EHA 2025 | Phase I results of bexobrutideg (NX-5948) in Waldenström’s macroglobulinemia

So, bexobrutideg or NX-5948 is a BTK degrader. So, we’ve all been using BTK inhibitors in our everyday clinical practice. So, the covalent BTK inhibitors first came along, then the non-covalent BTK inhibitors. But we think BTK also, as well as having enzymatic activity, probably plays a scaffolding function within the cells. And so by degrading the protein, you’re not only removing the enzymatic activity, but you’re removing the scaffolding function as well. And so we know that BTK degraders potentially could work even in patients whose diseases become resistant to BTK inhibitors. 

So there’s currently a Phase I trial that we’re participating in looking at the use of NX-5948 across a range of B-cell malignancies and at EHA this year we’re presenting the data from the patients who have Waldenström’s. So it’s just over 20 patients who’ve had the NX-5948 and the response rate is really encouraging. So over 80% of patients responding. The response is quick, so average time to response is less than a month when we start to see already patients’ disease improving. And obviously it’s an early phase trial and it’s still relatively short follow-up, but there have been a few patients that have had the treatment for over a year and are still getting durable responses. So still very early days, Looking forward to seeing the expansion cohorts to see its effect in more patients and to see the development of the drug across B-cell malignancies, but really encouraging data from this trial so far in WM.

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