On April 2, 2021 Celleron Therapeutics, the UK-based company developing personalised medicines for cancer patients, reported that it has worked closely with Oxford University’s Medical Sciences Division to investigate the mechanism of action of zabinostat (previously known as CXD101) (Press release, Celleron, APR 2, 2021, View Source [SID1234577532]).
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The study found that zabinostat enhances immune-relevant gene expression. This effect leads to increased recognition of tumours by the immune system with enhanced anti-cancer activity. The study included a genome‐wide expression analysis and functional profiling, which uncovered enriched gene signatures and pointed towards a role for the immune system in how zabinostat acts. When zabinostat was combined with immune checkpoint inhibitors, such as anti‐PD1 and anti‐CTLA4, using tumour models that are normally unresponsive to mono-therapy, it resulted in enhanced anti‐tumour activity.
The recent scientific findings, published in the latest edition of Molecular Oncology, are highly consistent with the clinical strategy and clinical trial design which Celleron is pursuing in its CAROSELL Phase 2 clincal study, which investigates zabinostat and nivolumab combination treatment in patients with microsatellite-stable colorectal cancer (MSS CRC). MSS CRC, which remains clinically unmet, has been long establised as being unresponsive to immune checkpoint inhibitor monotherapy treatment. In addition to the novel combination therapy deployed in CAROSELL, Celleron plans to translate the key findings on gene signatures described in the study to predictive biomarkers that help identify patients who undergo a favourable response to the combination therapy.
Professor Nick La Thangue, CEO, commented: "This is a truely fascinating study. It represents a major milestone in understanding zabinostat but most importantly opens up new ways of identifying cancer patients that are likely to undergo a good response to the drug. We will deploy the new information to strengthen our precision medicine platform to maximise the therapeutic value of zabinostat for cancer patients".
Professor David Kerr, CMO, commented: "This excellent science provides a platform which we can use to identify patients who are most likely to respond to zabinostat, significantly increasing the likelihood that our clinical trials will yield a positive result and benefit the community of cancer patients whom we serve. Equally as important, it opens up new avenues of clinical research in which we can deploy zabinostat in combination with a wide array of immune therapy approaches to improve their effectiveness".