HRO761 is a first-generation Werner helicase inhibitor. This year at ESMO, the first data on phase one of this drug has been presented and they show very encouraging results, either in terms of toxicity or in terms of preliminary efficacy. In tumors with deficient MMR or microsatellite instability high, we know that Werner helicase is synthetically lethal, and so it can represent a therapeutic target...
HRO761 is a first-generation Werner helicase inhibitor. This year at ESMO, the first data on phase one of this drug has been presented and they show very encouraging results, either in terms of toxicity or in terms of preliminary efficacy. In tumors with deficient MMR or microsatellite instability high, we know that Werner helicase is synthetically lethal, and so it can represent a therapeutic target. This small molecule inhibits the helicase domain of Werner, and in the phase 1 study that includes all patients with deficient MMR or MSI high, advanced solid tumors show a preliminary sign of activity with a favorable safety profile. The study included about 60% of patients with colorectal cancer and the others with other types of cancer that resemble the population of patients with MSI high, deficient MMR tumors that we see in clinical practice. Looking at the response, it was interesting to see that some patients derive a prolonged benefit, mainly stable disease with these new agents. But I think that for the future, there are two main points to consider for further development, either if we have to consider this drug as monotherapy in an advanced setting or more importantly to have some kind of combination therapy with immune checkpoint inhibitors and chemotherapy, and nowadays there are several ongoing trials that are trying to answer this question, but in conclusion, this is a very novel and promising strategy to treat this hard-to-treat cancer after progression to standard chemotherapy.
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