ASH 2023 | STIMULUS-MDS1: sabatolimab + HMAs in untreated HR-MDS

Yeah, so sabatolimab is a monoclonal antibody against TIM-3. TIM-3 is overexpressed in leukemia stem cells and blasts as well as in T-cells in patients with higher-risk MDS. Targeting TIM-3 with the antibody sabatolimab in preclinical data, as well as early clinical trials, has been shown to demonstrate clinical responses. And based on this, the antibody sabatolimab was taken into a randomized Phase II trial called STIMULUS-MDS1, where patients were randomized to receive a hypomethylating agent plus/minus sabatolimab. And we have reported the clinical outcomes of this, trial last year, actually in ASH 2022. And the data were just published three days ago, actually in the Lancet hematology paper.

What we have shown is that while the primary endpoint of the trial was not met, which was a combination of improvement in progression-free survival and complete response rate, but we show that the durability of the response among those who achieved responses was double that for those who are on the combination compared to monotherapy. But we also show that the progression-free survival appears longer and there is a late separation in the curves, suggesting impact of the immunotherapy. So this was already published.

What we show this year is additional analysis on the data set looking at the MRD clearance. And we know in AML that clearing MRD correlates with long-term outcomes. This data is just being generated in MDS. And indeed this is one of the, I think, first prospective clinical trial data sets that does demonstrate that patients who clear MRD seem to have better clinical outcomes, including survival. And we show that patients who receive sabatolimab with hypomethylating agent do have a higher rate of clearance of MRD. So I think it’s a proof of principle. It’s a relatively more limited sample size, but I think it certainly demonstrates the potential of this drug. Important to note that the Phase III trial of this drug, sabatolimab, has fully accrued more than 500 patients, and we are expecting results from this early 2024, which could be a major change in the landscape of treatment of higher-risk MDS patients.