Karyopharm Therapeutics Inc. (KPTI) May 19, 2026 Conference Transcript

...therapeutics, represented by their president and CEO, Richard Paulson, and their CMO, Reshma Rangwala. Richard and Reshma, thank you guys so much for being here.

Thank you for having us, Brian.

There's a lot of data we're going to be looking for in the coming months, so let's dive right into maybe the next data point we're going to see, which is the phase three century data for cell and XOR and MF coming up at the ASCO conference. I know it's going to be, it was accepted as a late breaker presentation. What should we be expecting at ASCO beyond the initial top line data that you presented earlier this year? I know you guys just gave quite a few details, but might we see any more details regarding the death events seen across the treatment and placebo arms where you saw a potential benefit for Selenex? or how much longer will patients be followed up for? What should we be looking for at the conference?

And maybe I'll let Reshma expand on that, but a little housekeeping. Obviously, certain statements we make may be forward-looking statements, so please refer to our most recent 10Q. Reshma.

Really, really excited about ASCO coming up, right? You know, we obviously were selected to break our century results, which is our phase 3 trial evaluating selenixor plus roxalitinib, again, in this frontline population. So think of these patients as newly diagnosed myelofibrosis patients, all of whom have, you know, baseline platelet counts of greater than 100. The top line data, as you alluded to, you know, we went into some detail, right, I think really highlighting the rapid, deep, and sustained SVR35 that we saw meaningful improvements in terms of TSS, which is symptom measurement, you know, at week 24 relative to baseline. And then I think probably and arguably the most intriguing is this promising overall survival signal, again, as early as the data cut off with the median follow-up of about 12 months. Because we're in approved therapy, you know, the safety profiles, while recognized with Selenexor, we didn't identify any new safety signals. I think as going into ASCO, this is going to be the first time the data are going to be presented publicly, especially at a medical congress. And we look to, again, show the totality of data, both from a clinical endpoint perspective, obviously from the safety, disease modification data. What we really want to highlight, and I think John Mascarenas is the key KOL who will be presenting the data on behalf of all Sentry investigators, is to really show how this unique mechanism of XPO1 inhibition really reflects what we see in terms of the SVR35, the VAF improvements, which is just a marker of clonal burden, and then of course this OS. I personally don't think that this is a profile that you would necessarily see with any drug, but it's again very unique to XPO1 inhibition. The OS that you alluded to, absolutely, right? This is one of the first phase three trials that I'm aware of that has shown the signal of overall survival improvement. Again, I don't find it a coincidence that we find it as early as this data cut off. It's very reflective of the mechanism, the rapidity at which the underlying biology is changing with XP01 inhibition. What we put out there was that hazard ratio is 0.43, nominal p-value of 0.0222. While we haven't provided greater clarity in terms of those OS events, what I can say is that it's very consistent with what you would expect from the OS events, right? Progressive disease, toxicity. You would also expect, right, for us to see that kind of signal that your percentage of patients who are progressing and ultimately dying due to PD, AEs, has to be greater in your ruxolitinib or control arm as compared to the combination arm. So, you know, don't want to go into details right now. I don't want to get ahead of ASCO, but, you know, just one way to frame the results. In terms of further maturity, so the data cutoff was February 20th, so just a couple of months ago. So no, we're not going to have another data cutoff. Again, just looking to present the totality of data. Okay.

Got it. And then as these data continue to mature, what do you see as the potential for this early survival signal to develop over time? And is there a certain time point where you believe that will resonate most with both KOLs and regulators? Is it, you know, 18 months, 24 months?

So I think what's really important to keep in mind is that this trial was designed to follow OS all the way until maturity. Right. So it's a double blind trial. Patients as well as the physicians, you know, remain blinded to the treatment arm to which they are assigned. We continue to follow SVR, other endpoints, as well as overall survival, and we'll continue to monitor as those data, you know, get to maturity. Haven't commented on when that next data cut would be, but, you know, again, we want to follow these endpoints all the way out until maturity so we can get a really good understanding of how the benefit, you know, is with the combination relative to ruxolitinib alone. do we have a lot of confidence in the os i do and this really is because we know that svr 35 especially if you looked at the published literature really is a potential surrogate for long-term outcomes so this has been described in phase three trials and meta analyses we've shown this as part of our own century data that svr has this potential predict overall survival So I think the fact that we see over and over, absolutely, it's internally consistent.

How are you guys thinking about engaging with regulators, with the FDA on a potential path forward? What's sort of the gating steps and the key next steps? And do the changes in leadership at the FDA impact your expectation for engagement?

Yeah. So high confidence in terms of the top line results. We expect to gain clarity and provide more clarity around sort of the next steps with the FDA over the course of the next one to two quarters. We don't comment on the individual steps. You know, but again, with that said, we should have clarity over the course of the next six months, if not earlier. The division for, you know, that we'll be reviewing this has been remarkably stable, right? And we know that it's the division that we're going to have our day-to-day interactions with. These are the group of people that we agreed to on the design three years ago before we even started the century. In some cases, they even know Selenexa through our multiple myeloma experience. So they have that historical knowledge of what is the mechanism, why is it important in myelofibrosis. Obviously, they agreed to the phase three trial before we even started it. And we will continue to engage all the way into, hopefully, what is an approval.

Excellent. And then I know there's also the possibility, because it's an approved, Celenex is an approved drug, there's the possibility of exploring a path with regards to NCCN and getting on those guidelines. Just maybe on that, from that standpoint, have you guys received any feedback at this point regarding the potential inclusion of Selle in MF into the NCCN guidelines?

Yeah, Brian, I think as you highlight, you know, the importance of already being an approved medicine is critical here. And we have received, you know, a lot of very positive feedback already from PIN leaders, from investigators, et cetera, around their desire to have us in NCCN guidelines. And I think, as you know, So, you know, to progress with NCCN guidelines, you know, NCCN has different committees. They can meet when they want to meet. They have sometimes planned meetings, other times ad hoc meetings. I think it's important also the level of information. So I think moving forward with our ASCO presentation, I think it will be one key area of input for them. Also, we've been moving forward rapidly to have a publication and a peer-reviewed journal. So that's, you know, very much in progress. and we'll be able to share later more information on that. So I think together that will enable the listing in NCCN. And I think, as you know, there's also a lot of great analogs where products have already been on the market, yet new data, new science. There's high-end met need, as we heard from Reshma. In myelofibrosis, still very much a high-end met need, only one class of therapies. So in those kind of situations and other analogs, You do see with an NCCN listing, products probably reaching about 50% of their peak if you did have a full label, because obviously it's not an area we can actively promote to, but it's an area where physicians can choose to use us, you know, because that's the best interest of the patients and they're wanting to use kind of the best product for those patients.

What does the process look like post-ASCO and potential near-term publication with regards to NCCN guidelines?

Yeah, I mean, it's a process. They can review the data. They get together. It's independent. So it moves forward, I think, pretty quickly. But the committees really own that process.

Okay. And you mentioned 50% of potential peak just from NCCN guidelines alone.

Can you talk about, I guess, the most penetrable initial population that you would foresee with NCCN guidelines and what could payer coverage look like then? yeah so you know i expect it's going to be the combination in this frontline population and i think these are going to be some of the key data that will present at asco is you know looking across the various multiple subgroups patient populations that truly benefit with the combination relative to ruxolitinib i guess i was thinking more like community-based versus academic centers yeah i think early on in in the adoption phase and in all adoptions with new data, you tend to see more of the academics or institutions start to adopt earlier.

And then really your key MF specialists that are also community-based. And then you start to see a kind of broader evolution and engagement across both academics and communities. They use NCCN very much across all different areas of cancer. So I think from that perspective, it's not really a community or an academic perspective. It just tends to be what you see in a typical adoption perspective. So I think that should move forward well. And then from a payer coverage, for sure, NCCN helps to support, you know, very broad payer coverage. We already have well-established capabilities, you know, patient support programs, payer engagement, etc. So I think that should move forward really positively and enable patients to have access.

Excellent. Maybe we could shift gears to another key upcoming data event, which is the phase three endometrial maintenance study. What do you think you need to show on PFS to really differentiate from distalumab in PMMR patients?

Yeah, great question. So, you know, as we look at the evolving landscape in endometrial cancer, you know, by and large, the workhorse has always been chemotherapy, right? So these patients who are advanced recurrent endometrial cancer are going to be treated with chemotherapy doublets, platinum taxane. With the introduction of the checkpoint inhibitors, these patients now have an option to be treated with a triplet, a PD-1 therapy in combination with chemotherapy, and then continue on with their checkpoint into the maintenance setting. Now, despite the fact that the checkpoint inhibitors, and I'm specifically referring to distarlumab and pembrolizumab, have been granted broad approvals, irrespective of MMR status, we know from the data, and biologically this makes sense, that the efficacy is going to be greatest in that MMR-deficient population. These patients comprise approximately 20% of all endometrial cancer patients. Where you see far more modest efficacy is going to be that MMR-proficient population. And to put it into context, the RUBI trial, which evaluated disarlamab in combination with chemotherapy, they performed a post-hoc analysis exploratory in nature that specifically evaluated the efficacy in that P53 wild type PMMR subgroup, call them NSMP. And you see that efficacy from a hazard ratio of only 0.77 highlights the very modest efficacy that you can achieve with the checkpoint inhibitor in that important subgroup. Comprises approximately 50% of all endometrial cancer patients. Our Siendo data, right, clearly has shown substantially better efficacy. You know, my aim, our aim, you know, from the EC042 trial is to show that statistically significant and clinically meaningful outcomes in terms of PFS.

So CELI works best in the patients where there's the biggest on that need, from what we've seen.

So absolutely, absolutely. It's really capitalizing on, So go back to the mechanism. What it's doing is retaining P53 into the nucleus. As an XPO1 inhibitor, we block the efflux of proteins from the nucleus to the cytoplasm. This is very relevant in endometrial cancer. And not surprisingly, it's very relevant in myelofibrosis. So it's not coincidental that we see selenexor activity across these two very disparate cancers. It's actually relying on the same mechanism that's important across the two.

Will you have overall survival data to share or will it be too early?

Yeah. So just like Sentry data, we'll continue to follow OS. We'll have to see, right? Sort of in this patient population, yes, these patients do tend to live very long periods of time. So we'll need to see. At this point, I'm really focused on the top line data. So PFS is a primary endpoint. And then, of course, you know, the top line safety data.

What's your sense as to the awareness, either amongst KOLs and or the community of these phase three results? And where does your feedback suggest as where docs are looking to fit CELI into the maintenance EC paradigm?

Yeah, yeah. Yeah, I think there's a really high level of awareness. You know, fortunately, our Siendil data has been out and talked about quite a bit over the last, you know, two to three years, especially as we've seen the evolution. And I think as Reishman touched on, you know, the checkpoint inhibitors will really see that differential efficacy based on whether it's PMMR or DMMR, and then looking at the P53 wild type population. So fortunately, there's been a lot of good opportunity to present Siendil data to talk to it. Now, you know, molecular classification is standard so in understanding patients p53 or their tumors p53 status is standard and physicians want a medication which they can act on that p53 status so in an interesting way i think it's being kind of fortunate where we now see a lot of desire we just got back and just over a month ago at a major you know guy not conference and you know in talking to the top opinion leaders really a high level of excitement around the data pleased that we're going to be wrapping up enrollment as we just did a couple weeks ago and looking forward to the data so i think from that perspective it has evolved very nicely for us and when you look at where it's going to fit into treatment you know i think reishman just just touched on it is as we see the greatest opportunity to improve on outcomes is that p53 wild type pmr patient and so very clear have that maintenance setting option post-induction therapy. And I think that's something also which the Gynonx are very used to using, you know, establish the induction therapy and then move to the maintenance treatment. And so I think it's a great opportunity for us to really improve outcomes for patients, specifically P53 wild-type driven and this in that PMMR patient population.

And maybe just from an overall relative opportunity standpoint, like how would you characterize the opportunity in endometrial as compared to, for celly, as compared to MF or myeloma?

Yeah. I mean, I think endometrial cancer and myelofibrosis both are very different opportunities than multimyeloma. You know, in multimyeloma, as you know, there's a lot of different treatment options and within that space. And I think when you look at endometrial cancer and myofibrosis, both of them are areas with very few treatment options and the opportunity to really improve on treatment versus current treatments. And so I think both are actually multi-billion dollar market opportunities from that perspective. And then if we think about endometrial cancer and myofibrosis, you know, both of them, we see the majority of patients actually treated in the community. So it's an opportunity, again, for us to leverage our capabilities. And then I think when you look at the endometrial cancer side, as we know, you know, endometrial cancer is most common gynecological cancer. Unfortunately, it's still growing in terms of incidence. So, you know, there's about 17,000 newly diagnosed patients per year. And again, our opportunity is really going to focus on, you know, about 50% of patients at P53 wild type PMMR. So really well defined, clear, and I think an opportunity to drive, benefit to patients rapidly. Got it.

In the myeloma setting, just can you talk about the latest patterns of use that you're seeing and how that's evolving, and then maybe elaborate a little bit more. You talked about the leverageability of the existing infrastructure. I guess, to what degree can your current field force be leveraged for a potential MF and or EC launch? How much further expansion would you look to do?

Yeah, so I think, you know, in the multimyeloma business right now, still we have about 60% of our utilization in the community and about 40% in the academic setting. And, you know, Cell and XOR is very flexible across the whole treatment paradigm, as you know, and I'd say primarily in the community, we tend to be positioned in that second to fourth line post-DERA when you want to get an opportunity to treat with a different class. And obviously being an oral provides a lot of benefit, especially in the community setting where patients may have more challenges with regards to travel or access. In the academic setting, we tend to be positioned kind of parry T-cell engaging therapy. So by specifics, CAR-Ts, et cetera, an opportunity for us really to help, you know, enable different treatment lines, you know, help to preserve the T-cell environment. So within that space, again, we do see the opportunity for continued growth, just given the evolution of the T-cell engaging therapies. When you look at our commercialization capabilities, as we talked about broadly, multimyeloma, MF, and endometrial cancer, in all those areas, the majority of patients are treated in the community. And there tends to be a good concentration in terms of prescribers or some large community groups. So across those areas, we have really good wide coverage. And I think the teams will be able to drive that with approvals in MF and EC and MM. As we get into more of the institutions and academics, as we commercialize myelofibrosis and endometrial cancer, we'd probably look for some targeted expansion to make sure we can have appropriate coverage in the academic centers from a Gynon perspective. And then broadly, what's really positive is, you know, the payer capabilities we have, the access, the patient support, et cetera. All of those we can, you know, leverage across any one of the different disease areas that we have. Also, you know, as we look at the ability to share new data and new science, you know, we have a very strong and well-established medical and scientific affairs group. So they're able to get out and really engage with top opinion leaders and thought leaders on the data, on the science, on the disease areas. And from that perspective, again, I think looking at the opportunity in hematology and then building on that from a solid tumor is what we want to look at doing, especially as we really engage across the breadth of science and help this move forward rapidly.

Good. Maybe last question is in the last few minutes. Now that you've turned over the phase three card in myelofibrosis, I know you have additional assets, particular Elton XOR, that have maybe some different properties, slightly different profile, maybe a different IP as well. What's your latest view on how and where you might consider positioning or developing ELTIN-XR. What are the next steps there, and where can this fit in, if not in other solid tumors, certainly in other MPNs?

You want to see Reshman get excited now, and so the next steps and next futures, Resh.

Yeah. ELTIN-XR is a really exciting second-generation XPL1 inhibitor. Obviously, the targets are the same between Celli and ELTA, But you're absolutely correct. It has slightly different properties, including a lower IC50. And so that lower IC50 just enables lower doses, more chronic doses, chronic dosing. Eltenexor has already been in the clinics. So we've evaluated Eltenexor as part of a larger phase one, two trial. We looked at multiple solid tumors, multiple myeloma again, also looked at it in MDS. But I think, you know, the future lies just, you know, sort of riding on the backbone of where what we saw in myelofibrosis is to look at other NPNs, EV, ET, strong data that suggests that it can have, you know, meaningful activity in those two disease types. You know, looking at other solid tumors, this is where I would love to be able to leverage that P53 biomarker. again, we see something very beautiful in its ability to predict the patients who are going to benefit from XPO1 inhibition. I'd love to be able to look at what other tumors. Can you also see that same ability to predict? And so there's just leveraging basket trials in which we look at P53 status across multiple other solid tumors. So I think that's the tip of the iceberg. I got to start small, but I think that's really where we take our assets next.

And remind us the IP life for that asset.

Yes. I mean, obviously, a lot of work to continue doing on it. We have to look at the development side, et cetera. But if you added a couple of different areas together from a base perspective, it kind of starts in middle 2030s. But, you know, we could probably extend that out nicely into late 2030s. continue to do some work on it, look at what it takes from a development side and as we bring it to market, but definitely will take us to a greater patent perspective than we have with Selenexor, which right now, as you know, with our Polymorph patent, takes us into August of 2035.

Good. Well, a lot to look forward to this year in the coming months, so we really appreciate you being here and giving us your perspectives ahead of that.

So thank you, and thanks everyone. Thanks for having us.