CellCentric presents early clinical data at ASH: inobrodib (CCS1477), first in class p300/CBP bromodomain inhibitor treating relapsed refractory multiple myeloma

• Inobrodib is an oral drug showing good long-term tolerability at the recommended phase 2 dose as monotherapy
• Objective responses have been observed in heavily pre-treated relapsed / refractory multiple myeloma patients
• Inobrodib is also being evaluated in combination with pomalidomide/dexamethasone, with clear responses seen in first cycle of dosing

CAMBRIDGE, England, Dec. 12, 2022 /PRNewswire/ -- CellCentric, a privately owned, clinical stage biotechnology company pioneering small molecule inhibition of p300/CBP to treat cancer, today announces clinical data for the first time at the 64^th American Society of Haematology (ASH) Annual Meeting, New Orleans.

To date, 26 patients with relapsed/refractory multiple myeloma (RRMM) have been treated with inobrodib as monotherapy, including seven most recently at the recommended phase 2 dose and dose schedule (RP2D). Treatment has been generally well-tolerated with the majority of on-target toxicities being mild or moderate in severity. 

Among the patients treated at the RP2D, six out of seven patients had reduction or stabilisation of serum free light chains. One patient saw an unconfirmed Complete Response (CR), which went on to become a durable confirmed Very Good Partial Response (VGPR); a second patient demonstrated a confirmed Partial Response (PR); and a third currently has an unconfirmed PR (by IMWG response criteria). These three patients remain on treatment after more than eight months.

Dose escalation in combination with pomalidomide and dexamethasone has been initiated in heavily pre-treated RRMM patients. Despite all three initial patients being pomalidomide-refractory, all showed a degree of response after the first cycle of treatment: 1 VGPR, 1 PR and 1 MR (serum M-protein 34% decrease).

Tim Somervaille, the Chief Investigator of Study CCS1477-02, CellCentric's Phase 1 / 2, international haematological malignancy study, and Professor of Haematological Oncology at Cancer Research UK Manchester Institute and The University of Manchester, and Honorary Consultant Haematologist at The Christie NHS Foundation Trust said: "We are excited with these initial clinical results, which show inobrodib has the potential to offer patients with advanced multiple myeloma an additional treatment option. Furthermore, the preclinical data also presented today outlines and supports the hypothesis that targeting p300/CBP with inobrodib represents an entirely novel therapeutic strategy in this disease setting. Taken together, these findings provide clear encouragement for the further clinical development of this first in class drug."

Paul Richardson, Director of Clinical Research and Clinical Program Leader of the Jerome Pippe Myeloma Center and the RJ Corman Professor of Medicine, Harvard Medical School and Dana Farber Cancer Institute added: "This is encouraging early progress in a relapsed and refractory myeloma patient population that has significant unmet medical needs. Demonstrating clear monotherapy activity is important, but so too is seeing promising initial signs of combinability with existing standards of care, which typically serve as backbone agents in this setting." 

Leif Bergsagel, Professor of Medicine for the Mayo Clinic College of Medicine, and a consultant in the Division of Hematology and Medical Oncology, Department of Internal Medicine, at Mayo Clinic, Arizona said: "Inobrodib has an interesting, new mode of action, and importantly is also an oral agent. Ease of use is a key consideration as we look for the widest adoption of new treatments in the community."

Presentation details

Potent Pre-Clinical and Early Phase Clinical Activity of EP300/CBP Bromodomain Inhibitor CCS1477 in Multiple Myeloma

Session Name: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational
Session Date, Time: Saturday, December 10, 2022, 4:00 PM
Room: Ernest N. Morial Convention Center, New Orleans Theater C
Publication Number: 349

About inobrodib:

CellCentric has developed inobrodib from concept through to clinical trials. It is an oral, first in class small molecule inhibitor drug that targets twin cancer gene regulators p300 and CBP. Inhibiting p300/CBP impacts the expression of key cancer drivers including MYC and IRF4 which are particularly important in the progression of certain blood cancers. In addition, inobrodib impacts the androgen receptor pathway. CellCentric has demonstrated that its pioneering drug, inobrodib, has a direct impact on these key oncogenes both pre-clinically and in tumour samples.

Inobrodib is formulated as an oral capsule which, along with its manageable safety profile, allows for administration at home.

As well as testing in heavily pre-treated, relapsed refractory haematological malignancy patients, CellCentric also has a study evaluating inobrodib in solid tumours, including late stage prostate cancer (mCRPC).

About CellCentric:

CellCentric is a research driven and patient-centric clinical stage, private biotechnology company pioneering small molecule inhibition of the twin proteins, p300/CBP. It is focused on the rapid development of inobrodib, a first-in-class small molecule p300/CBP inhibitor, which has the potential to benefit patients with many different cancer indications.

The Company was originally founded with Prof Azim Surani of the Gurdon Institute, University of Cambridge, one of the first people to report on the phenomenon of epigenetics. This is a heritable code separate from DNA, that controls which genes are used or not used. CellCentric has investigated over 50 epigenetic-related targets as new ways to treat disease, and specifically cancer. The company actively pursued multiple drug discovery programmes before prioritising p300/CBP inhibition and inobrodib. An earlier arginine methyl transferase programme was licenced to Takeda Pharmaceuticals.