clinical trial (NCT06577987) for patients with advanced solid tumors.
To learn more about Circle Pharma, please visit www.circlepharma.com.
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