Our hypometric agents use a lonely combination. In MDS today, they are approved alone. There are several combinations done that were not successful, such as histone that is inhibited or other compounds. Although today, there's new drugs being explored among the BCL2 inhibitors, PD1, PDL1 inhibitors, immune therapy added to hypometric agents in MDS. There are ongoing randomized trials. We are eagerly awaiting the results to see if we can further improve on HMA alone. Because HMA are effective, but they are not a breakthrough. We need really to build on them to make them better. That is an MDS. In AML, we succeeded to have a combination. In fact, in acute myeloid leukemia, especially in older patient population, we added a drug called Venetoclax or a BCL2 inhibitor. Again, the idea is these cancer cells, we need to put them to death because of this life cycle is being abnormal or perturbated. So this BCL2 inhibitor can put the cancer cells to die. Therefore, they are synergistic with the HMA. In that sense, there was a trial where we combined D-cytidine or A-cytidine with a BCL2 inhibitor, Venetoclax. We've seen the responses in AML going from 25% approximately to 65%. The survival went from 10 months to 16 months. That was confirmed in a randomized trial where patients were randomized to either HMA plus placebo or HMA plus BCL2 inhibitors. The new arm for BCL2 inhibitor Venetoclax plus HMA was A-cytidine, was found to be superior, higher response rate, better overall survival, and more education of the disease, and that has become our standard of care. So we moved from hypo-mating agents alone to a combination, and that was successful, and therefore now we have a new backbone to build on it. Building on it means maybe adding other target therapy, be it IDH inhibitor, flitry inhibitors, or others. So we're walking away from HMA to HMA combination to further improve the outcome.
