 Cellinaxor is actually the first in class selective inhibitor of this protein. This protein is called exporting one and this protein is like the function is think about the chaperone carries out from the nucleus different type of tumor suppressor proteins, oncoproteins, glucocorticoid receptor and so the cells don't go to the regular cell that they don't die. And so cellinaxor and this protein is highly expressed in myeloma cells associated with the poor prognosis. So cellinaxor inhibits this protein so this pretty much this protein this tumor suppressor protein etc. don't leave the nucleus and so the cells will eventually go to apoptosis which is the diet the regular you know do the cycle of cell death. So I've been working with cellinaxor now for a few years as part of the stomp trial. The stomp trial was designed to combine cellinaxor with Lodos dexamethasone with different backbones treatment. For instance we have tested the cellinaxor in combination with lanalidomide, pomalidomide, bortosemab, carfilzomeb, daratumab, so a little bit old the major back bone treatment and the patients were assigned to the different arms based on their prior therapy. For instance if there were carfilzomeb naive they were assigned to the carfilzomeb cellinaxor dexamethasone arm. So it's an interesting design but allows us to test the the drug in different combinations you know in different time point stage of their disease. So the results are actually very encouraging with all the combinations. Last year I presented the combination with daratumab, cellinaxor dexamethasone, we are in the process of publishing that and it was you know first of all every single arm has a phase one where we determine what the tolerated those for the particular combination and then each arm were suspended with the recommended phase two portion those and so the daratumab was incredibly effective leading to around 70 percent response rate and it was durable some of the responses were durable in fact I have a patient that is going for three years on this combination. This year Adash I had a poster yesterday on the combination of carfilzomeb cellinaxor dexamethasone and we just completed the phase one B portion of the study so we are expanding we're going to phase two we found that the dose of cellinaxor was 80 milligrams weekly with a carfilzomeb 56 milligram per meter square weekly we treated only 14 patients at this dose we didn't have any dose limiting toxicity and the overall response was 71 percent we also had an incredible amount of VGPR 50 percent VGPR and 20 percent complete admission and interestingly you know all these patients were carfilzomeb naive or whether the medium prior lines of therapy was about four and 50 percent was actually daratumab refractory and we had a very similar response rate about 70 percent for this population of patients so we were very encouraged by the preliminary results is very well tolerated overall and we have few patients going for one year continuation of therapy so we hope to have more robust data relatively soon they're similar or whether they are much less because in all these combinations the cellinaxor is given weekly and when you use the cellinaxor in a weekly rather than bi-weekly there are some GI but they were all grade one and two actually very manageable so less of the nausea the vomiting the way loss so we didn't have we only had a couple of patients with hyponitremia which was you know one of the side effects in this storm trial we had myelosopression I think a thrombocytopenia remains one of the major toxicity of the different combinations we support patient aggressively we give actually in plate weekly maintain the platelets level in fact two of the dose limited toxicity at the higher those were thrombocytopenia and we continue to observe some thrombocytopenia throughout I didn't mention that yesterday there was also the presentation the oral presentation with Christine Chan was part of the arm with the cellinaxor pomalidomide axomethazone also leading to a 56 overall response rate in patients you know kind of sensitive to pomalidomide or whether 30% were exposed to pomalidomide so again we see another oral very promising combinations so I think in my experience working with the cellinaxor now for a few years I noticed that the first couple of cycles are probably the most critical adjustment and we're trying to push the dose you know during the first couple of cycles the response is very rapid and then with aggressive supportive care and dose adjustment as I say I have a patient going for three years so you know as long as you aggressively support patient with antibiotics fluids proper dose adjustment is actually relatively well tolerated overall is by mouth once a week so I really in particularly with the carfilzomeb or the daratumumab but I didn't have any major toxicities beside the aspected one the cellinaxor was approved in combination with that Daxa here in the United States has a bi-weekly administration with the overall response of 26% in very heavily treated patients now in the combinations we're going a little bit earlier once a week and you know we don't have many of the side effects that we're seeing with the bi-weekly administration I think that's an important point because when the drug the combination was approved everybody was concerned about management of toxicities but I have actually a more positive experience so I think the carfilzomeb Daxa-Metazone cellinaxor combination could be an important triple combination for patients exposed in refractory to daratumumab as I mentioned about 67% were exposed to daratumumab 50 were refractory and you know daratumumab is going early in a from satin already approved transplant ineligible you know with the Maya etc and and so we see more and more patients exposed to daratumab and and we have data showing that these patients after failing daratumab they really don't perform well they had the difficult time and so I think this combination could be a promising combination as a sequential next step for some of these patients