ASCO 2025 | Novel targeting of S100A9 with tasquinimod in multiple myeloma

So we’ve been working for several years now on a clinical trial of tasquinimod, which is an oral small molecule inhibitor of S100A9. And S100A9 is a protein produced by myeloid cells, and in multiple myeloma, that’s primarily myeloid cells in the bone marrow microenvironment that suppresses T-cell activity in the bone marrow microenvironment, promotes angiogenesis, and helps confer resistance in myeloma cells to currently available therapies like proteasome inhibitors and immunomodulatory drugs. And the work that we’re doing is based on laboratory work that was done by my colleague Yulia Nefedova at the Wistar Institute in Philadelphia, who showed in mouse models that if you treat mice with tasquinimod in combination with proteasome inhibitors or immunomodulatory drugs, you can achieve synergistic activity. 

So we started our trial a few years ago, first with single agent tasquinimod, and then in combination with the standard antimyeloma regimen of ixazomib, lenalidomide, and dexamethasone, or IRD. And what we’re presenting here at ASCO in 2025 is the basically final results of our trial where we’ve treated 10 patients with single agent tasquinimod and then 17 with the combination with IRD. And what our poster focuses on is the responses that we’ve seen in this combination in patients who were previously refractory to their most recent IMiD-proteasome inhibitor combination. So patients in whom we would not expect the IRD backbone combination to work on its own, and we did see one durable partial response that lasted over a year and a half in a patient who previously had been refractory to an IMiD-proteasome inhibitor combination, actually two of them. And additionally, we saw three minimal responses, so greater than 25% responses in patients who were also refractory to their most recent IMiD-PI combination. 

So we see enough evidence there to suggest that tasquinimod is having its hypothesized effect that we’re excited about the possibility that tasquinimod could be a real benefit to patients in various combinations. Now, we’re not sure that the IMiD-proteasome inhibitor combination is really going to be where tasquinimod will have its best value. I’ve been really excited about some recent data that’s come out in part from some of my colleagues at the University of Pennsylvania that suggests that myeloid cells in the bone marrow microenvironment and specifically S100A9 may play a role in treatment resistance for T-cell immunotherapies like bispecific T-cell engagers and CAR T-cells. And so we’re hoping that there may be a role for tasquinimod in combination with T-cell immunotherapy for myeloma in the future. 

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