Karyopharm at RBC Capital Markets: Strategic Insights on XPOVIO and Pipeline

On Wednesday, 21 May 2025, Karyopharm Therapeutics Inc (NASDAQ:KPTI) presented at the RBC Capital Markets Global Healthcare Conference 2025. The company discussed both achievements and challenges, focusing on the commercial performance of XPOVIO and its promising pipeline developments in myelofibrosis and endometrial cancer. Despite facing some setbacks, Karyopharm remains optimistic about its strategic positioning and future growth.

Key Takeaways

• XPOVIO experienced a 5% year-over-year demand growth in Q1, despite a $5 million impact due to atypical returns.
• Promising results from the Phase I/II study of selinexor with ruxolitinib in myelofibrosis show a 79% SVR35 rate at week 24.
• The Phase III EC042 trial for endometrial cancer is progressing well, with top-line results expected in mid-2026.
• Karyopharm is focusing on strong commercialization capabilities and disciplined operational expenditure.

Financial Results

• XPOVIO saw a 5% increase in demand year-over-year for Q1.
• The quarter was impacted by a $5 million returns reserve due to atypical high-dose selinexor returns.
• The company anticipates Q1 to be the lowest quarter in oncology, expecting growth throughout the year.

Operational Updates

• Selinexor is being utilized at lower doses (60mg and 40mg) in real-world settings.
• Growth was observed in both academic and community settings.
• The Phase III SENTRI trial for myelofibrosis is expected to complete enrollment by June-July.
• Enrollment for the Phase III EC042 trial in endometrial cancer is on track, with results anticipated in mid-2026.

Future Outlook

• Selinexor is expected to be used both before and after T-cell engaging therapies.
• The SPD trial at a low dose of 40mg is set for a readout in the first half of 2026.
• The company targets all frontline myelofibrosis patients, aiming for comprehensive treatment coverage.

Q&A Highlights

• Karyopharm is using absolute TSS as a more sensitive endpoint in its myelofibrosis trial.
• There have been no changes in regulatory perspectives under the new administration.
• All myelofibrosis Phase III patients are required to take dual antiemetics.
• Approximately 75% of physicians are open to adopting doublet therapies addressing key disease hallmarks.

For a more detailed understanding, readers are encouraged to refer to the full transcript of the conference call.

Full transcript - RBC Capital Markets Global Healthcare Conference 2025:

Brian, Tech Analyst, RBC Capital Markets: Tech analysts, here at RBC Capital Markets. Our next presenting company is Carrier Pharm Therapeutics, and we’re really pleased to have their president and CEO, Peter Paulson, and their CMO and head of research, Rishma Ranvala. Richard and Rishma, thanks so much for joining us.

Peter Paulson, President and CEO, Carrier Pharm Therapeutics: Thanks for having us, Brian.

Brian, Tech Analyst, RBC Capital Markets: So I know there’s a lot to talk about on both the commercial and pipeline front, but maybe we can start with commercial and XPOVIO. Can you talk about some of the quarter over quarter dynamics you’re expecting for XPOVIO this this year that’s gonna enable you to get to your guidance and sort of what’s what’s gone into your guidance? What’s shaped that in terms of your expectations for overall commercial penetration of Dynamics?

Peter Paulson, President and CEO, Carrier Pharm Therapeutics: Sure. So I think as we’ve, you know, just shared on our Q1 call, in Q1 year over year, we delivered 5% demand growth, and our Q1 was impacted in our returns reserve by about $5,000,000 and it’s kind of atypical returns of high dose eighty and one hundred milligrams selinexor. And, you know, that was really related to a large batch which was produced to support the BOSTON trial and the label, which came to fruition in the end of twenty twenty. And then as we’ve seen selinexor in the real world, we’re seeing selinexor being used much more at the lower dose of sixteen forty. So, you know, the return window opened, and we had return, you know, kind of atypical return of about $5,000,000 And that’s really a onetime impact, Brian.

So I think our focus, you know, we know moving forward, real world purchases, real world utilization, the production that we do is really targeted towards that sixty and forty, so we don’t see that occurring moving forward. So I think our focus moving forward is to continue working to deliver demand growth. I think, again, in Q1, the 5% year over year demand growth, we saw growth in both the academic setting and in the community setting. And it’s important because there’s very different types of care that are utilized in the two settings. You have the majority of multiple myeloma patients which are being treated in the community.

And in the community, you know, selinexor is positioned in that second to fourth line, really post anti CD38, which are used, you know, increasingly in the first or second line. And I think what, you know, the community physicians like a lot about selinexor is it’s flexible, it can be used in oral, and it’s enabled across kind of the treatment paradigm. So from that mechanism, we’re working to make sure we continue driving that utilization in the community setting, and community physicians are very comfortable having to use the dual antibiotics for a couple months, enabling patients to really benefit from selinexor, depending on where they are in their treatment journey. And then in the academic setting, we’ve returned back to growth last year, and that’s really around all the engagement for T cell engaging therapies. So you’re seeing, obviously, bispecifics, CAR Ts, etc.

In those settings. We generated a lot of data over the last couple of years to show that selinexor doesn’t negatively impact the T cell environment. International Myeloma Working Group put a lot of work together and issued some guidelines, you know, towards the beginning part of this year, really, again, stressing the importance of sequencing, kind of strategic sequencing, before you’re using the T cell engaging therapies. And in there, selinexor comes out as an agent that they’re recommending to be used pre post T cell. So I think, again, we’re going to continue to see that utilization grow, and that’s our focus within those two paradigms.

As we know, kind of moving through the year, Q1 typically in oncology is kind of your lowest quarter, and continues to evolve nicely during the year, we expect to see that moving forward.

Brian, Tech Analyst, RBC Capital Markets: Great. And kind of your outlook from the myeloma indication longer term, I mean, you kind of alluded to some of the growth drivers. Can you maybe elaborate a little bit more on sort of where you see the most potential for growth to pick up?

Peter Paulson, President and CEO, Carrier Pharm Therapeutics: Yeah. I think really continuing in those areas. As we said, you know, we have nice data and continuing to do data with regards to the academic and community setting around T cell engaging therapies, as, know, those will continue to be used broadly in those areas. They’re starting to move up into some earlier lines. Again, what’s that sequencing pre?

What’s it post? That’s going be critically important, and we’re going to continue to be used in those areas. We have some nice data being generated with mozignomide, which we know, you know, is working and coming to market, you know, over the next couple of years. Again, in that area of T cell engaging therapies, think looking at that being used potentially post some T cell engaging therapies. We have our SPD trial at the low dose of forty milligrams, which we’ll be, you know, reading out in the first half of ’twenty six.

So again, generating more data showing, as we showed, you know, initially last year from that trial, forty milligrams, much improved toxicity profile. Patients were able to really get a nice benefit, and I think, again, that’s going to continue to drive our utilization in the community setting in the earlier lines. Okay.

Brian, Tech Analyst, RBC Capital Markets: Great. And then maybe we can move to some of the next indications for selinexor, maybe starting with myelofibrosis because I know we’re gonna be coming up on on some some data fairly soon. You’ve shown some early promising data in the in a phase one, study for for the drug, in in combination with ruxolitinib in frontline myelofibrosis. Can you talk a little bit about those dataset? What gives you the most confidence in the phase three readout from those data?

And maybe talk about what you’re seeing as the study has continued, as patients continue to be dosed in terms of durability and how we should contextualize that, with with what, what we would expect from ruxolone historically. And I know we’ve seen some pretty recent follow-up data. I think it was in right around your first quarter earnings press release. Maybe you could talk about that as well.

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: Absolutely. So, obviously, really, really excited about our myelofibrosis opportunity. We do have an ongoing phase three trial. It’s known as the SENTRI trial that is evaluating in a double blind setting the efficacy safety of ruxolitinib at selinexor sixty milligrams versus ruxolitinib alone. That trial should be completing enrollment very soon in that June, July time frame.

Now to your question, a lot of you know, this trial was based upon, an earlier dataset, specifically a phase one two study that evaluated the efficacy and safety of selinexor plus ruxolitinib in this JAK naive population. And despite the fact that we’ve been studying myelofibrosis for over seven years, right, I think these were the data that really entrenched our belief of the benefit that selinexor can provide in arguably this hard to treat patient population that doesn’t have a lot of options in which to get treated. When we looked at the efficacy, right, that SVR 35 at week twenty four was seventy nine percent. Now compare this with ruxolone in a similar patient population. SVR 35 rates for ruxolone, less than half at maybe thirty, thirty five percent.

So a really remarkable increase in those overall rates. Now in parallel, we also saw very meaningful improvements in terms of symptoms. Right? And we’ve looked at symptoms two different ways. TSS fifty, which was the traditional endpoint in myelofibrosis, but also absolute which is a more sensitive method of assessing that symptom improvement over the course of this.

When we look at that absolute TSS data, it really shows a very, I think, remarkable 18.5 movement at week twenty four relative to. So when we look at the SVR thirty five, that TSS, again, that 18.5 compared to ruxolitinib, maybe 11 to 14 points based on recent data, it really suggests that we can we can maximize both SVR 35 rates, which is spleen volume shrinkage, as well as very meaningful symptom improvement. Now to your point, both of these endpoints are just assessed at week twenty four or six months. What this patient population really wants to appreciate is that once they achieve benefit, they’re gonna stay in benefit. So we looked at that durability of response.

There are two really, I think, encouraging data. When we looked at these data and presented it last year, what we found is that patients who achieved either an SVR 35 or a TSS 50, they remained in response. It was a one hundred percent durability of response, again, for both SVR 35 and TSS 50, responders. So we got the improvement. We’ve got the durability.

Safety is also evolving very nicely. Right? The low dose incorporation of the dual antiemetics both from a heme as well as non heme perspective. That safety, again, profile is evolving very nicely. Good.

The new data that we presented, and I just wanna touch upon this very quickly, was from a completely different dataset. Right? So this dataset was specifically evaluating selling monotherapy in a large patient population. This is selling monotherapy, this heavily pre exposed, high risk population, and what we demonstrated is that selinexor is impacting all four hallmarks Right? So we see this very meaningful SVR reduction.

We’re seeing very meaningful symptom improvement. We’re seeing really intriguing hematologic improvements as well, specifically anemia. So hemoglobin levels are stabilizing. We’re seeing this cohort transfusion burden is lower as compared to the physician’s choice arm. And lastly, we’re seeing really exciting disease modification.

That disease modification in terms of lower cytokine levels that drive many aspects of this disease is occurring as fast as before, so we’re really seeing, you know, just remarkable data. These data are just the most recent data that demonstrates selinexor is active in this myelofibrosis population.

Brian, Tech Analyst, RBC Capital Markets: Great. And how has the phase three been going? What’s the latest feedback you’re getting from principal investigators, third party CROs, the overall study conduct? How are you feeling about the way enrollment’s gone, conduct’s gone?

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: We’re we’re really excited here. You know, I think we’ve got, you know, KOLs from all of our academic sites in The US as well as US that are participating in this trial. They are clamoring for new therapies in myelofibrosis. Right? Standard of care has been ruxolitinib for over a decade.

And, yes, right, it has provided some degree of spleen volume reduction, some degree of of symptom improvement, but I think everybody appreciates that benefit is still quite modest and is really only impacting a very small patient. So we need new therapies to really provide benefit to a much larger group of patients. So they’re really excited. We see that, you know, translate to enrollment. I think the other aspect is that they’re really pleased, right, that we’ve been able to evolve this symptom endpoint from TSS 50 to absolute TSS.

It’s just perceived as a more sensitive way of detecting that symptom improvement. So, yeah, we’ve got we’re really excited about what the next six months holds for us.

Brian, Tech Analyst, RBC Capital Markets: Can you talk a little bit more about that endpoint change and maybe a little bit of background on sort of what had catalyzed it, the change to absolute TSS, the receptivity that you’re getting both from regulators and from clinicians on that change? And I know I think you’re also there’s updates that exclude fatigue in the TSS calculation as well, sort of how that plays in? Because I think that’s important because I know the previously, TSS 50 has been a challenge for other developmental programs. And just kind of curious kind of the engagement and buy in of the community and regulators for this change.

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: Yeah. Yeah. So, to step back here, so when we talk about TSS 50, absolute TSS, it’s important to remember the raw data is absolutely the same, right? So, everybody fills out, every patient fills out a form called the MFSAF form, and they fill it out daily. The endpoints, right, the TSS 50 versus absolute TSS, all it does is just analyze the data a little differently.

Okay? So TSS 50 is just looking at that week 24 endpoint, that time point, comparing it to baseline. Absolute TSS is actually leveraging all of the data that has been collected over this one point, six six months and then averaging the benefit relative to baseline. Because you can leverage that twenty four week or six month data, it’s just perceived as a more sensitive way of detecting that improvement above and beyond ruxolitinib. That’s the key point.

To your point, Brian, TSS fifty has dogged multiple trials. Right? I mean, how many phase threes have we seen in which TSS fifty has missed? Right? Absolute TSS has gotten a little bit closer, and I think we have a huge opportunity to now really be able to demonstrate that meaningful symptom improvement by using this absolute TSS endpoint.

There’s been a lot of positivity around this. Right? Okay. Investigators I already talked about, advocacy are really excited about this evolution because it’s just an easier way to explain this improvement to patients. Right?

What they want to be able to tell them is that, yes, you know, you can experience some degree of improvement above and beyond ruxolitinib. It’s just an easier way to explain it. FDA as well, regulators. I think they’ve also appreciated TSS fifty, while it served its purpose for the original trials, it’s just not sufficient when you’re going up against an act of control. So, a lot of agreement.

Right? Including

Brian, Tech Analyst, RBC Capital Markets: the new FDA, new administration leadership?

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: Nothing’s changed. Nothing’s changed.

Brian, Tech Analyst, RBC Capital Markets: Nothing’s

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: changed, you know, under the new administration.

Peter Paulson, President and CEO, Carrier Pharm Therapeutics: And, Raishma, maybe just talk to the fatigue. Yeah.

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: Yeah. The fatigue aspect, so this isn’t new for us.

Brian, Tech Analyst, RBC Capital Markets: Yeah.

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: Right? And it’s not new for myelofibrosis. Reason I say this is that going back to the original COMFORT and Jakarta trials, that led to ruxolitinib, fedratinib. They excluded fatigue. Right, from their TSS 50 analyses, and largely did it in agreement with the FDA because it’s such a challenging endpoint to really assess improvement.

So they excluded it, something that we’ve done from the very beginning of our myelofibrosis program, something that’s going to be done in our phase three as well.

Brian, Tech Analyst, RBC Capital Markets: Got it. One of the biggest questions we get asked about with regards to selinexor is on the drug safety and tolerability, and I know you’ve done a lot of work to optimize dosing and ancillary medications like antiemetics. Can you talk about how that’s being incorporated into the Phase III? What you guys are seeing in the study in terms of how much antiemetic use there’s been? And is there any concern that the use of antiemetics across all patients may actually mitigate the ability to demonstrate a delta on symptoms, if you’re sort of helping alleviate some of the symptoms on the rux placebo patients as well?

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: Yeah. So great question. So, you know, we have a lot of experience with selinexor going all the way back to our multiple myeloma days. Nausea and vomiting, known side effects of selinexor. We know that there are two drivers to really mitigate against nausea and vomiting, lowering the dose and incorporation of dual anti emetics.

So all of the patients in our myelofibrosis phase three, as well as our other phase threes, including endometrial cancer ECL42, as well as the multiple myeloma trial, must take dual antiemetics, the two antiemetics prior to each dose for the first two cycles. This is really easy for these patients. Right? It’s really easy. It’s easy to prescribe.

Compliance is extremely high in our phase three. It’s a greater than eighty five percent. We also see that translating to an improved GI profile, lower rates and grades of nausea and vomiting. And the reason I can say that is, again, going back to this dataset, this new dataset that we just presented a few weeks ago at our earnings call, nausea rates with patients treated with celi alone were as low as thirty three percent. Right?

These patients were also treated with dual antiemetics. So we see this really nice evolution

Brian, Tech Analyst, RBC Capital Markets: in

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: terms of lower grit rates and Okay. Of nausea with antiemetics.

Brian, Tech Analyst, RBC Capital Markets: Okay. Talk about the MF opportunity. Where do you see this potentially fitting in? Is this something you would imagine all frontline patients would take or patients maybe who have specific issues in terms of extremely large spleens or symptoms? And how are you leveraging your existing infrastructure from a commercial standpoint to as you think about anticipating the launch?

Peter Paulson, President and CEO, Carrier Pharm Therapeutics: Yeah, Brian. I mean, Raishman just touched on and you mentioned, we are targeting all frontline patients, really all JAK naive patients, very consistent with with what ruxolitinib has has been targeting. Obviously, patients quite much greater than hundred thousand. And within that population, you know, there hasn’t been any evolution in terms of frontline sanitary care for thirteen years. So, you know, as as Raishma just touched on, the opportunity to more than double the response when you look at SVR thirty five, When you look at all four key hallmarks, SVR symptoms, you know, anemias, hemoglobins, and disease modification, think it’s an incredible opportunity to really add on to the standard of care, which has done a wonderful thing for patients.

But adding on to the standard of care, I think, makes it a very easy and convenient opportunity for uptake with physicians. You know, our our commercial infrastructure is strong. We already have, you know, strong commercialization capabilities from medical affairs perspective, from an access and reimbursement perspective, and from a sales and marketing perspective. And the majority of myelofibrosis patients are actually treated in the community. So we have about an eighty percent overlap already with the majority of prescribers, so we’re able to commercialize rapidly with a lot of synergy.

And, you know, in some market research we’ve done with physicians, we see, again, there’s a significant unmet need, and research shows that about seventy five percent of physicians would be adopting doublet therapies that address all these key hallmarks of the disease really rapidly to help improve outcomes for patients. And I think the other key area that we’ve seen in our data is that selinexor works across all subgroups of patient populations. So the opportunity to really address a wide swath of kind of on target patients and to build, I think, on the durability component that Reshma touched on. Right now, in the real world, I think when you’re looking at ruxolitinib, you have about twelve to thirteen months’ worth of therapy in the real world. If we have good durability, I think we can build on that And again, deliver benefits for patients and rapidly commercialize.

Brian, Tech Analyst, RBC Capital Markets: Great. I know we’ve only got a few minutes left, but I definitely want to touch on the endometrial cancer program for selinexor. Can you talk about how that Phase III is going, kind of your level of confidence in terms of potential timelines there and where you see this potentially fitting in an evolving landscape? I know it’s a little bit of a slightly more complicated landscape than MF, but just kind of where you see this ultimately fitting in where the biggest pockets of unmet need are going to be.

Rishma Ranvala, CMO and Head of Research, Carrier Pharm Therapeutics: Yeah. Another really exciting program. We have an ongoing phase three, as mentioned, the phase three EC042 trial. This is leveraging a biomarker, so specifically p53 wild type, which is observed in over half of all patients with advanced recurrent endometrial cancer. And based upon the data from an earlier phase three, we really demonstrated some really interesting efficacy with selinexor specifically in that subgroup of patients whose, again, tumors are p53 wild type.

This ongoing phase three is enrolling patients who are p53 wild type. To your point, though, I think the greatest opportunity is really going to be those patients whose tumors are a p53 wild type and NFR proficient. That group of patients is also very sizable, of around fifty percent of all patients, and they remain, right, really that unmet need population. And I say that because, yes, there has been introduction of new therapies, specifically the checkpoint inhibitors, teplizumab, dostarlimab, for all patients. But what we see when we really interrogate the data is that the benefit with the checkpoint inhibitors, that MMR proficient subgroup, is really modest.

Right? EFS is only ten to thirteen months. This includes that induction chemotherapy, and the benefit that we are seeing of forty months actually exceeds the overall survival that they are seeing with the the checkpoint inhibitors. So really driving that benefit in that, again, high unmet need subgroup enrollment is going really well. So, you know, we anticipate being able to complete enrollment, you know, sort of over the course of the next few months, and top line results likely in the middle of twenty twenty six.

Brian, Tech Analyst, RBC Capital Markets: Great. Good. And just before we wrap up, last question. Can you talk about how your kind of bigger picture staying disciplined with your OpEx and some of the key steps that you’re taking to support operations into the phase three MF readout?

Peter Paulson, President and CEO, Carrier Pharm Therapeutics: Sure. I mean, we’re saying very disciplined, right? So we’re very focused and have put efforts in place over the last couple of years to really ensure our focus is on the phase three readouts. So we don’t have any other programs running. We’ve shut down, you know, all kind of previous programs and are supporting a profitable commercial multi myeloma business and very targeted on delivering the phase three programs, you know, as we move forward.

And I think as Reshma touched on, we’re really focusing on how do we make sure we have great clinical trial execution, a great quality in our work in helping to identify the right patients, making sure, you know, we’re on top of having the dual antiemetics used for the execution. And then as we go through that and roll through, you know, being able to read the data out quickly and hopefully positively is critically important. It’s what the organization is focused on, and it’s a super exciting time, you know, with these major readouts right in front of us and being transformational when you look at myelofibrosis and endometrial cancer, of building on the foundation we have in multiple myeloma.

Brian, Tech Analyst, RBC Capital Markets: Great. Well, thank you guys so much for for being here, and thanks, everyone, for joining us.

Peter Paulson, President and CEO, Carrier Pharm Therapeutics: Thank you, Brian.

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