CellCentric Ltd: Pioneering Epigenetic Inhibition for Cancer Therapy
CellCentric Ltd. is a UK-based, clinical-stage biopharmaceutical company that operates at the intersection of epigenetics and oncology, specializing in the discovery and development of novel small molecule inhibitors to treat specific cancers. Founded in 2003/2004, the company has its core foundation in the science and understanding of cell fate control mechanisms and has strategically focused its development efforts on a first-in-class therapeutic candidate. The company???s mission is to rapidly and effectively develop its lead drug for the benefit of patients suffering from multiple myeloma and other cancer types.
Continue…Core Business and Mechanism of Action
CellCentric???s primary focus and competitive advantage lie in its pioneering work on the inhibition of the twin proteins p300 and CBP (EP300/CBP). These proteins are Histone Acetyltransferases (HATs) that act as transcriptional co-activation factors for genes involved in tumor progression. The company's therapeutic strategy targets the bromodomain of p300/CBP, a binding pocket, with a highly selective small molecule.
The mechanism of action involves the small molecule displacing, rather than degrading, both p300 and CBP from super enhancer sites to other parts of the chromatin. This displacement reduces the expression of critical oncogenic drivers, such as MYC and IRF4, which are implicated in the proliferation and survival of cancer cells.
Beyond its direct impact on cancer cell growth, the p300/CBP bromodomain inhibition has also demonstrated the potential to modulate the tumor microenvironment (TME). Specifically, studies have shown that the inhibition can:
- Reduce PD-L1 expression: By reducing the transcription of PD-L1, including exosomal PD-L1, the treatment may overcome mechanisms of resistance to PD-L1 blockade therapy.
- Modulate Immunosuppression: Treatment can lead to a marked reduction of myeloid-derived suppressor cells (MDSCs) in the TME by inhibiting key cytokines, thereby creating a more favorable environment for tumor-infiltrating lymphocytes and enhancing the efficacy of immune checkpoint blockade (ICB) therapy.
Products and Pipeline
The company's lead and principal product is the investigational drug inobrodib (formerly known as CCS1477).
Inobrodib (First-in-Class p300/CBP Inhibitor)
* Drug Class: First-in-class small molecule p300/CBP bromodomain inhibitor. The World Health Organisation has confirmed "inobrodib" as a new International Non-proprietary Name (INN), with the "-brodib" suffix representing the novel drug class of p300/CBP bromodomain inhibitors.
* Administration: It is an orally bioavailable drug, which is a key patient preference and aims to reduce the burden on the healthcare system by allowing for community-setting administration.
* Therapeutic Focus and Clinical Stage: Inobrodib is a clinical-stage asset that has completed Phase I and is transitioning into Phase II clinical trials across multiple indications.
* Primary Indication: Multiple Myeloma (MM). This is the indication CellCentric currently sees as offering the clearest path for clinical and commercial impact. It is being evaluated as monotherapy and in combination, such as InoPd (inobrodib in combination with pomalidomide and dexamethasone), for patients with relapsed or refractory multiple myeloma, including those who are penta-refractory and post-BCMA therapy.
* Other Potential Indications: The drug's mechanism suggests therapeutic utility in other p300/CBP-regulated cancers, including castration-resistant prostate cancer (mCRPC), Acute Myeloid Leukemia (AML), lymphomas, and other solid tumors or tumors driven by specific genomic alterations.
Services and Partnerships
While its primary focus is on the development of inobrodib, CellCentric's operational activities are characterized by deep scientific collaboration and historical business development:
- Knowledge and Target Discovery: The company was initially considered a "knowledge company" that leveraged its foundational work in epigenetics to aid other groups. Its competitive advantage is partly derived from its strong relationships with over 30 leading research centers globally, which provide privileged information from target discovery to clinical data.
- Business Development/Licensing: CellCentric has a history of successful business development deals, including the development, partnering, and subsequent licensing of an arginine methyltransferase drug discovery program to Takeda Pharmaceuticals.
- Research & Clinical Collaboration: The company operates internationally and engages with patient-focused organizations and clinical collaborators to ensure its drug development aligns with the needs and priorities of people living with cancer.
