Karyopharm Therapeutics Q2 2023 Earnings Call Transcript

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Provided by Quartr
August 2, 2023

There are 11 speakers on the call.

Operator

Good morning. My name is Jason, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics 2nd Quarter 2023 Financial Results 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.

Operator

I would now like to turn the call over to Ellen Webb, Senior Vice President of Investor Relations.

Speaker 1

Thank you, operator, and thank you all for joining us on today's conference call to discuss Karyopharm's Q2 2023 Financial Results and Recent Company Progress. We issued a press release this morning detailing Financial Results for the Q2 2023. This release, along with a slide presentation that we will reference during our call today, are available on our website. For today's call, as seen on Slide 2, I'm joined by Richard, Reshma, Sohani and Mike, who will provide an update on our results for the Q2 and recent clinical developments. Before we begin our formal comments, I'll remind you that 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 as outlined on Slide 3.

Speaker 1

Actual results may differ materially from those indicated section of our most recent Form 10 Q, which is on file with the SEC and in other filings that we may make with the SEC in the future. Any FLS represent our views as of today only. While we may elect to update these FLS 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 FLS as representing our views as of any later date. I will now turn the call over to Richard.

Speaker 1

Please turn to Slide 4.

Speaker 2

Thank you, Elhan. Good morning, everyone, and thank you for joining Karyopharm's Q2 2023 earnings call. Turning to Slide 5, we had a strong second quarter as we accelerate Karyopharm to its next stage of growth with our novel sign compounds selinexor and eltonxor. As Raishma will discuss further, we are advancing a focused clinical pipeline with 3 ongoing Phase 3 pivotal studies. Based upon a strong foundation of supportive data, our recently obtained fast track designation to myelofibrosis and a set of pivotal catalysts over the next 2 years.

Speaker 2

With our current approved multiple myeloma indication in the U. S. With selinexor, we continue to expand and shift into earlier lines. As Sohanyu will discuss further, year over year total demand for EXPOLVIO continues to grow in a competitive multiple myeloma marketplace. Selinexor is also expanding its global footprint with approvals in various indications in approximately 40 countries outside of the U.

Speaker 2

S, providing us with a growing stream of payments from royalties and milestones from our partners as launches move forward globally. As part of our continued prioritization of our late stage clinical pipeline, we have taken additional actions to streamline our operations and optimize our cost structure. As a result, we have reduced our workforce by approximately 20%, which is expected to enhance our financial strength, provide us with the capital needed to deliver on our 3 Phase 3 studies and maximize value for our shareholders. This was an extremely difficult decision given the direct impact this has on our employees. However, after careful consideration, this action was imperative in order to further focus the organization on the near term opportunities ahead of us.

Speaker 2

I am sincerely grateful for the tireless work and commitment of all colleagues for being impacted and to the colleagues that will enable Karyopharm success moving forward. As we move to Slide 6, presented here as an overview of the timing of the upcoming key data readouts, which we expect in 2024 2025. Each of our ongoing Phase 3 clinical trials, if successful, represents an incredibly meaningful growth opportunity for our organization with the potential to deliver roughly $2,000,000,000 in annual peak revenues. Starting with multiple myeloma, A successful Phase 3 trial with SPD anticipated in the second half of next year would accelerate selinexor into the second line treatment and enable continued growth in multiple myeloma. In endometrial cancer, we believe selinexor has the potential to transform the treatment paradigm for TP53 wild type endometrial cancer patients.

Speaker 2

Given the unprecedented data, which was presented at the virtual ASCO plenary series last week of what Jereshma will speak to momentarily. Finally, in myelofibrosis, we recently announced the initiation of our pivotal Phase 3 with the potential to transform the frontline treatment for patients with myelofibrosis as we build upon the rapid, deep and sustained responses we have seen thus far. Collectively, We believe we have the potential to achieve multiple product approvals over the next 2 to 4 years as we deliver our next phase of growth, leveraging our proven and established commercialization and late stage development capabilities. Shifting to selinexor's position internationally on Slide 7, our continued global expansion with our partners provides further opportunities to treat patients in need with selinexor as our partners continue to commercialize and the launch in additional global territories. Our license agreements with our partners provides us with a steady stream of revenues through growing double digit future royalties and potential development and sales milestone payments of up to 400,000,000 Moving to Slide 8, I would now like to turn the call over to Reshma to expand further on our clinical pipeline progress.

Speaker 2

Reshma?

Speaker 3

Thank you, Richard. I want to start off by highlighting our rapidly advancing pipeline on Slide 9, which includes 3 pivotal Phase 3 trials with selinexor that are enrolling in multiple indications of high unmet need. In addition, we are evaluating our second sign compound elpinexor in myelodysplastic neoplasms. As seen on Slide 11, we are Plastic Neoplasms. As seen on Slide 11, we are expanding our multiple myeloma franchise with an important ongoing Phase 3 trial that is evaluating selinexor at the low dose of 40 milligrams in combination with the well established backbone therapy of pomalidomide and dexamethasone.

Speaker 3

Patients with relapsed refractory multiple myeloma who have received an anti CD38 antibody as their most recent therapy are randomized 1 to 1 to the oral regimen of selinexor, pomalidomide and dexamethasone or elotuzumab, pomalidomide and dexamethasone. The primary endpoint is progression free survival. The potential approval of this combination could lead to the only all oral potentially T cell spurring regimen for patients with relapsedrefractory for myeloma. On Slide 13, advanced and recurrent endometrial cancer is the most common form of gynecologic cancer in the United States, with the current treatment landscape primarily consisting of first line chemotherapy with the platinum and taxane. Upon completion of chemotherapy, patients are observed until disease progression.

Speaker 3

This approach clearly needs improvement given that 5 year survival rate in this patient population is only 17%. As selinexor is administered orally And maintenance therapy is well established in other cancer types. We believe Selinexor has the potential to offer a maintenance option in TP53 wild type patients and meaningfully improve the overall clinical benefit for these patients. As seen on Slide 14, endometrial cancer treatment will ultimately be based upon patients' individual molecular classification, including assessment of their microsatellite instability and p53 status. Of the approximately 15,000 patients diagnosed with advanced or recurrent endometrial cancer in the United States.

Speaker 3

Roughly 50% of advanced or recurrent tumors are classified as TP53 wild type. Within this subgroup, 70% of patients are microsatellite stable or MSS and 30% are microsatellite instable or MSI high. The long term follow-up data observed from the pre specified exploratory TP53 wild type subgroup analysis from the SANDO trial, which evaluated selinexor as a maintenance therapy, reinforces our rash now and ongoing confidence in the current Phase 3 EC-forty two trial. Long term follow-up data from the ENDO trial recently presented at the virtual ASCO plenary series on July 25th is seen on Slide 15. With a median follow-up of 25 months for the TP53 wild type exploratory subgroup, the median PFS for The selinexor arm is now 27.4 months compared to 5.2 months in those patients receiving placebo.

Speaker 3

The hazard ratio for the subgroup is 0.42, representing a 58% decrease in the risk of disease progression or death. Patients whose tumors are either TP53 mutant or aberrant and treated with selinexor demonstrated the median PFS of only 4.2 months. These data show that the potential clinical benefit achieved with selinexor is isolated to women whose tumors are TP53 wild type and demonstrate that TP53 wild type has the potential to be a robust biomarker. As we turn to Slide 16, patients with TP53 wild type endometrial cancer were further classified by microsatellite instability status Given the growing importance of this diagnostic marker in endometrial cancer, while potential PFS improvements Regardless of microsatellite instability status, most notable is the signal of a 68% decrease in the risk of disease progression or death, corresponding to a hazard ratio of 0.32 and median PFS that has not been reached in those patients whose disease is p53 wild type and MSS. These data are important given the evolving data observed in the check point inhibitors, which continue to show that the greatest clinical benefit is observed in the minority of patients whose disease is MSI high.

Speaker 3

As seen on Slide 17, we believe that the AE profile of selinexor is generally manageable as a maintenance therapy. The most common treatment emergent adverse events seen in the TP53 wild type exploratory subgroup were nausea, vomiting and diarrhea. And overall grade 3, 4 treatment emergent adverse events were rare with the most common being neutropenia, nausea and thrombocytopenia. No Grade 5 treatment emergent adverse events were observed. Treatment emergent adverse events, incidents and severity were generally similar in the subgroup of patients These tumors were either TP53 mutant or aberrant.

Speaker 3

Turning to Slide 18, given the data we observed in the Exploratory subgroup of TP53 wild type endometrial cancer. We see an opportunity to transform the treatment paradigm for endometrial cancer, given the signal of approximately 5 fold increase in the time to disease progression or death compared to placebo. The data in the p53 wild type MSS is especially notable in light of first line endometrial cancer trials evaluating the efficacy of checkpoint inhibitors. While some of those trials evaluated the efficacy of checkpoint inhibitors in both the treatment and maintenance settings. They demonstrate that the overwhelming benefit is largely observed in those patients whose disease is MSI high.

Speaker 3

Given that 70% of patients whose disease is MSS do not achieve the same degree of benefit with these immunotherapies And in light of the recent approval of dasarlimab in combination with chemotherapy in first line endometrial cancer, whose disease is MSI high, We anticipate that the majority of selinexor will be administered to patients classified as p53 wild type MSS, pending the successful approval of selinexor. This highlights the importance of molecular testing early in a women's endometrial cancer diagnosis as novel therapies transform treatment opportunities for these women. On Slide team are details and are actively enrolling EC-forty two pivotal Phase 3 study, evaluating selinexor as a monotherapy for patients with TP53 wild type, advanced or recurrent endometrial cancer. The study Utilizes Foundation Medicine's tissue based next generation sequence test to identify patients and enroll approximately 220 women whose tumors are TP53 wild types. Patients are randomized in a one to one manner to receive either once weekly selinexor at at a dose of 60 milligrams or placebo.

Speaker 3

Ultimately, this trial will enable the development of a companion diagnostic And we anticipate the approval of a companion diagnostic would occur at the same time as selinexor if approved. The study's primary endpoint is progression free survival with the key secondary endpoint of overall survival. The study is a collaboration between Karyopharm and ENGOT, the European Network for Gynecological Oncological Trial Group and GOG, the gynecology oncology group. Given that this is an event driven trial, we currently anticipate top line data readout in late 2024 to early 2025. Turning our attention now to myelofibrosis on Slide 21.

Speaker 3

We are excited to announce that the FDA has recently granted fast track designation to selinexor for the treatment of patients with myelofibrosis. This designation emphasizes the high unmet need for new therapies and novel mechanisms of action. Given that the efficacy with the current standard of care is limited with less than 50% of patients achieving SVR35 and TSS50. Furthermore, in subgroup such as men and those who start on a low dose of ruxolitinib. Efficacy is even lower with only approximately 25% of patients achieving an SVR35 at week 24.

Speaker 3

On Slide 22, you can see the Phase 1 trial design of our frontline myelofibrosis study, evaluating the combination of selinexor and ruxolitinib in patients with treatment naive myelofibrosis. We presented updated Phase 1 data at the ASCO and EEHA Conferences in June 2023, which can be seen on Slide 23. In the table, you can see that the SVR35 and TSS50 results from 60 milligram selinexor. In the ITT population, the SVR35 rate at week 24 achieved with the low dose of selinexor was 79%. Furthermore, these reductions occurred rapidly with the 71% SVR35 rate observed at week 12.

Speaker 3

At week 24, TSS 50 was observed in 58% of patients. Here as well, you see rapid improvement in symptoms with approximately 67% of patients achieving a TSS 50 as early as week 12. The rapid, deep and sustained efficacy observed with selinexor in combination with ruxolitinib substantially improved the potential benefit that JAK naive myelofibrosis patients may achieve. These data underscore our conviction on our ongoing Phase 3 study as seen on Slide 24 that was initiated in June. The trial will enroll 306 symptomatic intermediate and high risk JAK naive myelofibrosis patients.

Speaker 3

Patients will be randomized 2 to 1 to ruxolitinib plus selinexor or ruxolitinib plus placebo. We anticipate top line results in 2025. Given the important subgroup data in patients who received suboptimal doses of ruxolitinib as presented at ASCO and EHA, We are planning to initiate a Phase 2 trial evaluating selinexor as a monotherapy in JAK naive patients with a baseline platelet count between 50 1,000. This is a uniquely high unmet need patient population with limited treatment options available. This trial will allow investigators to add on ruxolitinib or picretinib at either week 12 or week 24 in the event suboptimal responses to selinexor are observed.

Speaker 3

This trial coupled with the ongoing Phase 3 has the potential to transform treatment of myelofibrosis patients and embed selinexor as a backbone therapy for treatment naive myelofibrosis. With that, please turn to Slide 25, and I will now hand it over to Solania for a review of our commercial performance for the quarter. Thank you, Reshma, and good morning, everyone. On Slide 26, I am pleased to present the progress we have made in our 2nd quarter performance, where XPOVIO continued to show growth year over year in total demand of 9% in a competitive marketplace. In line with our strategy to expand use of XPOVIO in the community setting, total demand grew by 11% year over year in this setting, contributing to about 2 thirds of Exposio's revenues in the Q2.

Speaker 3

We also achieved total demand growth of 6% year over year in the academic setting, driven by use of exovio pre and post T cell therapies. Net revenue continued to be adversely impacted by higher utilization of carryforward, our patient assistance program or PAP, which provides free medicine to qualified patients unable to get financial support elsewhere. This was a result of continued closures beginning late Q1 of many of the 3rd party multiple myeloma foundations that provide financial support to Medicare patients. In the Q2, one of the 4 main multiple myeloma foundations was open for a period of time and continues to remain open. This allowed for a reduction of new patients entering our patients' assistance program, although we continue to see the cumulative refill impact of patients who are already in PAP earlier in the year.

Speaker 3

PAP contributed to 14% of total demand in Q2 2023, which amounted to a roughly $3,000,000 revenue impact. In comparison, PAP contribution to total and was 9% in Q1 2023 and 5% in Q2 2022. Moving forward in 2024, IRA related changes in the design of Medicare Part D will eliminate the patient burden of the 5% beneficiary coinsurance requirement, and we expect significantly less need for Medicare Part D patients to utilize carry forward for co pay assistance. Additionally, net revenue was impacted by 5% higher year over year gross to net in the Q2, driven by increased Medicare and Medicaid rebates as well as 340B discounts. Despite headwinds in the marketplace, we are pleased to see the progress we have made not only in growing total demand for exovio, but also in shifting into earlier lines.

Speaker 3

In Q2 2023, EXPOVIO new patient share surpassed 60% in the second or fourth line compared to 49% in Q2 of last year. Intent to prescribe data showed an improvement in third line use, which continues to support the potential for patients to have a more optimal experience in earlier lines and extend time on therapy. We reaffirm our U. S. Exfoliovo net revenue guidance of $110,000,000 to $125,000,000 in 2023.

Speaker 3

Let's now turn to Slide 27. Amidst an evolving landscape, we believe we're strongly positioned to treat multiple myeloma as a novel class of in the 2nd or 4th line in 3 distinct patient populations. In the community setting where earlier line patients tend to be treated, We believe exprovio is an optimal therapy in the second to fourth line post anti CD38 treatments as a novel class of therapy that is an effective, manageable, easily combinable and a convenient oral therapy. It also has the advantage of decreasing the logistical burden of accessing a hospital for elderly or rurally based patients. In the academic setting, EXPOVIO may be used as an optimal therapy with a novel mechanism of action pre or post T cell therapies.

Speaker 3

As we turn to Slide 28, we're encouraged by the future growth potential of our myeloma franchise. In our SPD study, the triplet combination of selinexor at the lower dose of 40 milligrams with pomalidomide and dexamethasone could lead to the only all oral regimen following an anti CD38 therapy in the marketplace if approved. The partner backbone of pomalidomide is a commonly used therapy in the second to fourth line, generating over $2,000,000,000 in revenues in the U. S. Given these characteristics that make up the SPD combination, We're encouraged by the potential of unlocking significant value to patients with multiple myeloma if approved.

Speaker 3

Shifting to the opportunity in endometrial cancer. On Slide 29, we are encouraged by The potential for selinexor to address a significant unmet need in key molecular subgroups. As we engage with key opinion leaders in this space, it is clear that they see the unmet need for a targeted treatment in unique molecular subgroups, including TP53 wild type tumors. While frontline treatment options are emerging rapidly, A clear unmet need remains in the p53 wild type and specifically MSS subgroup. As we look at the potential opportunity in this large market, endometrial cancer is the most commonly common gynecological cancer in the U.

Speaker 3

S. With over 8,000 patients in the U. S. And over 50,000 globally that have p53 wild type advanced or recurrent endometrial cancer, of which about 70% are p53 wild type MSS patients. We are very encouraged by selinexor's opportunity to help women who need a more effective, targeted and safe treatment option.

Speaker 3

Given that selinexor is being evaluated as a maintenance therapy, convenience is a critical factor. As an oral therapy, we maximize treatment duration by eliminating the need for frequent clinic visits. Turning now to Slide 30. As you heard from Reshma, XP-one inhibition has the opportunity to Form the frontline treatment paradigm in myelofibrosis. There are no other drug classes other than JAK inhibitors approved in the frontline.

Speaker 3

As we look at the potential opportunity in the myelofibrosis market, there are over 4,000 patients in the U. S. And over 26,000 patients globally that are intermediate to high risk myelofibrosis. We are very encouraged by selinexor's opportunity to transform myelofibrosis treatment paradigm. Based on third party market research, about 75% of healthcare providers were willing to adopt combination therapies as frontline standard of care, replacing ruxolitinib monotherapy due to the potential of better efficacy.

Speaker 3

Additionally, there is a strong perception around selinexor in combination with ruxolitinib with approximately 50% of healthcare providers indicating that they would select selinexor plus ruxolitinib as their preferred frontline combination therapy if approved based on promising initial SPR-thirty five and TSS-fifty efficacy rates and a manageable safety profile. As Richard discussed in his opening remarks, Karyopharm has a tremendous opportunity for growth by leveraging our strong commercial team and continuing to build on our base multiple myeloma business with 3 potential launches ahead of us. Please advance now to Slide 31, and I'll turn the call over to Mike.

Speaker 4

Thank you, Sohanya. Looking at Slide 32, we have further optimized our cost structure to focus resources on our pivotal Phase 3 trials and reduced our workforce by approximately 20%, including contractors. These steps further strengthen our financial position to invest in our 3 ongoing Phase 3 studies with each representing a large addressable market with unmet patient needs. Finally, as Richard mentioned, We have the capital needed to deliver on our 3 Phase 3 studies and maximize value for shareholders. Now on Slide 33, I will focus on the quarter's financial highlights.

Speaker 4

Total revenue for the Q2 of 2023 was $37,600,000 compared to $39,700,000 for the Q2 of 2022. Net product revenue from U. S. Commercial sales of XPOBIO for the Q2 of 2023 was $28,500,000 compared to $29,000,000 for the Q2 of 2022. As Sohanya discussed, net product revenue continued to affected by more patients using our patient assisted program as well as higher gross to net discounts.

Speaker 4

Gross to net discounts were 22% in the Q2 of 2023 as compared to 17% in the Q2 of 2022. Turning to costs. With our continued focus on cost management, we are pleased to be delivering a combined 12% year over year reduction in our R and D and SG and A expenses in the first half of twenty twenty three. As we recognize cost benefits from our previous efforts to focus our pipeline, our R and D expenses for the Q2 of 2023 were $31,500,000 down 28% compared to $44,300,000 for the Q2 of 2022. Likewise, we have reduced SG and A expenses in the Q2 of 2023 by 7 percent at $34,500,000 compared to $37,300,000 for the Q2 of 2022.

Speaker 4

Cash, cash equivalents, restricted cash and investments as of June 30, 2023 totaled $237,700,000 compared to $279,700,000 as of December 31, 2022. Based on our current operating plans, We are reaffirming revenue guidance for the full year of 2023 as follows: total revenue in the range of $145,000,000 to 160,000,000 exovio net U. S. Product revenue of $110,000,000 to 125,000,000 With our cost reduction initiatives, we are lowering our expense guidance for 2023. We now anticipate non GAAP R and D and SG and A expenses, which excludes stock based compensation expense to be in the range of 240 $255,000,000 for the full year of 2023, down from our initial guidance of $260,000,000 to $280,000,000 in February.

Speaker 4

And finally, coming to our cash guidance, we have entered into an amendment to our revenue interest financing agreement with affiliates of Healthcare Royalty Partners, extending our aggregate payment amount date by 6 months from December 31, 2024 to June 30, 2025 and increasing the payment cap amount from $1,850,000,000 to $1,950,000 Taken together, our existing cash, cash equivalents and investments as well as the revenue we expect to generate from XPOVIO product sales and other license revenues will be sufficient to fund our planned operations through the end of 2025, excluding the maturity of our convertible bonds in October 2025. I'll now turn to Slide 34 and Richard for some final thoughts. Richard?

Speaker 2

Thank you, Mike. Turning to Slide 35. As we have discussed today, we are rapidly advancing our pipeline, concentrating our investments in 3 Phase 3 programs that are expected to read out through 2024 2025 as we work to create near and long term value for all our stakeholders. I would like to thank our teams who continue to execute in a disciplined manner and who strive each day for patients with high unmet needs. Thank you again for joining us today.

Speaker 2

And I would now like to ask the operator to open the call up to the Q and A portion of today's call. Operator?

Operator

Thank you. We will now begin the question and answer Our first question comes from Peter Lawson from Barclays. Please go ahead.

Speaker 5

This is Shay on for Peter. Thanks for taking our question. So first, just wanted to get maybe a little more color around free drug through the PAP program. I believe this is also an impact in 1Q. So just any color you could provide around how this is compared to 1Q and how you see this dynamic playing out for the remainder of 2023.

Speaker 5

Thank you.

Speaker 2

Thanks, Shay. Maybe for that, I'll turn to Soania to kind of lay out How the patient assistance program in free drug has evolved from Q1 to Q2. So Anja?

Speaker 5

Hey, thanks for

Speaker 3

the question. So in terms of the foundations in Q2, one of the 4 main multiple myeloma foundations was open for a period of time in Q2, which helped to allow for a reduction in patient new starts entering PAP, but we saw continued refill impact in PAP. So PAP contribution in Q2 to total demand was 14% compared with in Q1 was 9%. If you compare it with Q2 of last year At historic normals, it was 5%. So the total net revenue impact from PAP loss alone due to foundation closures in Q2 was roughly $3,000,000 As we think About Q3 and Q4, currently the one foundation that was partly open in Q2 Continues to remain open to date.

Speaker 3

Now we have no line of sight or control into how these funds are disseminated, but our guidance range does Incorporates several factors like GTN impact, but also largely this uncertainty around the PAP impact due to foundation closures.

Speaker 5

Great. Thank you. And maybe just a final quick question is around some of the cost refinements. So I know there is a workforce reduction this quarter. Is there anything the team has been thinking about in terms of whether there may be program refinements kind of later in the year?

Speaker 5

Any other kinds of cost cuttings that we should be thinking about?

Speaker 2

Yes. Thanks, Shay. I think as we have highlighted, we continue on an ongoing basis to make sure we're kind of optimizing and focusing our Our cost structure, so we've continued to do that with the approximately 20% reduction in our workforce this quarter to really ensure we're focused on being able to deliver our 3 Phase 3 programs with our investments obviously in multiple myeloma, Endometrial cancer and myelofibrosis. And on an ongoing basis, obviously, we continue to evaluate our costs to ensure we're really being diligent in our and now we're allocating our call.

Speaker 5

Okay. Thank you.

Operator

Our next question comes from Maury Raycroft from Jefferies. Please go ahead.

Speaker 6

This is Kevin on for Maury. Thanks for taking my questions. Just for endometrial, could you say whether the shift in time line there for the readout. Was that due to competition with PD-1s? And then also, could you talk about the powering for the study and whether you will look at the MSS and MSI high patients as pre specified subgroups within that P53 all type patient population.

Speaker 6

Thanks.

Speaker 2

Thanks, Kevin. I'll turn to Reshma to kind of put all that together and talk about the focus and the progress in endometrial cancer as we advance our EC-forty two trial.

Speaker 3

Hi, Kevin. This is Reshma. So thanks for the question. In terms of the timelines, there's a slight modification from end of late 2024, beginning of 2020 for progression free survival. With that said, we're closely looking at how the data is positively Evolving in this most recent update that Brian Slomovitz presented at the ASCO plenary.

Speaker 3

We now see the median PFS in those TP53 wild type patients evolved from the 13.7 months that we initially disclosed Back in the beginning of last year to now 27.4 months, so more than a doubling in that media and PFS that is going to have a slight impact On how fast those events accrue, taking that into account, we pre project it and anticipate again those PFS events to occur either late 20 24 or beginning of 2025. We're probably looking at approximately a couple of months spread. In terms of looking at the p53 wild type MSS, so great question. And obviously, the data are very encouraging in that subgroup, which does comprise the vast majority of all patients. The way that the EC-forty two trial, the Phase 3 is designed, it's specifically focused on that p53 wild type subgroup regardless of whether MSS MSI and largely because this is a novel subgroup.

Speaker 3

And again, we believe that the data specifically observed in that p53 wild type subgroup Truly is unprecedented. Of course, we will be looking at the subgroup of patients who are p53 wild MSS and separately p53 wild type MSI. But right now, our focus truly is on that large p53 wild type subgroup or patient population, I should say.

Speaker 6

Great. Thanks, Rishma. That makes a lot of sense. And then, just a follow-up on myelofibrosis. We saw that one of your competitors recently top line data, Phase 3 data showing they hit stat sig on spleen size, but not symptom score.

Speaker 6

There's also another update expected this fall. Could you just talk about how you view the evolving treatment landscape here? And then what gives you confidence that you'll be able to succeed on symptom score co primary in your Phase 3. Thanks.

Speaker 3

Yes. So I saw that press release too. I'm not privity any additional data beyond what you saw as well. What I found very intriguing is actually how that ruxolitinib arm Performed, it was actually an SVR rate of approximately 30%, right, which is a little surprising to me lower than what the data that was presented in the COMFORT trial analyzed more than 10 years ago. It really suggests to me that The benefit that ruxolitinib is having on that important spleen volume reduction, probably lower than what we expected.

Speaker 3

When I look at our data from the Phase 1 trial, specifically assessing selinexor at 60 milligrams in combination with ruxolitinib, My confidence goes up given the fact that we saw 78%. So that 78% compared to that 30 ish percent release suggests that we can have a very meaningful benefit on spleen volume reduction in our ongoing Phase 3 study. In terms of the TSS-fifty, so to a certain degree, I'm not that surprised. So my understanding from the earlier transform Phase two trials is that their TSS-fifty was marginal at best. Now, why is it marginal?

Speaker 3

Hard to say, right? We know that a lot of aspects Can contribute to TSS 50 scores, including toxicity, as well as patients not Completing out their form, so missingness in that data. Obviously, AbbVie is going to continue to analyze Their data and hopefully report on more mature data later this year, maybe even beginning of next year. I go back to our data in which we had an opportunity to look at the TSS-fifty data obtained from the patients enrolled as part of that Phase 1. And I'm again very encouraged by the 58% TSS data that we saw.

Speaker 3

Again, compared to ruxolone, which TSS 50s are in the low 40s, it really does suggest that the combination of selinexor plus Ruxolitinib can meaningfully improve both SVR and TSS-fifty, both important endpoints that we need to hit as part of our Phase 3 trial.

Speaker 6

Great. Thank you very much, Reshma.

Operator

Our next question comes from Colleen Kautzky from Baird. Please go ahead.

Speaker 7

Great. Thanks. Good morning and thanks for taking our questions. So in the SIENDO presentation from the ASCO plenary, you continue to see an increase in Fast First Placebo. Can you share what the average time on therapy has been?

Speaker 7

Just trying to think about that in context of the market opportunity for duration in endometrial cancer.

Speaker 3

Yes. I appreciate the question, Colleen. So we haven't reported on that median duration of treatment yet. And it's only because those data are still maturing. We actually still have patients on treatment and as the data continue to mature, we'll have an opportunity to present that median duration of treatment likely at an upcoming presentation in the next 6 to 12 months.

Speaker 3

We do know that median duration of treatment and PFS don't track 1 to 1. However, we are seeing an interesting trend. So as median PFS gets longer, we're also seeing that median duration of Treatment also get longer. So I think that is a very meaningful evolution both from a progression free survival, but time on therapy as well.

Speaker 7

That's helpful. Thank you. And then, congrats on getting the Phase 3 myelofibrosis study up and running and the fast track status there. I know it's early, but how challenging is it to find naive myelofibrosis patients and how many centers do you think you'd target for this study?

Speaker 3

Yes. So, yes, very important milestone to get that Phase 3 initiated. We've got A lot of momentum behind this trial, right. I think again, many of our investigators are very encouraged By the aggregate data that we've been able to present from that Phase 1 trial evaluating selinexor in combination with So let me begin not only the spleen volume reduction in TSS-fifty, but those key aspects that really suggest that the combination is A positive disease modification and this potential monotherapy. So it's this holistic profile that really suggests that this combination can be a game changer for patients who are treatment naive myelofibrosis.

Speaker 3

In terms of competition, well, there is none, right? So there's no other large Phase 3 trials. By and large, this is going to be a global trial. We are activating sites in the U. S, Europe, as well as Asia.

Speaker 3

We're looking at approximately 150 sites. And again, there's really no competition for those treatment naive myelofibrosis patients that are diagnosed throughout the globe. So we're encouraged by the enthusiasm, the lack of competitive headwinds And just really strong support from all of our investigators.

Speaker 7

That's great. Thanks. And last one from us. On the monotherapy myelofibrosis study you talked about on the call, can you just talk about the rationale and why you picked that patient population to look at?

Speaker 3

Yes. So this is a really innovative trial design for us and it's largely based upon This really intriguing finding we've seen from the Phase 1 study, specifically in that subgroup of patients who were treated with suboptimal doses of ruxolitinib, We're finding that patients are still achieving that important SVR35 and TSS50. Again, you don't see that with ruxolitinib alone Really suggest that XP-one is a fundamental mechanism and selinexor potentially has monotherapy activity. So this trial allows us to better investigate that hypothesis. How this trial is going to be conducted is that patients who are treatment naive myelofibrosis, specifically who are have baseline platelet counts of 50,000 to 100,000 Are going to be treated with selinexor monotherapy at either the 60 milligram or 40 milligram doses and that in the event They achieve a suboptimal response to selinexor.

Speaker 3

They have an opportunity to add on either pacritinib or ruxolitinib. Why are we looking at this patient population? Because we know that patients whose baseline platelet counts are between 51100 really has very limited treatment options. By and large, the only therapies available to them are going to be picritinib and ruxolitinib. Despite these therapies, their SVR and TSS-fifty with these therapies are still quite marginal.

Speaker 3

So it's an opportunity to assess selinexor monotherapy and potential these novel combinations too.

Speaker 7

Great. Thanks for taking our questions.

Operator

In the interest of time, please limit yourself to one question. And our next question comes from Chris Raymond from Piper Sandler. Please go ahead.

Speaker 8

Hi, good morning. This is Nicole So maybe just around overall survival in endometrial. So I know that was a secondary endpoint in the SIENDO trial and kind of came up as a topic of discussion during the ASCO plenary session. So I guess I was just wondering if we should expect you to disclose any OS data from the trial in the future. And then just quickly for eltonexor, I know you guys are focused on your late stage programs, but just wondering How you're thinking about the path forward for eltonector and MDS at this point and maybe just how we should think about the prioritization of that program?

Speaker 2

Yes. Thanks, Nicole. Yes, thanks, Nicole. I think as Reshma has indicated, Over the next 6 to 12 months as we continue to see the maturity of the data in the endometrial cancer CEE ENDAL trial, we'll report out on the OS. And maybe I'll turn to Reshma to kind of talk about eltanexor, which obviously is very important for us as we continue to move forward and looking at potential benefit we can bring patients.

Speaker 2

Reshma?

Speaker 3

Yes. Thanks, Nicole. So, eltonexor is one of our 4 core programs. We're specifically evaluating myelodysplastic syndromes neoplasms, specifically relapsed refractory MDS with eltonexor, Very encouraged by the data that we reported from the Phase 2. We'll have an opportunity, in the next few months to really define that optimal development plan specifically with eltonexor in this high risk patient population.

Speaker 8

Great. Thank you.

Operator

The next question comes from Brian Abrahams from RBC Capital Markets. Please go ahead.

Speaker 9

Good morning. This is Joe on for Brian. Thanks for taking our question. With the follow-up data at ASCO, just going back to the endometrial cancer, The follow-up data continue to seem very encouraging. And I know you just mentioned that some patients continue to remain on therapy and continue to show PFS benefit There too.

Speaker 9

So just wondering if there is any expedited pathway for approval and before the top line reads out in late 2024 or early 2025, and we're is this something that you have discussed with the FDA so far. Thank you.

Speaker 3

Yes. Thanks, Joe. So we don't comment on our interactions with the FDA. With that ECL42 remains our opportunity to get both selinexor the drug as well as The companion diagnostic in the form of the NGS platform in which we assess p53 as our approval opportunity in the U. S.

Speaker 3

As well as ex U. S. Too. EZ-forty two is a well designed trial in that we are prospectively evaluating patients who are p53 wild type. It's a well powered study that will specifically allow us to assess That important progression free survival and overall survival compared to placebo.

Speaker 3

So we remain focused on that ECO for 2 trial that is really evolving quite nicely. SIENDO though and the data that we've observed from SIEDO very much is informing informed our design of that trial. We remain encouraged. Those data only increase our confidence And the likely outcome from EZ-forty two.

Operator

Our next question comes from Eric Joseph from JPMorgan. Please go ahead.

Speaker 2

Hi, this is Noah on for Eric. Thanks for taking our question. Just in regards to EC-forty two study, what Median PFS in the placebo arm is anticipated in the for your powering assumptions in your guidance for the readout. And is it similar or more generous than that of the P53 wild type group in the

Speaker 3

Yes. So, it's a great question. So, we haven't disclosed on those kinds of details. With that said, we are assuming A median PFS for selinexor exceeding that 13.7 months, right. So those were the data that we Observed at the time of the initial data cut again in the beginning of 2022, given the fact that median PFS continues to increase quite nicely.

Speaker 3

Again, we're quite confident that that median PFS is going to be in the excess of 13.7 months. It is all of our Phase III trials are well powered, well above that 80%. So again, very confident that at the time that we're able to readout the PFS anticipated end of 2024 beginning of 2025. We're going to see a very meaningful improvement In that PSS with the selinexor treated patients compared to placebo.

Speaker 2

Got it. Thank you.

Operator

And the next question comes from Jonathan Chang from Leerink Partners. Please go ahead.

Speaker 10

Hey, guys. This is Matt Kalper on for Jonathan. Thanks for taking my question. You mentioned there's some enthusiasm around the exovio rux combo and treatment naive mild fibrosis And the data are certainly impressive. I was just wondering, with the upcoming combination readouts and potential approvals there, how does that impact The development and regulatory interactions for your trial given it's only against RUX monotherapy.

Speaker 10

Thanks.

Speaker 3

Yes, we don't really anticipate any kind of impact with either the data readouts, right. Data readout are just the top line results. Obviously, the companies need to go through the extensive regulatory process. We anticipate Our trial to be enrolled or almost close to enrollment completion enrollment by the time that regulatory approval, is obtained again assuming that those data are positive for both SVR and TSS-fifty. So again, we're very confident Not only in the data, but in the design of our Phase 3 trial.

Speaker 10

Got it. Thank you so much for taking my question.

Operator

This concludes our question and answer session. I would like to turn the conference back over to Richard Paulson for any closing remarks.

Speaker 2

Thank you, operator, and thank you everyone for joining our call today. As I indicated at the beginning of the call, we had a very strong second quarter As we continue to accelerate Karyopharm to its next stage of growth with our novel sign compounds both selinexor and eltonexor. And once again, I'd like to thank our teams who execute in a very disciplined manner, striving each day for patients with high unmet needs. And thank you everyone for joining the call today.

Operator

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

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Earnings Conference Call
Karyopharm Therapeutics Q2 2023
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