Karyopharm Therapeutics Inc. (KPTI) Earnings Call Transcript & Summary

Great. Thank you so much. It's a pleasure to have Karyopharm up on stage with It's a pleasure to be back to in-person events. So I wanted to thank everyone for attending and enthusiasm and all your time at the conference. It's impressive to see things turn back 2 years since the last time we've done this conference and for many, it's the first in a couple of years that I want to thank everyone very much. On that, my name is Peter Lawson. I'm one of the biotech analyst at Barclays. I'm the moderator for Karyopharm. I just want to thank, so we've got Richard Paulson, CEO from Karyopharm; Mike Mason, CFO; and we've also got Patricia Judson, Head of Medical Affairs (sic) [ Strategy ]

Strategy.

Strategy. Sorry I can't read my own writing.

No worries.

So thank you so much. And Rich is going to give a 5-, 10-minute presentation just to kind of set the scenes because there's so much that has changed with the company on the positive over the last 6 months or so. So thank you so much.

Thank you, Peter. And it is. You are a tolerant person.

Yes. I should move my camera...

Well, again, thank you, everyone, for joining us. It is great to be back in person and seeing real people. So looking forward to having a great engagement and conversation with regards to Karyopharm. Before we begin, obviously, please see our safe harbor disclaimer and various remarks we make today do constitute forward-looking statements, and actual results may differ materially from those indicated by these statements. So at Karyopharm, we are focused on leveraging the inhibition of nuclear exports. It's a mechanism to treat cancer, and we're the world leaders in that inhibition of nuclear export. We're passionately driven in our mission to positively impact patients' lives and defeat cancer. That's what each and every one of our employees are focused on every day. And to do that, we're focused on 5 key pillars. I think 5 key pillars that drive our underlying value and provide opportunity for what we believe will be substantial future growth. The first pillar is our foundation, and that's expanding in multi myeloma, where XPOVIO is on the market, as you know, where we generated $98 million in sales in 2021. We're striving to become the standard-of-care in second line plus focused on the post-anti-CD38 in the second to fourth line. We're continuing to make very positive evolution, and we'll talk through that as we go through our evolution in '22 and beyond. Also, we're working to expand our access globally with our partners and focused here in the first half of this year to engage with the CHMP to complete our review of selinexor MAA in the second line plus and working towards an opinion again in the first half of this year. Additionally, we're continuing to move forward as you're seeing our pipeline with regards to more trials and expanding new opportunity for selinexor and moving forward with our oral trial with [ Vomalus ] XPOVIO and dex. Second, we're pursuing the development of selinexor in endometrial cancer. We're initiating a registration-enabling study in patients with p53 wild-type tumors this year, and we'll touch on that in a few moments. Third, as you know, we've strategically focused our pipeline over the past year. We'll be focusing in on 4 key areas where we believe our science can have the biggest impact for patients where we believe there's a high unmet need and high probability of success, and that's obviously multi myeloma, endometrial cancer, myelofibrosis and MDS. Fourth, we have strong executive leadership team, which has proven capabilities from an R&D perspective and from a commercial perspective where we continue to build and enhance and deliver in terms of our corporate milestones. And fifth, we are well capitalized to deliver on this with a cash runway through to early 2024. So if you look at our 4 core pillars. Again, we see multi myeloma, endometrial cancer, myelofibrosis and myelodysplastic syndromes, each has a distinct and significant addressable patient population where we believe our medicines hold great promise. If you move and look at a more detailed view of our pipeline, you see our pipeline here, where, in addition to the new plan study in endometrial cancer we're conducting studies, as you know, with 2 front line and second line in terms of myelofibrosis and the same in MDS and moving forward with our XPd trial in multi myeloma. So if we shift to how we've been doing from a performance perspective on the commercial side, we see in the fourth quarter, as you know, we generated $29.8 million in sales, and that was up 47% year-over-year. as we really worked to accelerate growth in the second half of the year. Our net product revenue for the whole year was up 29% for 2021 versus 2020, and we've be doing that as we move forward with our BOSTON approval second line plus and really establishing ourselves in that second to fourth line. We're continuing to increase the breadth and depth of prescribers for XPOVIO and really continuing to see positive momentum in terms of confidence to prescribe by physicians in terms of the intent-to-prescribe metrics. And now if we move forward and look at how we've evolved XPOVIO over the past couple of years. I think it's an important slide to look at because with XPOVIO, we really evolved from the left-hand side from a high dose administered 160 mg per week to lower doses of 60 mg to 100 mg. In the center, you see we've gone from twice weekly to once weekly oral dosing. And on the right, we've evolved from a XX to a XXX in earlier lines. I think this evolution is an important part of many drugs' evolution, and we've done this very rapidly. So we're continuing to build on that and continuing to enhance the ability for physicians to really prescribe with strong supportive care metrics and showing strong data about how physicians can feel confident in the kind of efficacy they're going to achieve if they're looking to dose reduced especially from 100 to 80 in terms of our XPd. So if we turn now to our development programs, first, looking at endometrial cancer. we recently reported top line results from the Phase III SIENDO study where the results, unfortunately, are unlikely to support an sNDA what we generated is a very strong hypothesis generating data with regards to the p53 wild-type population. That was a prespecified exploratory group without Alpha. So we are focused on moving forward, engaging with the agency, engaging with our existing partners and moving forward rapidly in a new trial, which will be registration-enabling. With that trial, it's going to be a trial focused on placebo-controlled, randomized trial in patients again with p53 wild-type. As we move forward with our established partners, we believe we'll get to initiate the study quickly here in 2022 and have the top line data in the first half of 2024. So if we turn to our myelofibrosis programs, where we believe selinexor has the ability and the potential to improve outcomes for patients with the JAK inhibitor refractory disease. And as we know, the only class of drugs in myelofibrosis are JAK inhibitors. And unfortunately, these agents are not curative. About 60% of patients don't respond, Among the 40% of patients who do respond, the responses typically last for about 4 years. There's no other class of drugs approved and the survival is short, typically less than 14 months after patients progress on the JAK inhibitors. Now it's in this class that we've generated very strong data, and this is the data that we reported at ASH '21, and we show that for patients who are on therapy for at least 24 weeks and SVR of 35, 40%. And when you look at SVR 25 achieving 60% to really strong results and compelling, which were extended about moving forward in this patient population. And as you can see, the responses were also very durable with patients being median treatment duration being 11 months from a range of 2.8 to 28.8 months. So based on this data, we've initiated a randomized global Phase II study with single-agent selinexor recruiting patients who had at least 6 months of prior JAK inhibition and randomizing them to once weekly oral selinexor or physicians' choice. 112 patients what we're expecting to recruit in this trial. First patients were dosed in late '21 and top line data from this trial is expected in the second half of '23. So if we turn now to our next pillar, which is myelodysplastic syndromes, where we believe eltanexor, which is our second novel signed compound, has the potential to improve survival in patients with hypomethylating agent MDS, Refractory MDS. Again, there's approximately 15,000 patients who are diagnosed each year in the U.S. with intermediate to high-risk MDS who need therapy. And currently, the only class of drugs approved are the hypomethylating agents. And as we know, once the disease progresses and patients progress on their HMAs, there's no approved therapies and unfortunately, survival is short at 4 to 6 months. In our Phase I study shown here, single-agent eltanexor showed clear activity in patients with primary refractory MDS to HMAs. In the study, we showed a 53% overall response rate, and we showed a median overall survival of 9.9 months, which is very exciting, looking at historical controls of about 4 to 6 months in median overall survival. Recommended Phase II dose of 10 mg eltanexor monotherapy was well tolerated, low incidence in grade of gastrointestinal base and exacerbations of cytopenias occurred in 20% to 40% of patients. So based on this data, we've also moved forward rapidly into a Phase II trial that you see here. In this trial, again, moving forward, our first patients were dosed in September of '21, and we're expecting the top line data from this in the first half of '23. So if we turn now to our financials, cash, cash equivalents, restricted cash and investments as of the end of the year '21 were $235.6 million, which in combination with our revenues from XPOVIO other licensed revenue is expected to give us a cash runway into early 2024. As you know, we've set our guidance for the year at $135 million, $145 million XPOVIO revenue in the U.S., that reflects about 40% growth over '21. We've also set our expense guidance in terms of $2.65 million to $2.80 million as we work to really deliver on our core milestones and deliver on our targeted areas. So as we look forward to this year, the key milestones that we want to deliver on in terms of our 4 pillars are really listed here. Again, in multi myeloma is to continue to grow and to establish ourselves as a standard of care in the second line plus growing the breadth and depth. We're going to dose the first patient in our Phase III study with Pomalyst, and that is going to be happening here in Q1 and also working, as we said, for the first half of the year on the EMA decision on the MAA in second line plus with our BOSTON indication. In endometrial cancer, moving forward rapidly with our Phase III trial in terms of patients bcl-2 wild-type, in fact, this week, kind of tomorrow and Saturday we'll see the results of the Phase SIENDO trial presented. And also, we'll be holding a session on Thursday -- tomorrow to go through the results for all of you. As we look at the top line results, again, in the new trial, we're expected to have in the first half of '24 and move forward rapidly into potential registration. In myelofibrosis, reporting our top line Phase I data in combination with JAKs in treatment-naive, myofibrosis, that's going to be in the second half of this year. And again, in the Phase II, the selinexor in previously treated myofibrosis having that data in the second half of '23. And then in MDS, again, our top line Phase I eltanexor in combination with HMA in the second half of '22, our top line Phase II eltanexor in HMA refractory in the first half of '23. So it continues to be a big year for us. So we're focused on continuing to establish ourselves in multi myeloma and really move forward rapidly with our pipeline across our other 3 key areas. So with that, Peter, let's move into Q&A.

Perfect. Thank you so much you go back to your seat. I guess the first question would be around revenue guidance kind of what gets you that 40% growth? What are the puts and takes that we should be thinking about, whether it's new sites, new accounts, if you can kind of walk through that mix, that would be great.

Yes. So from a revenue guidance perspective, as you know, I mean there's a number of different components that go into it. I think we already have pretty strong breadth of accounts. So we're going to continue to add some new accounts, but our breadth is there. And so within that, we really want to drive the depth. Continue as physicians and accounts have really come on board over the last year as they've started to use us in that second line plus, I think really building on the data we generated data post anti-CD38, really strong data to show them how to manage patients very well, and then just getting increased experience. So our primary growth is going to come from the depth within our existing accounts. And then also, as we move forward, as you know, it's just continuing to grow share. It's continuing to move us up into the earlier lines where we want to be used in that second and fourth line and then it's also to be increased duration as patients are using selinexor in earlier lines we're continuing to see increased duration in those earlier lines. Now of course, within that overall guidance, we all continue to [ hold fingers ] with regards to the evolution of patients being able to get in, patients being able to see physicians. And hopefully, there's no more strong outbreaks as we move forward.

It's in no way a stretch goal. This is kind of a conservative range you're thinking through.

And I think we've said solid guidance, I wouldn't call it conservative I wouldn't call it stretch. I think we've had solid guidance, which we feel comfortable in achieving.

Got you. Okay. And then I guess the biggest prospect that drugs had has been [ cytotek ] profile. How do you change that perception from physicians with -- where [ EDK locals ] that still comes up? So how's that -- how do you do that education?

It takes time. I mean, it really takes time. And again, as we talked about during the presentation, I think the key has been really helping physicians understand the evolution in selinexor. And when you look at the selinexor side effect profile, it really is dose- and schedule-dependent. And so as you know, when it first came to market, got approval. It was 160 mg, twice a week. And it was in late-line patients, fifth, sixth, seventh line patients or tough-to-treat patients. Now where we are, we've evolved it's 100 mg to 80 mg. So it's once weekly. It's a lower dose. We're being used in earlier line patients, which have a better overall outcome. And so it's key I think that we help physicians get that experience. They generated a lot of data which we presented last year where we looked at the BOSTON trial in a number of different ways of data. Also, as you know, we had a trial, our STOMP trial, where we're taking and looking at data with Pomalyst, looking at Kyprolis, looking at dara, a number of agents, which have also been added to NCCN. So as we've done that, I think physicians see the data, they get experience and also done a lot of work with nurses in terms of making sure that they're using kind of a proactive management of patient side effect profile, and we generated data that show as you proactive we manage that. Patients progress very well and are able to tolerate selinexor. So with that, I think our teams have been engaged. It takes time. It takes -- it's impactful being able to engage in person as well, and we have a strong team. We have about 70 people in the field from a commercial perspective who are working to evolve that evolution. And I think as we've talked to kind of one of the leading indicators for that is continuing to see improvements in the intent to prescribe, as physicians become increasingly confident in the profile and the safety and how to manage patients.

Got you. The one thing that's come up from seeing the data was the low discontinuation rate. Is that something that trickles through to the multiple myeloma space where you've got like a 10% discontinuation rate from the endometrial patients earlier use?

I mean I think that was really positive in that trial, but it's just a different patient population, I think different in terms of what combinations because that was single agent versus in combination. Good thing for us in terms of our total development program. That data is very informative, and it helps us understand and I think gives us strong confidence moving forward even as we may look at other areas of gynecological cancer or other areas in terms of single agent. And again, that's at the lower dose. But the lower dose, I think we feel that's the kind of side effect profile we're seeing and the discontinuation rates. Unfortunately, doesn't translate completely over to multi myeloma, because that's a combination data and different patient profile.

Got you. And the cash runway guidance was maintained as early '24 despite, I guess, the pushout commercialization of endometrial. What are the puts and takes that we should think through?

Yes. I'll turn it to Mike for that one.

Sure. I mean we actually did not have any endometrial revenue in that forecast we gave it before. So obviously, we did need to add in the addition of this new study, which we think, again, we're still working on the exact trial size somewhere around $10 million or so. So it doesn't materially change our spend. So we're able to keep that same guidance in early 2024.

It's kind of a shift. So we're engaging $10 million over a couple of years in the trial, but not engaging in the commercial expense front, not engaging some of the other areas we're able to shift those expenses.

Perfect. I'd love to talk about the data that's coming up. So in MF, so we've got the Phase II design. But the Phase I, what updates should we be honed in on in the second half of this year?

Yes. I think when you look at the Phase I data, we are looking to have that data presented and talked to during the second half of the year, probably towards the later part of the second half of the year. And I think when you look at that Phase I trial, obviously, we're working to show and define in the right Phase II dose, a maximum tolerated dose. We're studying 40 mg or 60 mg. And I think what's important in that Phase I, looking at the combo data, is you really want to build on the single-agent efficacy that both agents have. So if they can build on single agent efficacy that both agents have not bring to life increased toxicity, so you're able to use both agents. And I think as we talk to looking at the fact that even those small patient numbers, we were able to see improvements in anemia with selinexor treated patients that -- putting that in combination, I think we should be able to hopefully see positive results in terms of using both agents, not increasing toxicities and hopefully having an additive efficacy data.

And the next picture update, how much data will we see? Is it more patients. It's a lot to even think through?

Yes, a combination of all. So obviously, the focus is on the right Phase II dose, but we are going to have the efficacy data that we generate in that patient population, and we'll be sharing that. I think we recruited -- in the second half of last year, we started recruiting patients into that. So that data, I think, it's recruiting right on track, and we'll see that data readout towards the later part of the second half of this year.

Okay. Perfect. Are there other combination regimens we should be thinking about for MS or you were thinking about?

No, that's our focus right now.

Got you. And then how should we think about potential approval for MF? Is that like 3, 4 years out?

Yes, we haven't given specific guidance on that. But if I look at the Phase II data, which as you know, is in the refractory patients, we're looking to have that data by the second half of '23. So obviously, we've had good engagement with the agency on that while engaging the trial. I think that data continues to hold strong would be very positive, looking to some conversations, which may lead to the opportunity to bring it to patients pretty rapidly, but we've got to see how the data evolves and continue those conversations. And then the Phase I, it's still early. We've got to work through the data, see what the data looks like and then depending on the data and the plan out the Phase II, which is evolving from the Phase I, and then we'll share that as we get more data.

Got you. Okay. And then on your second one of your eltanexor. Kind of when should we expect that date as kind of a first line MDS in '22? Is that kind of a beginning or year-end time or?

Yes. I think it's towards the second -- later part of the second half of the year. Same thing is kind of been recruiting, continuing to look at the right dose and then just the combined ability. And so that made us the same part and same kind of opportunity we're trying to show.

And when we see that data, what kind of -- what should we have to be focused around? Is it in response rates, PFS numbers or...

I think first, obviously, it's going to be the right dose, the safety, the tolerability, that smaller patient numbers. But yes, looking at the response rates, looking at the tolerability and again, I think trying to build on the efficacy of both agents, that's where you want to take both single agents and build on that efficacy and make sure that it's tolerable and patients are able to build on the efficacy of both agents.

Got you. And just on -- seeing I'm just being cognizant of time. So the biggest pushback from the FDA was that the fact that we couldn't -- you couldn't use the wild-type p53, because it was a prespecified exploratory endpoint? Or was it around the p-value for the whole group? I'm just trying to work through?

Yes. I think it's for the p53 population, yes, because it was a prespecified exploratory endpoint. So as we move forward, we have to make sure that we generate the right data for it. We've got to make sure it's a primary endpoint and really used upfront. And then if I look overall at the -- the overall trial as the benefit of 1.9 months in the maintenance setting, just not enough of a benefit in that maintenance setting to really move forward for the broader patient population. So I think we generated a really strong hypothesis with the p53 population, p53 wild-type population. I think -- we're excited to be engaged with the FDA on that and finalizing the trial design. I think what's really positive is, obviously, we have an established network. We know what sites are able to recruit well. We have our partners in place, and so we can move forward, I think, really rapidly engage. And the bottom line for these patients still is that patient's still watching and waiting. There's no therapy for these patients, still. And so we're motivated and excited to move forward quickly and I think build on the strong hypothesis we saw in p53 wild-type population.

Would there been an option -- we're just running out of time. But I guess the final question just on the potential to getting included into NCCN guidelines for endometrial data. Was that ever an option or...

Yes. I mean that's -- we want to -- we're focused on the new study. I think we're focused on the new study and moving forward and generating that data. And as we said, we'll see the data being presented this week in terms of the SIENDO trial. But our focus is really on the new trial, engaging FDA, and engaging our partners and moving forward with them.

Perfect. Thank you so much. This will close the session, but thank you.

Thank you, Peter -- hugging, shaking.

Thank you.