Inobrodib

UK-based biotech, CellCentric which spun out of Cambridge University has today (December 11) announced new clinical data for the drug at the American Society for Hematology (ASH) in San Diego. The results follow a recent publication in the Cancer Cell journal, which describes the novel mechanism of action of inobrodib, a first in a new class of drug – an oral agent.  The drug disrupts the action of p300/CBP at regulatory elements controlling key cancer genes. Inobrodib impacts the expression of IRF4 and MYC, two potent oncogenes that drive multiple myeloma. The mechanism is clearly differentiated from that of other commonly used drugs, and it has also been proven to be synergistic to agents such as the IMiDs.  As now shown clinically, patients refractory to pomalidomide become responsive to inobrodib combined with pom + dex. “We are pleased that clinical activity of this combination is so encouraging in last-line patients, confirming the potential of this new approach,” said Tomasz Knurowski, chief medical officer at CellCentric. “Further evaluation is underway, but there are clear signs that targeting p300/CBP to treat haematological malignancies, including myeloma, has the potential to address unmet medical need.” The data has been derived from heavily pre-treated patients, who are mostly triple-class refractory (when the disease does not respond to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies), with a median of five lines of prior therapy who have been taking part in a multi-center phase 1/2a clinical ​ trial. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Data were shared at ASH from two combination cohorts at doses of inobrodib at 25mg or 35mg twice daily on a four days on / three days off intermittent schedule, with standard dosing of pom + dex in 28-day cycles. The results showed inobrodib has a manageable safety profile.  All patients demonstrated some signs of clinical activity, with rapid responses - 72% greater than or the same as MR by IMWG criteria in both cohorts and 67% ORR in the 35mg cohort.  A significant number of patients across both dosing cohorts remain on treatment after six months. CellCentric has previously reported initial monotherapy tolerability and efficacy data, at ASH 2022. Emma Searle, consultant haematologist at The Christie NHS Foundation Trust, who has overseen the care of many of the patients on the clinical trial, added: “The results show promising efficacy data in relapsing-remitting multiple myeloma patients who have exhausted standard-of-care therapies, both as a monotherapy and in combination with pom + dex. Further trials continue to refine dosing and expand the cohort.” Multiple myeloma, also known as myeloma, is a type of bone marrow cancer. Bone marrow is the spongy tissue at the center of some bones that produces the body's blood cells. It is called multiple myeloma as the cancer often affects several areas of the body, such as the spine, skull, pelvis and ribs.

CellCentric, a UK-based biotechnology company, announced today (November 22) the publication of the paper and how the work builds on pre-clinical and clinical collaborations, notably with Professor Tim Somervaille of the Cancer Research UK Manchester Institute. The paper, titled, Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies ​ ​, reports on the therapeutic mechanism of inobrodib and relevant clinical results. The paper demonstrates inobrodib’s action as a potent and selective inhibitor of the bromodomains of p300 and CBP and shows how it has a profound impact on the regulatory elements which control expression of key cancer driver genes. Inobrodib induces a significant redistribution of p300/CBP away from sites occupied by oncogenic master transcription factors. This novel approach is distinct from other oral agents such as the IMiD and CELMoD class of drugs.  The data show that this mechanism of action is synergistic with a number of existing developmental agents. Well-tolerated new type of treatment Somervaille said: “We are pleased to share how targeting the bromodomain of p300/CBP can deliver a new way to treat specific blood cancers. The mechanism of action is more targeted than might be anticipated, offering clear potential to be a well-tolerated new type of treatment.” The paper also describes initial data from a phase 1a/2b hematological malignancy clinical trial. Inobrodib can be well tolerated whilst demonstrating potential in treating relapsed refractory multiple myeloma and AML. It is an oral drug, a capsule taken twice daily.  A key patient preference is for treatments that are easy to administer and can be taken in community settings.  This also reduces the overall healthcare burden. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Emma Searle, consultant haematologist at The Christie NHS Foundation Trust, who has overseen the care of many of the patients on the clinical trial, said: “Early clinical data shows promising tolerability, a key factor in treating patients with relapsed, refractory multiple myeloma who have exhausted standard-of-care therapies.  We look forward to sharing efficacy data at ASH in December.” Hematological malignancies Leif Bergsagel, is 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 in Arizona. He said: “This new paper supports that targeting p300/CBP to treat hematological malignancies is showing increasing potential.  It is clearly a distinctly new approach beyond the existing standard of care therapies and others in late-stage development.” CellCentric’s ongoing blood cancer trial ​ involves patients with a range of hematological malignancies, including in relapsed/refractory multiple myeloma. Good safety profile Inobrodib is a new type of treatment for people with cancer. Delivered as an oral capsule, CellCentric says it is easy for patients to take and can be used at home without the need for intensive monitoring. As it has a good safety profile for a drug in this setting, it may be used by those who are unable to tolerate other treatments, including the elderly and frail. The company added that this potentially represents a significant benefit over existing treatment options as it enables a wider range of patients to be treated, including those who want to be treated closer to home. Being an oral capsule, it has the potential to present a lower overall burden on the healthcare system as compared to more complex therapies, such as cell-based therapies. In June 2023, CellCentric was granted orphan drug and fast track designation status from the FDA for inobrodib. Further clinical data will be announced at the American Society for Hematology annual meeting (ASH), San Diego 9-12 December 2023.