Hello. My name is Keith and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics ASH 2020 Investor Conference Call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request.
I would now like to turn the call over to Mr. Ian Karp, Caryopharm Senior Vice President, Investor Relations.
Great. Thanks so much. And thank you all for joining us on today's conference call. To discuss important clinical data presented at the American Society of Hematology 2020 annual meeting. This is Ian Karp, and I'm joined today by Doctor.
Michael Kaufman, Chief Executive Officer Doctor. Jaden Shah, Chief Medical Officer, as well as my 2 guests on today's call who will join us a bit later, Doctor. James Barrington, Founder, President, and medical and scientific director of the Institute for myeloma and bone cancer research, and Doctor. Timothy Pardy, Director of Lukemia Program at the Wake Forest School Medicine. On the call today, Doctor.
Coppell will provide a brief summary of the role XB-one plays in the development and proliferation of many types of cancer, and will also provide a short overview of the current treatment landscape in multiple myeloma. Doctor. Shaw will then provide a summary of the key presentations at ASH this year, that highlighted data from our Boston and Stomp studies in multiple myeloma. He will then provide a brief overview of the treatment landscape in DLBCL, along with the data from the SADO study, which was also presented in NASH. We are very fortunate, as I mentioned, to have 2 well recognized experts in the fields of multiple myeloma, and leukemia joining us on today's call.
Doctor. Barrington and Pardee will offer some of their own insights on the data presented at ASH as well as will join us for the Q And A portion of the call. Additionally, Doctor. Pardy will review data from an investigator sponsored study he is leading at Wake Forest Baptist Health in the frontline setting for patients with acute myeloid leukemia or AML, which were also presented yesterday at the ASH meeting. Please note that doctors, Barrington and Parete, are not employees of Keriopharm and have been invited to participate on today's call as they are experts in the field of hematological malignancies.
Their comments and opinions shared today are completely their own, and do not reflect official statements from Karyopharm or their institutions. Yesterday, we issued 2 press releases detailing exposure data presented at this year's annual ASH meeting. These releases, as well as a PDF copy of this presentation, will be available on the Investors section of our website at carriedfund.com. Before we begin our formal comments, I'll remind various remarks we will make today constitute forward looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, including our expectations related to the commercial relations exposure, financial projections and our plans and prospects.
Actual results may differ materially from those indicated by these forward looking statements, as a result of various important factors, including those discussed in the Risk Factors section of our most recent quarterly report on Form 10 Q, which is on file with the SEC. And in filings we may make with the SEC in the future. Any forward looking statements represent our views as of today only, but we may elect to update these forward looking statements at some point in the future, We specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Doctor.
Michael Kauffman, Chief Executive Officer of Karyopharm.
Please continue to hold the line. Doctor. Kaufman has just disconnected. I will reconnect him.
There's technical difficulties we can proceed. Let me know. This is Doctor. Shaw. Okay.
One moment, please.
You know what, for the sake of time, why don't I start with the Pieris 3 slides, and then I'll, we'll transition over to Doctor. Shah, shortly as, as Doctor. Kaufman is dialing back in. So, so first, let me begin. Really with a bit of background as we're delighted to discuss some of the key exposure of clinical data presented at the ASH 2020 meeting today.
We are particularly fortunate this year to be able to present a large and diverse set of data, which span across disease states, including multiple myeloma, lymphoma and leukemia. This was in part due to the growing recognition within the oncology research community that Expevio is playing a fundamental role in the proliferation of many cancers. And this is where we'd like to begin. And before we actually move to the clinical data, which Doctor. Shaw will present for us.
Now as many of you may know, there are 5 foundational pillars of cancer drug therapy, which are used across tumors and patients, often in combination to provide each patient the best chance at beating their disease. Exmovio, which particularly, which specifically targets a protein called Xb01, is the 1st anti cancer drug whose primary activity is the activation of tumor suppressor proteins. There are about 20 of these proteins, including P53, BRACA 1, and 2, RB and the inhibitor of NF Kappa B, called Icap B, which are critical parts of each cell's own natural defense mechanism to detect cancerous DNA changes and prevent the generation of the immune cell. In short, Expobia could direct the cell, which has become cancerous, to commit suicide and potentially improve outcomes for a large variety of cancer. With that, I want to just check Steve, Michael, Doctor.
Kaufman has made it back on the line. And if so, we can move to Slide 6.
Yes. Thank you. I apologize. I was kicked out. Somebody obviously did not like me.
So Let me find Slide 6, and we will move ahead. And I appreciate everybody's patience here while we dig into there. My apologies, Ian. I I don't know where to pick up. I apologize.
Sure, Michael. We're just on the slide now that has the, the 4, the photographs of XPO levels correlated with 4 cancer prognosis for patients.
Yes. So, as you can see from 4 separate graphs, which highlight previously published clinical data, higher ex P01 levels are correlated independently with overall survival in patients with myeloma, diffuse large B cell lymphoma, soft tissue sarcoma, glioblastoma, and many others where we, where we didn't have a room to, present. The main point here is that over the past 5 years, it has become increasingly evident that the overexpression of XP01 plays a critical role in oncogenesis, largely by removing tumor suppressor proteins from the cell nucleus where they normally function. XPOvo forces the retention of these proteins in the nucleus and keeps them there restoring their tumor suppressor function. And that's why we've developed such a broad clinical program for Xpovio across many different tumor types.
Xpovio is an oral selective Xp0one inhibitor, that first reactivates multiple tumor suppressor proteins relevant to many cancer types second, inhibits nuclear factor, CAPA B signaling 3rd, reduces CMIC and other Onco protein levels and 4th, reactivates glucocorticoid receptor signaling in the presence of steroids. Such as dexamethasone. Based on these important mechanisms, Xpovio demonstrates synergistic activity in combination with bortezomib, pomalidomide and lenalidomide and other anticancer drugs in vitro and in vivo. And due to the broad applicability of Xpovio across different tumor types, You can see that on the next two slides, just how diverse our clinical development approach is. Here you see our current and planned clinical trials in multiple myeloma, DLBCL and myelofibrosis.
I'll also highlight a new Phase III trial in multiple myeloma that we plan to start in 2021, which will evaluate the combination of Expovia with pamilis and dexamethasone compared to pamilis and dexamethasone alone, which if successful, could offer a very compelling all oral regimen for multiple myeloma patients in the future. Next, while we won't spend much time today talking about our plans and operations in solid tumors. It's important to see the broader plans for Expovio where we're currently studying it across a number of solid tumor indications. Including the phase 3 C ENDO study as frontline maintenance therapy in endometrial cancer. Further, we're exploring a number of new trials, which could start in 2021 including myeloma treatment landscape before I hand things over to Jatin to discuss our myeloma data presented at ASH.
There are currently 4 main classes of drugs commonly used to 3 patients with myeloma, which include proteasome inhibitors, immunomodulatory agents, monoclonal antibodies, and now a nuclear export inhibitor, where of course Xpovio is the only drug in this class. Patients typically receive 1 or 2 of these highly active agents in combination with a steroid such as dexamethasone in each line of therapy, and they're usually treated until their disease progresses. Physicians will then typically prescribe another combination, including steroids, in each of the subsequent lines of therapy. Our experience is that physicians generally prefer to combine at least 2 drugs with distinct mechanisms and proven single agent clinical activity typically with the additional steroids. And furthermore, there are a number of key features that can help predict the usefulness and ultimately the success of a new multiple myeloma drug, which include demonstrating the following significant single agent activity, efficacy and heavily pretreated disease, compatibility to pair with drugs from other classes, tolerable and manageable side effects with minimal overlap in toxicity with other myeloma drugs that could be used in combination.
Robust Phase III data to support earlier line use, the ability to continue the agent indefinitely until relapse. And finally, the potential to use in a frontline regimen. We believe that Xpobio satisfies all of these features that may help predict the ultimate usefulness of a new myeloma drug. And much of the data presented at this year's ASH will help support a number of these dynamics. And the fact that Expobio is typically given orally only once per week make it particularly interesting partner with other agents.
Finally, we eagerly await a decision from the FDA regarding our SNDA for previously treated myeloma patients based on the Boston study. As a reminder, in Boston, we evaluated weekly Xpovio in combination with weekly Velcade and low dose dexamethasone. The Boston regimen Loys a completely novel synergy by combining an XPL1 inhibitor with a proteasome inhibitor. And based on the BOSTON results, We believe that treating patients with such a combination as early as possible may be vital for successful patient outcomes. If approved, I want to highlight the potential for Expevio as part of the Boston regimen to be.
1st, the first new mechanism approved since 2016 for patients following their first relapse. The only approved once weekly Velcade combination regimen. And third, a regimen with demonstrated rapid and sustained response despite the large percentage of patients with high risk cytogenetics in the pivotal Phase III BOSTON study. With that, I'll now like to hand over the presentation over to Jatin who will walk us through some of the key exposure data presented this year at ASH.
Perfect. Thank you, Michael. So I'd like to first begin with the data from the Phase 3 BOSTON study now published in the Lancet. Which enrolled 402 patients and this is a combination of once weekly oral selinexor once weekly, which is otherwise known as Velcade, and low dose dex Methzone compared to standard twice weekly vortism and moderate dose dexamethasone in patients that had received 1 to 3 prior therapies. Throughout the remainder of today's presentation, we will refer to these 2 treatment regimens as SBD and BD, respectively.
Now as you may recall, the top line results of the BOSTON trial showed a significant reduction of 30% in the risk of progression or death in patients receiving SVD as compared with standard BD with P value of 0.0075. Our number of post hoc subgroup analyses were conducted on the Boston data and presented at ASH, which we'll review today. Now, the first BOSTON subgroup analysis that I'll highlight evaluated the effect of prior treatment with protease on hibbers on the efficacy and safety of EXPLOVIGO. The median progression free survival was improved with SVD treatment compared with BD treatment for patients with prior proteasome inhibitor therapy. As well as those who are PI naive.
For patients who are PI naive, there was a significant benefit in progression free survival with SPZ treatment. As the PFS was not reached, yet in that group, with a hazard ratio of 0.26. These results support the idea of using Xplovia with Bortizumab as a patient's first PI combination therapy. For patients that had prior PI therapy, the combination of the SVD also led to a significant improvement in the overall response rate, from 59.7% in the VDR, 77% in the SVDR improvement in the depth of response. There was an increase in the complete and stringent complete response rate from 9.4% in the VDR to 14.8% in the SVD arm.
Now furthermore, the use of autism based regimens is common in newly diagnosed multiple myeloma. Especially in patients who go on to receive a stem cell transplant. Therefore, we specifically looked at patients that received a participant based therapy prior to stem cell transplant and a long reticement treatment free interval prior to entering the study. This is a common treatment paradigm here in the U. S.
In these patients who received a prior PI therapy before receiving a stem cell transplant, SVD treatment led to an improvement in progression free survival from 9.4 to 13.1 months in SVD from a hazard ratio of 0.58. Non peripheral neuropathy is either higher within the SCV arms than the BD arms of most of the AEs were reversible and treatable. Thrombocytopenia was more frequent in patients in the SVB arm as was anemia, fatigue and decreased appetite, among others. In contrast, peripheral neuropathy, which is the most common and important cause of continuation at Fortismit and can cause chronic even lifelong pain was observed less frequently on the exposure arm than the control arm. Thus, on a pre specified endpoint of peripheral neuropathy of grade 2 or higher, less peripheral neuropathy in the SVDR compared to the VDR.
To our knowledge, this is the first study where a triplet autism continuing regimen at lower rates of neuropathy than the Mortissimic compared to our regimen. Overall, once weekly SVD is an active and convenient regimen, and if approved, may become an important treatment option for patients on the relapsed or refractory myeloma, who had prior PI treatment such as borticillin based induction therapy, or those who are PI naive. The next subgroup analysis from the BOSTON study looks at the impact of prior therapies and not just prior protease on inhibitor therapy on the safety and efficacy of EXPLOREO. Of particular importance in this analysis, when the data for patients who had received prior lenalidomide or imid based therapy. Similar to the lenalidomide naive patients, patients treated previously with lenalidomide showed a significant improvement in the response rate with SVD treatment compared to BD treatment.
The durability of the response and progression free survival was significantly longer following SVD treatment compared to BD regardless of prior lenalidomide treatment. The hazard ratio for the progression free survival was 0 point 63 in patients with prior lenalidomide, which is very similar to the hazard ratio of 0.66 in patients who are lenalidomide naive. The longer PFS seen in lenalidomide naive patients appears to be driven by the fact that these patients were in 1st 3 months. For patients with 1 prior treatment, as well as patients with 2 or more prior treatments, the overall response rate is significantly higher in patients with SVD compared to the BDR. In addition, the durability of response was also higher in the SPD treated patients as evidenced by the significantly longer progression free survival and hazard ratio of 0.63 and 0.69.
Notably, the VGP are more frequent from both patient populations when treated with the SVD as compared to BD. Grade 2 or peripheral higher neuropathy occurred significantly less frequently across all Sbd stem groups compared to the BD groups. Consistent with previous subgroups, adverse events of great deer higher notably thrombocytopenia anemia and fatigue were more commonly reported in the VD treatment arm and the VDR, and were mostly managed with dose modifications and our supportive treatment. There were no differences between some groups in Grade 3 and events. In summary, regardless of prior lenalidomide treatment, The combination of SVD was active when the PFS has a ratio of 0.63 among patients with prior monolumide treatment received SVD compared to BD.
Now this is particularly compelling with ability to incorporate 2 new class of therapies in patients progressing on 111 and therefore, leveraging the common practice of class switching in myeloma. In addition, regardless of prior treatment, SVD treatment led significantly improved overall response rates and progression free survival, with the highest PFS of 16.6 months seen in patients following first relapsed Now, the next subgroup analysis from the Boston study presented that ASH evaluated patients with high risk disease versus standard risk disease based on recognized other genetic factors. SVD treatment improved progression free survival compared to VD treatment across all subgroups that sub translocation 1416, which will have the smallest subgroup. Notably in patients with both 1 cytogenic abnormality or patients with 2 or more cytogenic abnormality, the PFS was improved in the SPD of arm comparative to the BDR. The time to next treatment was also significantly increased with SVD in a high risk and standard risk patients, overall response rate was also significantly improved with SVD in the high risk group and numerically improved in the standard risk group when we've comparable rates between the high risk and standard risk groups in the SVD arm.
The safety profiles of SVD and VD and the high risk and standard risk groups were consistent with the overall population. Again, consistent with what we described peripheral neuropathy, adverse events on grade 2 or higher were lower with SVD compared to BD in both the high risk and standard risk subgroups. In summary, SVD treatment was superior to BD treatment, including in patients with high risk disease, as supported by the progression free survival in the different subgroup of patients high risk therapeutics. Patients with high risk surgeons, including deletion 17p, need new options for the novel mechanism of action. Expobio's novel mechanism, reactivating tumor suppressor proteins, and reducing levels of ongoing proteins may be particularly suited for patients with high risk multiple myeloma.
In non peripheral neuropathy adverse events who are higher with SVB and mostly the adverse events were reversible. The final subgroup analysis in the Boston study presented at ASH evaluated patients by both age and frailty. Now similar to younger patients, the overall sponsor is significantly higher with SV treatment in patients when we're or 65 in order. And FPD is also associated with a longer progression free survival with a hazard ratio of 0.55 in older patients. Overall, for both age categories, the BGPRA rate was also higher with SVD treated patients compared to those treated with BD.
Now regardless of whether the patients were fit or frail, the combination of SPD led to a higher response rate and a VGPRA for patients treated as PD. Importantly, the pro haptic ratio was 0.69 was the same for both fit and failed patients. And a progression of pre survival with FPD treated patients was 13.2 and 13.9 patients both hip and pale patients. Similar to the overall population, the most common grade 3 or higher adverse events for thrombocytopenia, anemia pneumonia and fatigue. In the SVDR, the incidence of AOS compatible across all the subgroups, except for a lower incidence of diarrhea and vomiting, the higher incidence of nausea, fatigue, and insomnia in patients 65 or older compared to those younger than 65.
Among the frail patients, the AEs were comparable to 5th patients SED, except for an increased incidence of Asthynia and pneumonia in the frail group. Overall, thrombocytopenia was more common in the SCD ARP than the VD Arm. In summary, both elderly and failed patients benefited from SVD treatment compared to the D and D treatment. Activity of SPD was preserved in patient 65 or older with a PFS of 21 months compared to 9.4 months for patients treated with BD. And a hazard ratio of 0.55.
SVD also had a similar progression free survival in both fit and frail patients. Now with my review of the data from the BOSC Place now complete, I will I will review the key data from the 3 presentations, holiday data from our stop study. As a reminder, Stump was a multi center open labeled dose escalation Phase 1 and dose expansion phase 2 study. To assess the maximum tolerated dose, efficacy and safety of selinexor, in combination with other backbone myeloma treatments in patients in relapsed myeloma. The first armament study I'll discuss is the combination arm with pomalidomide, otherwise known as palm and low dose dexamethasone or SPV, which is highlighted in oral presentation today.
After the 65 patients enrolled, 60 were deemed evaluable for efficacy. Among the 46 patients who are POM naive or not refractory to pomalidomide, the response rate was 54%. And among the patients who are pomalidomiderefractory, whose disease is pomalidomiderefractory, the overall response rate was 36%. Note that reviews and recommended Phase 2 dose of selinexor60 milligrams once weekly and POM4 milligrams and response rate were 60%. The waterfall plots are seen below highlight the depth of response.
The SPD regimen was highly active with durable responses and a prolonged PFS and duration of response. The median PFS was 12.3 months among patients who are palm naive or who do not have palm refractory disease. The median DOR was 11.3 months. The progression free survival and DOR have not been reached yet for the 20 patients a dose at the recommended phase 2 dose. Common hematologic treatment related adverse events included neutropenia, immediate and thrombocytopenia.
In common non hematologic side effects, included nausea, fatigue, decreased appetite weight loss in diarrhea. Most of the non hematologic side effects were low grade, and all of these side effects were expected and managed with supportive care and dose modifications. In summary, we believe Expilio given once weekly can be safely combined with pomalidomide and low dose dexamethadone in patients with heavily pretreated myeloma. The recommended Phase 2 dose of selinexor 60 milligrams palmolutamide 4 milligrams and dexamethasone 40 milligrams, all given once weekly, with the homalidomide given days 1 through 21. All oral SPD combination was very active and produced responses, which were durable with our sponsor to 60% at the recommended phase 2 dose, and this is in comparison to an expected overall response rate of less than 30% for Palmdex alone.
These data support a planned Phase 3 study of the all oral combination of FPD versus PD in patients with prior PI imminent CD38 monoclonal antibody. Here you can see the design for our planned Phase 3 study of selinexor pomalidomide indaximethzone, which we expect to start in 2021. And we believe if positive, could significantly add to the current myeloma treatment paradigm by offering patients a highly active and tolerable all oral active regimen. The next arm from this Tom study highlighted ASH came from the arm of validated Espovio in combination with cargosin with Andexametho. Or SKD.
SKD treatment resulted in deep responses in heavily pretreated patients, including 2024 efficacy evaluable patients. Among these 24 efficacy evaluable patients, 5 patients achieved a complete response, These patients achieved a very good partial response and 5 achieved a partial response. The overall response rate was 75%. And the clinical benefit rate was 79.2 percent. The responses to the SKD regimen were also durable median progression of pre survival was 23.7 months for all patients and 12.7 months among the 17 patient dose at the recommended phase 2 dose.
The swimmer's plot shows 5 out of the 18 responders were still on treatment as of the data cutoff with the longest patient staying in the treatment for 25 months. Common triplet hematologic adverse events include a thrombocypnea and anemia. Common non hematologic adverse events included nausea, fatigue, decreased appetite and weight loss. You have asked majority of the day these on grade 1 or 2. Mode deaths were low deaths due to adverse events reported, and all of the adverse events including Grade 3 and Grade 4 thrombocytopenia were successfully managed with supportive care and dose modifications.
In summary, the recommended Phase 2 dose of SKD with continuous weekly selinexor is once weekly selinexor 80 milligrams Once weekly carfilms, 56 milligrams per meter squared and dexamethlon 40 milligrams. This combination is active and durable with a response rate of 75% a deep responses and a greater than a VGPO rate of 54% in patients with a median three lines of prior therapy. Finally, the last arm of the STOMP study presented at ASH came from the lenalidomide arm of the study, which evaluated Xplovio in combination with lenalidomide and low dose dexamethone in patients with both newly diagnosed and or relapsed to refractory myeloma. For the 12 evaluable patients with relapsed or refractory disease where lenalidomide naive, one patient achieved a complete response 4 achieved a very good partial response and 6 additional patients achieved a partial response for an overall response rate of 91.7 percent among the 12 lenalidomide naive patients. All seven efficacy evaluable patients with newly diagnosed myeloma achieved their response with an overall response rate of 100% including depromissions with one patient with a CR 4 patients with a VGPR and 2 patients with a PR.
The waterfall plot shows reduction with M protein baseline levels by more than 50% in 15 patients with relapsedrefractory disease, and all patients were newly diagnosed with multiple myeloma. Importantly, the RRD regimen results in durable responses, I think the swimmer's plaziers shows among the 12 responders who believe the PR with relapsed myeloma and 4 were still on treatment as of the data cutoff, a PFS greater than 35 months with the longest patient staying on treatment for greater than 50 months, correction for approximately 50 months. The median PFS was assessed as 9.6 months, with 2 patients with newly diagnosed multiple models are still on treatment as of the data cuff or having time on therapy greater than 24 months. Common treatment related adverse events in patients with relapsed myeloma were thrombocytopenia, neutropenia, nausea, fatigue, and decreased appetite. In combination in summary, the combination is highly active when the overall response rate of 100% in newly diagnosed multiple myeloma and 92% and lend over my 90 patients when relapsed myeloma.
These responses are durable with some patients staying on treatment greater than 2 to 3 years. Therefore, the all oral combination of selinexor lenalidomide and dexmedsone appear to be highly active well tolerated in the warrants further investigation. Having now reviewed the Boston subpopulation data announced presented at ASH as well as a 3 stop presentations. I'd like to ask Doctor. Barrenson to take a few minutes to provide his thoughts and implications from this combination data.
Yes. Good morning or afternoon. So, I think the results of this are, I've been, very impressive, particularly the kind of response rates that we're seeing with selinex or with Lundex, are incredibly impressive, and the durability that we've seen, with this. I really like the fact that we've learned how to use this drug that the lower doses, which we're now using in clinic, as well as the clinical trial, we're actually doing a trial with this triplet right now. We just got results, very nice results with Sully Lin on a we're doing a Lend resistant trial just to make sure that Sully can overcome Lend resistance.
And We're enrolling several others in the next 2 weeks. So we've been very encouraged by this. And we've been doing this off trial in the clinic for the last year. Off label, of course, with good results as well. And I think the doses that we're using now, we're finding are highly effective without all the toxicity that we saw early with the 80twice weekly dosing.
And we've been able to get in front of the GI and the nausea, the vomiting toxicity, the anorexia with the, the anti medics and then the olanzapine when we need it. In addition, I've been a big proponent in the Boston trial of giving less doses per month and less bortismant per month, and we're seeing that reflected here with a reduction in the neuropathy that in terms of tolerability, in this trial, of course, the dose that was used was higher with the celliot 100 once a week. But again, we've seen a very good ability in this randomized phase 3, Acelity to boost the activity of the proteasome inhibitor, bortzism and dexamethasone, with, at the same time, a reduction nicely in the peripheral neuropathy. And this is certainly the biggest conundrum of using bortizumab And I've been a firm proponent for now 20 years. I'm using only 4 doses a month and actually using a little less drug they use 1.3, which is the label dose in the study.
But again, the durability here has been very good. And again, in the randomized phase 3, we saw the ability of this to be superior for Bort, Tizumet, index alone. We are trying this drug in many other different applications off label. We certainly used it with multiple proteasome inhibitors. And we've used this now with multiple immunomodulatory agents.
And I think that we're learning more how to use this. We, we are certainly interested in perhaps alternative lower dose schedules that may be more frequent dose, we don't have any data on that clinically. We're just doing preclinical work with the sport now of Cariopharm. But look at that possibility But I think that, as you get to learn more about this drug, you're more impressed with it. Its ability to overcome resistance to plethora of other drugs.
And we certainly, again, have seen that in the clinic now, people who have seen revelment and been refractory. And I mean, really refractory, progressing right through it, you add selling and you can overcome the refractoryness without And then I would, I would chime in that the toxicity in terms of GI is one that we're seeing early and we tend to get reduced over the 1st couple of cycles, it seems to be much better tolerated. But again, the lower dose in general has been well tolerated too. Even when combined with other agents that may have toxicities. So, again, I think this is a drug that is a work in progress that will have much use in combinations.
Lots of other drugs have also been impressed of course off label with the DAR data That certainly seems to boost our activity quite a bit. We know that DARADEX alone has only a minority of patients responding yet in this early data, it looks promising it's a much higher proportion than that here. So I think this will be another arrow in our quiver to knock out myeloma over the next few years.
Awesome. Thank you, Doctor. Barrington. Appreciate that insights and the perspective. I'd now like to switch gears a bit and talk about DLBCL and the subpopulation data from our SADAL study, which was presented at ASH and begins on Slide 56.
On the treatment landscape in 2020 for DLBCL patients, and has evolved significantly over recent years with the approval of new agents, including EXPARELBIO as well as CAR T therapies. However, unfortunately, for the approximately 40% to 50% of patients not cured by the initial treatment with chemotherapy and rituximab, you have progressive disease. If they're fit or healthy enough, they often will go on to get another course of combination chemotherapy followed by stem cell transplant. Some patients may also go on to receive CAR T cell therapies at their appropriate candidate following progression after second line treatment. However, for those patients who are not fit enough for a transplant or CAR T cell or for those whose disease progresses after their second line treatment, These patients will then require a third line treatment option and for many additional treatment options in the 4th line or later.
This is the patient population with the greatest level of unmet need, and currently, for which Xplopia recently have received FDA approval in June 2020. This approval is based on a phasehold study, which included 134 patients, who have been previously treated at least 2 prior multi agent chemotherapies, We included both patients with GCD and non GCD subtypes in DLBCL. Importantly, patients with either de novo or legal lymphoma were enrolled in this study, and patients receive a starting dose of 60 milligrams of selinexor twice weekly. The study demonstrated an overall response rate of 29%, including 13% of patients achieving a complete response, and 16% achieving a partial response. Importantly, the median duration response was 9.3 months, with nearly 40% of responders remaining on therapy and in responses for at least 6 months.
The final data for the SADAL study was published in June of this year in the Lancet Hematology and 2 important subpopulation analyses for the study were just presented at 2020. The first analysis look at the effective age on the efficacy and safety exposure. In this sub analysis, there was no statistical difference in the response rate in patients less than sixty five years old versus greater than 65. And the complete response there is 17.3% and 11% respectively. Importantly, the responses durable and the median duration response was similar at 9.7 months in patients less than 65 9.2 months in patients above 65.
Caution in patients at least 65 at all. The incidence of treatment related adverse events were comparable between both groups. Older patients have less thrombocytopenia and anemia, however, as expected, had more nausea, vomiting, fatigue, and asthymia. Overall, the common grade 3 or higher adverse events or thrombocypemia, nausea and fatigue which can be again managed with dose reduction in supportive care. In summary, patients with a relapsed large cell lymphoma who are sixty five years or older, a similar clinical benefit to those younger patients when treated with selinexor with comparable response rates CR, aggression, survival, duration response, and safety profile.
The second subpopulation analysis from the state of study presented at ASH was at the impact of renal function on the efficacy and safety profile of EXPARELVIO. Treatment with Xplovia demonstrated a similar overall response rate in patients with a baseline reduced creatinine clearance versus those patients with a normal creatinine clearance. The complete response was observed in 21.6 percent of patients in the reduced creatinine clearance and 10.3 percent of patients with a normal creatinine clearance. The median overall survival in patients with a reduced creatinine clearance was 7.8 months compared to 9.1 months in patients with normal creatinine clearance. The incidence of treatment related adverse events was comparable between both groups.
Most common, great, clear, higher treatment related adverse events for patients with reduced versus normal creatinine clearance, thrombocytopenia, nausea and fatigue, which can be managed again with supportive care and dose modifications. These side effects were similar regardless of renal function, with an increase in the medium, vomiting, and diarrhea in patients with renal dysfunction. There was no clinically significant increase in treatment related serious adverse events or adverse events leading to discontinuation in patients with a reduced or normal creatinine clearance. In summary, Xprogio showed similar response rates in tolerability in patients in relapsedrefractory large cell lymphoma regardless of the renal function. This is important because Xplovio is not metabolized or cleared by the kidneys.
And is approved for pay approved for use in the patients with severe renal dysfunction. No dose adjustments are required in patients with renal dysfunction, for patients with renal dysfunction and DLBCL who are treated with EXPAREL. Now with my review of the SADAL data presented at ASH Complete, I'd like now to ask Doctor. Part D to review the data from the investigator sponsored study immediate wake for us, which is evaluating frontline selinexor in combination with chemotherapy in patients with, AML. Doctor Pali.
Hey. Good afternoon. Can everybody hear me okay?
Yes.
Great. So, I'd like to just briefly take you through the data that I was able to present at ASH yesterday. We conducted a frontline trial of selinexor in addition to induction chemotherapy for patients with acute myeloid leukemia who are sixty years of age or older. It turns out that age is quite prognostic in AML. And adults sixty years of age or older do quite poorly.
They are very poorly responsive to chemotherapy. And some meta analyses have shown 5 year overall survivals for these patients of less than 10% with the study on the slide that's being displayed showing you a 6.6% of 5 year overall survival. So there's clearly a need for novel approaches On the next slide, you'll see the schema for our study, which was a 1 to 3 randomization, between the standard of care cytarabine and Donnarubicin, the 7+3 regimen, versus the same 7+3 regimen with the addition of a flat dose selinexor at 60 milligram twice weekly for 3 weeks. As, per the standard treatment for these patients, there is a day 14 bone marrow biopsy that's done to assess initial response. To the chemotherapy.
And if patients require a second induction cycle, it's an abbreviated cycle. We call that 5+2. The control arm got, the standard 5 to the treatment arm, the experimental arm got 5+2 with the addition again of selinexor at 60 milligrams twice a week for 3 weeks. On the next slide, responding patients could go on to get consolidation chemotherapy. Again, this is a standard practice.
And so patients could get up to 4 cycles of, hydrocyteravine consolidation in the standard of care on by itself and in the experimental arm in combination again with selinexor at a flat 60 milligram dose twice weekly for 3 weeks. And then finally for patients on the experimental arm, who had completed all planned consolidation therapy and were not moving on to an allogeneic stem cell transplant. There was an option for those on days 1 in 8 out of every 21 days. And they would continue on that until, relaps or unacceptable toxicity. The next slide shows you the demographics of the patients that we enrolled, on our study.
We had 7 patients enrolled in the standard of care arm and 21 patients in in the selinexor arm. There were, slight differences in age. So the median age of the standard care arm was slightly older at 74 compared to the selinexor arm at 67. There was also an imbalance in gender. And so there were no male patients enrolled in the standard of care arm.
So all seven patients were female. This was a statistical accident, as opposed to, 21, excuse me, 12 of 21 patients on the selinexor arm being male. There was also, an imbalance in, good risk carrier type. So one of the most prognostic things about AML is the recurrent chromosomal and molecular abnormalities that come with it. And the European leukemia network has developed a cytogenetic risk score.
And so on the standard of care arm almost half the patients, 43% had good risk profile compared to only 19% on the selinexor arm. On the next slide, is a brief review of the toxicities. Overall, the toxicities were quite comparable and were dominated by the standard of care chemotherapy. The 60 day mortality, which is a commonly used measure in AML for, treatment acceptable toxicity of a regimen was, essentially the same. So 10% in the SONEX or arm and 14% in the standard of care arm, However, there was about a third of patients in the selinexor arm who had, prolonged thrombocytopenia that was transfusion dependent in one patient.
And then, in terms of the AA that most commonly resulted in either holding or dose modifications of the cell and X-ray diarrhea. And then on the next slide is the efficacy summary. And so on that day 14 bone marrow that all patients underwent, half of the standard of care arm had residual disease demostable, whereas only 10% of the selinexor arms did, in terms of the complete remission, 43% of patients on the standard arm achieved a complete remission compared to 76%. And then in AML, as is also the case in myeloma, there's a lot of use of minimal residual disease testing. And so for the 16 complete remissions in the selinexor arm, we were able to get minimal residual disease testing in 13 of 16 or 81 percent of those complete remissions were MRD negative.
And then the overall response rate, which is complete remission plus complete remission with incomplete count recovery, 43% in, the standard of care arm, 86%, in the selinexor arm, And then another important readout for AML clinicians is the number of patients who are able to go on to get an allogeneic stem cell transplant the standard of care arm that was only one patient out of the 7, in the selinexor arm, it was 7 patients out of the 21. The next slide is the overall survival analysis. Obviously, it's a small study. However, despite its small size, There was a statistically significant difference in, median overall survival with the selinexor arm patients having a median survival of 8 39 days or 27 months compared to the control arm, which had a median survival of 265 days, or just about 9 months. And that was statistically significant.
And then the progression free survival also favored the selinexor arm at 5 58 days compared to 108 days. However, this was not statistically significant. And then finally, just to summarize, so this combination of a fixed 60 milligram dose of selinexor in combination with 7+3 was very active in our small study of fit elderly patients and it provided a significant survival benefit despite the small size of the trial, toxicities were quite manageable, with a similar 60 day mortality. And, I feel pretty strongly actually that the 60 milligram dose, is deserving of additional study in larger randomized trials.
Thank you very much. That's our data. It was a terrific terrific summary of your very important study and we're very excited about it as I know you are. I should also add that the early preclinical data with AML showed that selinexor could selectively kill leukemic stem cells, at least in mouse models, and these cells typically are not dividing, which makes them more difficult to kill with standard cytotoxic chemotherapies. Therefore, we may that may partly explain some of the excellent data that we're showing here.
But overall, this is a super exciting study and hopefully can replicate with more patients. Before we move to the question and answer portion of our call. Let me just briefly summarize all that we've reviewed this afternoon. First, it's become quite evident that XPO won over expression plays a key role in cancer development and proliferation. And of course, Espovio is the only approved drug that specifically targets XB-one.
Next, Inhibiting XT-one, either alone or more importantly, in combination with other anticancer drugs, continues to show significant potential across numerous tumor types. We also shared updates from the ASH presentations highlighting the subpopulation analyses from the Boston Stomp and SADAL studies, which provide key insights regarding patient types in combination approaches that may yield the greatest patient benefit. And finally, Doctor. Pardee has just presented new data from a combination study of Xpovio and chemotherapy in a randomized type of study in an older fit population of patients who have AML and further demonstrate the potential utility of XPO Xpovio as a partner for other anticancer drugs. The results that he showed do support the potential future clinical development of Xpovio to treat patients with AML.
With that, now like to turn the call over to the operator so we can begin our Q And A session.
And the first question comes from Brian Abrahams with RBC Capital Markets.
Hey guys, thank you so much for hosting this call and thanks for taking my question. I guess, first off, on the stomp data, obviously, selinexor is showing very nice activity across a variety of different combinations. And I'm curious what are your expectations are for access in terms of reimbursement for use of Xpovio in the earlier line setting within these combinations. Is this something that you think will be accessible, once NCCN guidelines potentially include the Boston data, or do you think that you'll need to complete these, the next wave of studies, including the phase 3 pump study in order to have enabled physicians to have access?
Certainly. Thanks very much, Brian, for that question. If our current experience is any indication, there seems to be little pushback across the country. For the use of Xpovio, even in combination, provided it's in the labeled patient population. The main focus that payers seem to have is to ensure that the patients who are receiving it have met the criteria, that is that they have penta refractory disease.
And in fact, in reality, they actually just ask that the patients have been treated with the major 5 drugs in myeloma before even Exposvio, either with dexamethasone alone or in pretty much any combination. So right now, we are seeing reimbursement and we do know that substantial portion of patients currently receiving Xpovio with Penter refractory disease are receiving it and are having it reimbursed in triplet combinations. If that's the guide and certainly historically with other myeloma drugs that has been the guide, we anticipate that, assuming we have the approval for Boston, which would be for a second line indication, that we could see the use of Xpovio certainly with Velcade easily, but we do expect that will translate into the use of Xpovio with other agents provided the patients have had at least one prior therapy.
Got it. That's really helpful. And then it looks like across the STOMP studies, you're seeing responses with all the different combinations, but perhaps the proteasome combos, maybe have slightly higher response rates versus the image combos. I was wondering if you could comment on that. Is this just a matter of differences in populations across the studies?
Or do you think that there's is there a hypothesis that there may continue to be, I guess, complimentary mechanisms and synergy with the PIs or that, I guess, complimentary talks might enable fuller dosing versus with the image?
Yes, I'll ask Doctor. Barrenson perhaps to comment on that. And then, Doctor. Shaw will also follow-up. Jim?
Yes. I mean, I guess, in answer to the first question, we've used this drug now in many combinations. We've had no pushback from the insurance companies. When using an previously treated patient, we fill the number of priors. Not all of them have failed the 5 in the in the registration.
That's obviously off label use. I'm certainly really curious about whether we can use these drug effectively at lower doses. And that would that's what we observe. And I think that combinations, you may unlock also different mechanisms of overcoming resistance. And we need to learn more about that.
We're doing some studies now with these guys that are supporting, with JAK inhibitors that we hope to get going soon. We've had some really rocket of data. And there's some reasons that that may be a good combination. It certainly seems across the board, kind of like the old days, when I worked with Michael first on Velcade 20 years ago, that you're going to be able to combine this with about anything, and it's going to show activity. And in that regard, we've observed that with VENCLEXTA, for example, a non myeloma approved drug, but we're using it at like 20% of standard doses.
And it's incredibly active when combined with DARRA and or VELCADE, and I think that's really good news for patients because they really want to get good quality. And as we brought this dose down, we're seeing that now. And we're seeing also our ability to manage the side effects as markedly improved And in addition, most importantly, those side effects seem to go away over a number of weeks to several months. They don't seem to maintain themselves. Certainly is not true of some of the other myeloma drugs, particularly the immunomodulatory agents, which seem to get only worse over time.
Got it. That's really helpful. One more go ahead. Sorry.
Okay. We'll just, I guess, we may have had a technical problem. Brian, go ahead.
Oops, sorry. Sorry. One more quick apologies.
Oh, go ahead. Sorry.
No, I was just saying, I agree with Doctor. Barrington said, I think we're activity when we combine with both PIs and Image and even when we look in combination with pomalidomide or lenalidomide, you'll see that the response rates, are we're seeing no other palm combinations or the image, a lenalidomide based combination. So we're seeing that synergistic activity or advertising in combination with image as well. So.
Got it. One more really quick one, if I could just squeeze this in. On DLBCL, it looks like you're seeing effect both in older and younger patients. But I'm just curious, the trend towards slightly lower response rates and higher AEs amongst the older patients, how might that impact the positioning relative to CAR T or some of the other NHL options that the younger patients may have these days? Thanks.
Jaden, can you take that, please?
Yes, no, absolutely. So I think when we look at the responses, physically, they're very similar between the patients that are older above the age of sixty five and younger than sixty five. And I think what this really gives to the point is that there adverse events that we expect to see these older patients are there, but we can still treat older patients with selinexor and they just need that dose reduction or dose modification. And when you provide those dose reductions, dose modifications for those patients, those side effects can be managed. I think it's still a very effective option, even our older patients, that are not going to be CAR T cell candidates or transplant candidates?
Great. Thanks again.
And the next question comes from Maury Raycroft with Jefferies.
Hi, everyone. Congrats on all the progress and thanks for taking my questions. First one is just based on the SPD data. There you're seeing good activity at 60 mgs, but I think there some dose reducing to 40 mgs in the study. And in your phase 3 design, it seems like you might use a 40 mgs cell.
Can you talk more about what you see at 40 mgs in patients and talk about, talk more about the dosing strategy for the Phase III?
Doctor. Jacques, can you take that, please?
Absolutely. So the concept of dose reductions, so yes, so part of the discussions we needed to are exploring 40 milligrams, and so that cohort of patients enrolling is ongoing at this point in time. But I think even those patients with dose reduced from 60 to 40 milligrams, that concept of dose reductions is very, very common across all of our myeloma therapies. And so we think we're in the right spot with the right dose and right schedule. We're just doing a little bit of additional analysis of 40 milligrams.
But I think that we're either 40 or 60 milligrams is what we'll be using in the Phase 2 trial and that concept of those reductions as well established. So that reduction is expecting.
Got it. And maybe one follow-up for Doctor. Barrenson. So We talked to some about the safety profile of selinexor myeloma and how you're getting ahead of managing patients. I guess, can you provide some more perspective on how the AE profile and overall patient experience looks for earlier line patients versus later line patients?
Yes. I mean, I haven't used it really that early. So I can't specifically comment on it, Lea's therapy, but I can tell you that it's like the early days, a lot of these drugs, we've got to kind of get our hands around it. And I think that the responses that we're seeing have been durable when patients are able to go about their lives I think the higher doses were not well tolerated and we certainly are not using those anymore. But the once a week 60 milligram dose, which is kind of our stable has been able to be combined with a multitude of different drugs, even some of the antibiotics.
So we've seen so many years ago with good efficacy. And these are patients that have multiple been multiply treated with multiple PIs and multiple image. So they're not the usual suspects that we go upfront with. So they're very resistant. And I've and that's impressive to me.
I've always been the one is if your drug can overcome resistance or add it to something else. We've been kind of the king of that doing that kind of study. You got a drug, and that's what we're seeing with selling or we're seeing that it can do that. It's a whole new mechanism. And I'm excited to combine it with other drugs that may get repurposed, and we may be able to make Sally work with them.
And I know it's been tried with even things that's disparate, not on label, obviously, as COVID now. And, you know, but in my alone, I think the sky is the limit in terms of combining this thing now.
Got it. Thanks for taking my questions and congrats again.
Thank you. And the next question comes from Jonathan Chang with SVB Leerink.
Hi, everyone. Thanks for taking my questions. This is John Barrett on for Jonathan. Just a couple from me. For Doctor.
Barrison, to start. How do you view SVD as positioned in the 2nd to 4th line, multiple myeloma treatment landscape? And specifically, percentage of your patients do you expect to use the SPD regimen in the second line if Boston were to be approved?
I don't think we know quite yet, and I'm certainly not using a second line today. I guess we'll see of the future comes, but I don't use a lot of imminent upfront. So I think the image are not well tolerated. So I tend to be an outlier. So I tend to use not imminent upfront and then add imminent second line.
So then therefore, I'm more likely to bring the strut 3rd or 4th line because of tolerability issues. I think as I see more data, we may bring this even further up if we see good data combining this with other agents to overcome high risk features. And we certainly know those guys don't do well. But I'm likely to use a third and 4th line. I would probably not much use at second line yet, I would say, yet.
Got it. That's helpful. And for the Karyopharm team, what are the expected benchmarks? I know you mentioned them slightly, but if you could expand on that, for the SPD 031 study and timelines associated with starting enrollment and potential read out of that trial.
Great. And you want to take that?
Yes, absolutely. And so we're just finishing enrollment, to the 40 milligram of selinexor combination with Palmaridamide cohort. With the agency to nail down exactly, which dose will be moving forward and then move forward quickly if not everything else is in place for the phase 3 protocol, in terms of, discussions with the agency, the protocol design, and much of the operational work. So It's, as soon as we complete enrollment of 40 milligram arm, we should be able to rapidly move into the Phase III study early 2020.
Got it. And one more, if you don't mind, for Doctor. Party or for the team, given selinexor's mechanism of action, are there any mutational profiles that would make more sense to pursue in AML populations for example, like TP-fifty three mutation or others?
Yes. I'm happy to answer that one. Initially. So, one particular recurrent mutation that comes to mind and that's been studied a little bit in the preclinical setting is NPM1. Or nucleophosphone 1.
This is a recurring mutation that happens in about 45% or so of AML patients, one of the most common if not the most common mutation. And the pathophysiology involves the nuclear set of plasma shuttling of the mutant protein that's prevented by a selinexor, at least in preclinical models. And so it's a natural potential biomarker for this approach. We did have 4 such patients in the selinexor arm and all of them achieved a complete remission. So I think that would be an obvious sort of low hanging fruit one to go after.
Awesome. Thanks for the answers.
I think the company absolutely supports that. Think it is important to remember, though, that one of the unique things about Xpovio is that by blocking Xp0 1, given that there's approximately 20 major tumor suppressors that even in patients who have mutant disease, we believe we can help overcome that because you can go over and reactivate some of the non mutated tumor suppressors. We saw such an effect in the BOSTON study, Doctor. Shaw mentioned that the hazard ratio for patients with chromosomal abnormalities that is high risk chromosomal abnormalities was quite striking in the BOSTON study despite the fact that we were using such a low dose of Velcade in the selinexor Xplovia Velcade Dex arm. And in particular, the most striking effect was actually in those patients that had lost a copy of the P53 tumor suppress proteins suggesting that this drug really could overcome P53 deficiency and at least in myeloma.
And therefore, we would look at that in other diseases.
Very exciting. Thanks and congrats on the data.
Thank you.
Thank you. And that comes from Peter Lawson with Barclays. Please go ahead, Mr. Lawson your line is live. Alright.
Then I'll move on next to David Lewis with Morgan Stanley.
Thank you very much for taking my question. When you look forward to a potential Boston approval, given that that the really hits the various lines been fairly fluid. Where do you ultimately see the expo via Velcade combination being used mostly? Do you expect it to be primarily in the 2nd line or in 3rd line usage? Yeah, this is Michael, and I'll start and then we can have Jason and Doctor.
Barrenson also comment. So this will probably be fluid as it is for other disorders. 1 can imagine that if a patient received no Velcade in frontline. For example, if they got a Daratumumabrevlumab deck space regimen in frontline, it would make a lot of mechanistic sense to completely switch out. The major mechanisms.
That is to say to move away from a CD38 and move away from an imid, which would leave you with a proteasome inhibitor and Xpovio to be used in 2nd line. Similarly, if a patient, as Jaden mentioned, if a patient received a short course of Velcade as part of an RVD induction followed by transplant. Upon relapse, we show that we had a very potent effect in the second line with, with, exposure of Velcade Dex. Even in the second line, following patients who use, who had limited Velcade exposure, in frontline. So I could see that being used there.
I think for other patients who get full course RVD and frontline followed by say our maintenance, One could imagine that you would want to switch out the proteasome inhibitor on second line and maybe use a different type of regimen, including Daratumumab in 2nd line, and then easily come back in 3rd line to an exovio based regimen. So we do agree that somewhere in the second and third line setting, it would make sense from a mechanistic switch point of view that this would be an effective way to to treat myeloma. Jatin, do you want to comment on Jim?
Yes, absolutely. I think in addition to that, as you mentioned, this is a fluid there's 2 of the key areas where we see it being used, kind of an order lines of therapy and that includes in patients with hydrous disease, I think those patients really need a different mechanism of action. And fundamentally, the way that explovia works really gets to the mood of high risk disease, And so, that's one area where we see this in combination with autism and we know that PIs are the go to therapy in high risk disease. So a nice combination of setting. We can anticipate that being used in earlier lines of therapy for high risk disease.
And the second is in patients with renal dysfunction as well. Again, recognizing that, Fortisna is not really clear and metabolized either either there's also a very much go to drug, in the setting of venable function. This combination makes as I really see that from both high risk patients as well as renal dysfunction. So we see that being used, outside of the typical treatment paradigm can be used only in the second line.
Yeah. I guess I would say that, my likelihood is to use it 3rd line or later given my do things, but that may change with time if we find this as highly effective in those high risk. So the high risk we generally add rutflimid the Ford truck, and maybe we'll be adding Sully, maybe we'll be doing both. I would also chime in, importantly, that this truck is a pill, and that's a major advantage. For patients today.
They really don't want to come to clinic. And I think they've gotten used to not coming with the COVID outbreak. And I think that's a big home run that this drug can be taken orally unlike the PI is accepting 1000 and certainly like the antibodies. And certainly, the CAR T cells, I mean, ease of administration is a key as we have more chronicity to this disease. These patients are living now decades.
Not just years. So things have changed dramatically. They want to be able to go about their life. And taking this drug once a week makes that pretty easy.
Thank you, Jeff. Thank you, Jim. That's great.
Thank you. And next question is another attempt from Peter Lawson with Barclays.
Hi, thanks for taking my questions. Just, I guess, a follow-up for Doctor. Pardy on the NPM1 mutants. If you kind of from that, if you suspect that Sally could also work in the men in MLL rearrangements as well and for the NPM1 mutations with would that be selinexor in combination with something else that you'd have to pursue that?
So the NPM1 mutation is just sort of the lowest hanging fruit because the pathophysiology plays exactly into the administration of, the mechanism of action, excuse me, at selinexor. But, I would agree also with what was said right after that, which is that it it is such a general mechanism, and my own research has shown that you need careful coordination, between the nucleus and other various parts the cell in order to optimally resist chemotherapy in selinexor could, could interfere with that process in a wide variety of mutational backgrounds, including MLL mutated disease. So, you know, MLL rearranged disease is known to suppress P53 signaling. And so, I think you can envision that interrupting the the intra organelle communication in that situation in the face of chemotherapy would be advantageous. And I think that there's agents of many different mechanisms that would likely, synergize with this mechanism of action.
I know there's data out there with some FLT3 inhibitors and also with Bcl-two inhibition with venetoclax. So I think we're many years behind our myeloma colleagues in the use of this drug, but I have every reason to be just as excited about it.
Got you. Thank you. And then just a follow-up question for Michael just around the next steps. I may have missed this, but for SKD and SKR, the next steps there.
Yes, I'll turn that actually over to Jatin, please.
Yes, absolutely. You said SKD and what's the second one? Sorry. I guess SRT. SRT?
Okay, perfect. Thank you. Just want to make sure I got the combination. With SKD, I mean, I think you've seen the data with SKD, we think clearly that's an important, combination that's highly active. So we're discussing various, trials that are in exploration at this point in time with SKD, with I think that clearly the data there shows higher response rates both in len naive patients in relapsing as well as in patients with newly diagnosed myeloma.
And so we're under discussions right now, there's 2 ways of leveraging that information, and the data. And one is, really, I think it speaks to the long term tolerability a number of patients on for 2 3 years with FELI and selinexor and lenalidomide. And so that does then start to raise a question that can this combination be used as an oral therapy a maintenance strategy, given the ability to have long term durability and stay on therapy for long term, it only speaks to both the tolerability and effectiveness of that combination. Deleveraging that strategy, we have an ongoing or just an initiated IST randomized Phase III study of lenalidomide versus lenalidomide plus selinexor as a maintenance strategy done by the SRA and the communal lymphoma group I'm sorry, the SRT date, I think you may leverage to really end up putting, exploring it, the maintenance strategy, kind of thing that's an ideal overall combination. Also starting to explore other combinations in the upfront setting as well, as an IST studies looking kind of build upon the uncertainty backbone.
So to be, to be, a better ongoing at this point in time in this terminal development?
Got you. Maybe if I could sneak in another question, a follow-up question for Doctor. Pate. For the NPM1 mutant patients, if you characterize the additional mutations that they may be harboring, just again, there's often an association with additional mutations for the NPM1. So Just curious about the additional mutations.
Sure. So they tend to co occur with the FLT3 mutations or other signaling pathway mutations like RAS. But then there are also associations with some of the chromatin modifying mutations as well, like DNMT3A. It is, as I mentioned, one of the most commonly mutated genes in AML, so it has several other mutations that it, that it pairs with. But I would say off the top of my head, those are probably the 2 most common are FLT3 and D and M T3A.
Do you know the mutational status of the patients you saw in response system around the NPS-one?
So we have a 42 gene panel that we got on all patients that were enrolled in that study. I don't have that. I can't tell you off the top of my head what other mutations those 4 patients had.
Thank you. And the next question comes from Ed Wright with H. C. Wainwright.
Good afternoon. Thanks for taking my question. So, Michael, this question is for you just to stay on AML. What are the next steps for the company in AML if if anything or are, due to the size of the market, are you prioritizing the other, in potential indications and continuing with perhaps ISTs, looking forward in AML? Thanks.
Yes, let me start and, I'll, and then turn it over to Jatin. I think, importantly, there's a huge unmet medical need Part D mentioned here. And we are really ecstatic about these results. It does look like we've said that Doctor. Part D has figured out a way to appropriately dose selonexor Xpovio in combination with 73 chemotherapy.
And if we could really make this kind of impact, we will find a way to move this forward. One of the other differences between this regimen and some of the others is it permits 2 things. First of all, the Espobio is used in consolidation. So it's not just the 1 or 2 cycles of induction therapy, but also in consolidation. And many of the patients receive consolidation therapy, And he's also exploring the use of maintenance therapy, which would substantially expand the duration of treatment for patients particularly, as MRD takes on more focus going forward.
So we are focused on this. As you say though, we have a lot going on it. And, we do need to prioritize. So in addition to, expanding the size of his own trial, and we'll continue to do that. We are working closely with other groups, and I'll let Jaden talk a little bit about our Krata with the NCI and some of the other plans we have, to expand, in AML.
Doctor. Shah?
Yeah. So much, Michael. Appreciate it. Sorry, let me just highlight the one point here is that we do have an executed creative with the MCI and CTAP. One of the main, cases or areas of these can be with myeloid modem and C, specifically AML and NDS.
And so That's going to be a significant area of interest and focus, working with the cooperative groups and the NCI with Selinexorin, both AML and MDS. And so I think that's the primary focus as we develop and both understand and explore this data and explore the next steps.
Okay. Thank you.
And this concludes our question and answer session. I would like to turn the conference back over to Doctor. Michael Kaufman for any closing remarks.
Yes, thanks very much everybody. It was a lot of data to go through. We really appreciate your attention and interest in Expovio and we think this is just a continuation on what will become a more bigger and bigger application of this unique oral therapy. Thanks very much. And we look forward speaking with you in the near future and special thanks to Doctor.
Party and Barrenson for joining us today. Bye bye.
Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.