P300/CBP is an emerging target offering a new path to treat specific cancers. CCS1477, developed by CellCentric, is a small molecule inhibitor of the twin regulator proteins, and formulated as an oral capsule. CCS1477, a first-in-class compound is in parallel strands of clinical trials to treat endocrine resistant prostate cancer, haematological malignancies and targeted tumours (with particular mutations or molecular drivers). These are all significant clinical unmet needs. Following Phase 1b dose escalation and schedule setting conducted at 16 centres in the UK, CellCentric’s clinical programme is expanding into the US, with the FDA opening an IND for CCS1477 for solid tumours.
CCS1477 is novel drug to treat specific cancers. It is a highly specific inhibitor of the common bromodomain of twin acetyltransferases and gene co-activators p300 and CBP. The compound and target pathway was presented at AACR 2019 as a New Drug on the Horizon, and a summary of pre-clinical and translational data published in Cancer Discovery in January 2021:
Inhibiting p300/CBP impacts the transcription of Myc, a well characterised driver of cancer tumours. It also down regulates both the androgen receptor and its variants, known to be important in the progression of late stage, drug resistant, prostate cancer. P300/CBP inhibition also impacts IRF4, which is important in certain haematological malignancies. CellCentric has initiated clinical trials evaluating CCS1477 as a monotherapy, and in combination with standard of care agents. For prostate cancer, this includes abiraterone and enzalutamide. For haematological malignancies, this will include pomalidomide and azacytidine.
Clinical trials of CCS1477 were initiated originally at The Royal Marsden NHS Foundation Trust, London and The Christie NHS Foundation Trust, Manchester. 16 centres are now active in the UK. The expansion to the US builds on the continued progress that was made despite the challenges of the Covid pandemic, with dose and schedules being finalised across different indications. CellCentric has collaborated with multiple research and clinical centres in the US, including Thomas Jefferson University/Sidney Kimmel Cancer Centre, Philadelphia; Columbia University, New York; and The Mayo Clinic, Phoenix.
CEO, Dr Will West, commented ‘Running clinical trials over the last year has obviously not been easy. The team has done an incredible job in building capacity and delivery over the last 12 months. Expanding now into the US is a key step, building on the strong operational platform already created.’
CellCentric is a clinical development stage biotechnology company focused on a first-in-class p300/CBP bromodomain inhibitor drug, CCS1477, to treat specific cancers. The company investigated over 50 potential epigenetic-related drug targets, before focusing on the twin histone acetyl transferases p300/CBP. An earlier programme, based on an arginine methyltransferase target, was licenced to Takeda Pharmaceuticals.
CellCentric is a privately held business, with Morningside Venture Investments as its lead investor. It is UK based (Cambridge; Manchester; Oxford), with multiple international operations and collaborations.