Karyopharm Therapeutics (KPTI) Q2 2024 Earnings Call Transcript

Karyopharm Therapeutics (KPTI -3.56%)
Q2 2024 Earnings Call
Aug 06, 2024, 8:00 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good morning. My name is Carolyn, and I will be your conference operator today. At this time, I would like to welcome everyone to Karyopharm Therapeutics second quarter 2024 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. I would now like to turn the call over to Elhan Webb, senior vice president, investor relations.

Elhan Webb — Senior Vice President, Investor Relations

Thank you, Carolyn, and thank you all for joining us on today’s conference call to discuss Karyopharm’s second quarter Q2 2024 financial results and recent company progress. We issued a press release this morning detailing our financial results for Q2 2024. This release, along with a slide presentation that I 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, Sohanya and Mike will provide an update on our results for Q2 2024 and recent clinical developments.

Before we begin our formal comments, I’ll remind you that various remarks will make today constitute forward-looking statements, FLS for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on Slide 3. Actual results may differ materially from those indicated by this FLS as a result of various important factors, including those discussed in the Risk Factors 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. Please turn to Slide 4.

Richard Paulson — Chief Executive Officer

Good morning. Thank you, Elhan, and thank you all for joining us today for Karyopharm’s Q2 2024 earnings call. Turning to Slide 5. I would like to first focus on our innovation and growth strategy as we work to deliver our next stage of growth by advancing our late-stage pipeline while continuing to strengthen our foundation in multiple myeloma.

Starting with myelofibrosis, we are more excited than ever regarding SELINEXOR’s potential opportunity in this indication. Physician interest in enrolling patients into our Phase III study is strong and the competitive environment continues to evolve favorably for us. Building on our strong clinical data, the new preclinical data that we presented at EHA further reinforces the role that SELINEXOR might play in myelofibrosis. In endometrial cancer, we presented updated data at ASCO, demonstrating nearly 40 months of progression-free survival when SELINEXOR is used as a maintenance therapy in patients whose tumors are TP53 wild-type/pMMR.

This population represents approximately half of all patients who are diagnosed with endometrial cancer. It is noteworthy that the progression-free survival that SELINEXOR is demonstrating in the maintenance setting in this subgroup exceeds the overall survival that is achieved by the checkpoint inhibitors in patients whose tumors are CMMR. As we continue to enroll patients in our EC-042 Phase III trial in endometrial cancer, we are also confronting the complexities of a molecularly targeted maintenance trial and are taking proactive actions, both of which Reshma will expand on. As a result, we now expect to deliver top line data in early 2026.

In multi-myeloma, we are pleased to report our second consecutive quarter of growth in XPOVIO revenue, giving us confidence to raise the low end of our revenue guidance for 2024. The importance of XPOVIO’s differentiated mechanism of action, its all oral administration and potentially T cell sparing impact is increasingly resonating with community and academic physicians, which Sohanya will expand on. As we work to build on our commercial foundation of multi-myeloma, we expect to leverage our positively evolving SPD data at the 40-milligram dose to update the design of the Phase III EMN29 trial, which will include targeting fewer participants for enrollment and lowering the projected cost of this trial. Finally, in light of our strengthening commercial performance, disciplined cost management and focused approach to clinical development, we believe we’re in a strong financial position to deliver on our prioritized late-stage pipeline.

Mike will expand on our lowered 2024 R&D and SG&A expense guidance. We continue to be very optimistic about our next stage of growth and are well positioned to capitalize on the opportunities for SELINEXOR with our diversely built late-stage pipeline across three different cancer indications. We continue to believe the annual peak revenue opportunity for SELINEXOR could be $2 billion in the U.S. alone.

I would now like to turn the call over to Reshma to expand on our recent data announcements and discuss our progress with each of the programs in our pipeline. Reshma?

Reshma Rangwala — Chief Medical Officer and Head of Research

Thank you, Richard. Turning to Slide 7. I’d like to highlight our promising late-stage pipeline led by SELINEXOR’s three ongoing Phase III studies, each of which has the potential to enable a new standard of care, continuing to build upon the growing body of data and utilizing the once-weekly lower doses of either 40 or 60 milligrams. We continue to be very encouraged by the data generated to date supporting our three pivotal Phase III trials, including the improving long-term follow-up data in endometrial cancer from the exploratory subgroup analysis in the SIENDO trial that was presented at ASCO, which I’ll expand on shortly.

Starting with myelofibrosis on Slide 9. We are incredibly excited by both our evolving data and physician interest in our work in this area. In June, we presented new preclinical data at the European Hematology Association Hybrid Congress. These data demonstrated the strong mechanistic rationale of XPO1 inhibition in myelofibrosis and its ability to target both the JAK and non-JAK pathways.

In light of our data that shows that XPO1 inhibits both JAK and non-JAK pathways, we believe that SELINEXOR can be leveraged both in combination and as a monotherapy. We presented data from our Phase I trial in myelofibrosis last year, as seen on Slide 10. SELINEXOR 60 milligrams was evaluated in combination with ruxolitinib in JAK inhibitor naive patients. Of the 14 patients who received the 60-milligram dose of SELINEXOR, 79% and 58% achieved a SVR35 and TSS50 at week 24, respectively.

Absolute TSS demonstrated very meaningful improvements with an average reduction of 18.5 points at week 24 in the efficacy evaluable population. Diving deeper into the important aspect of durability on Slide 11. As of the data cutoff, there was 100% probability of continuing responses in both the SVR35 and TSS50 over a median duration of follow-up of 32 weeks and 51 weeks, respectively, when SELINEXOR 60 milligrams was used in combination with ruxolitinib indicating that the responses are maintained well beyond 24 weeks. These findings support the potential of the combination of SELINEXOR plus ruxolitinib to offer greater symptom improvement than ruxolitinib alone as our ongoing Phase III study may demonstrate.

Moving to Slide 12, we outlined the trial design for our Phase III SENTRY trial, evaluating the combination of SELINEXOR 60 milligrams with ruxolitinib compared to ruxolitinib alone in 306 JAK-naive myelofibrosis patients. We are encouraged by the strong enrollment into our Phase III clinical trial, given by the positive feedback that we are hearing from clinical trial investigators regarding SELINEXOR’s unique mechanism and clinical profile. Our momentum is also fueled by minimal competitive clinical activity and paucity of effective therapies. Our guidance for reporting top line results remains firmly on track for the second half of 2025.

Turning our attention to endometrial cancer on Slide 14. One of SELINEXOR’s primary mechanisms is to suppress the export of P53 from the nucleus to the cytoplasm. The accumulation of p53 in the nucleus leads to impaired DNA repair, cell-cycle arrest and ultimately increased apoptosis. Clinically, this mechanism is what drives antitumor activity in tumors dependent upon p53, including endometrial cancer.

Advanced in recurrent endometrial cancer is the most common form of gynecologic cancer in the United States with approximately 16,000 patients diagnosed each year. We believe SELINEXOR could play an important role for greater than half of these patients as the first novel oral maintenance therapy for patients with TP53 wild-type tumors. As seen on Slide 15, TP53 wild-type status has an emerging role in the evolving landscape of advanced and recurrent endometrial cancer. Checkpoint inhibitors were recently improved by the FDA in combination with chemotherapy, followed by checkpoint inhibitor maintenance for advanced recurrent endometrial cancer patients regardless of MMR status.

However, the efficacy observed in patients whose tumors are pMMR is markedly less than in the dMMR consistent with the mechanistic rationale for checkpoint inhibitor effectiveness in dMMR solid tumors. These checkpoint inhibitors have been included in combination with chemotherapy, followed by checkpoint inhibitor maintenance in the NCCN guidelines for all patients regardless of MMR status since March of 2023. Patients whose tumors are both pMMR and p53 wild-type represent roughly 50% of all advanced or recurrent endometrial cancer patients. Turning to Slide 16.

At ASCO, we presented very encouraging long-term follow-up data from the exploratory analysis of SIENDO, which evaluated SELINEXOR and maintenance therapy. Patients with p53 wild-type TMMR tumors experienced a median PFS of 39.5 months with SELINEXOR compared to 4.9 months with placebo, resulting in a hazard ratio of 0.36. Acknowledging the limitations in cross-trial comparisons, the median PFS improvement achieved with SELINEXOR in the subgroup exceeds the median overall survival achieved by checkpoint inhibitors in pMMR patients, underscoring the meaningful efficacy achieved with SELINEXOR in these patients. In all patients with p53 wild-type tumors, SELINEXOR demonstrated promising benefit with a median PFS of 28.4 months compared to 5.2 months for placebo, resulting in a hazard ratio of 0.44.

These robust exploratory subgroup data from SIENDO continued to demonstrate the potential of SELINEXOR to provide substantial benefit in a unique and sizable population. In a survey of U.S. physicians who were provided long-term follow-up data achieved with SELINEXOR in patients with — whose tumors are p53 wild type from the SIENDO study, as well as efficacy with the checkpoint inhibitors, 75% indicated future intent to prescribe SELINEXOR as a maintenance therapy for p53 wild-type pMMR endometrial cancer patients. Overall, we believe that SELINEXOR were to be approved in this indication, a majority of patients could benefit from this treatment option.

Let’s also review the updated safety data on endometrial cancer from the SIENDO trial that we presented at ASCO, as shown on Slide 17. Adverse events were generally manageable and well tolerated. The most common AEs observed with SELINEXOR, regardless of grade, were nausea of vomiting and diarrhea. It is important to note that dual antiemetics were not required in this trial.

Grade 3-plus treatment emergent adverse events were rare with the most common events being neutropenia, thrombocytopenia and nausea. Finally, on Slide 18, and as Richard mentioned, we are shifting our expected time line for the top line data readout for our pivotal export EC-042 Phase III trial to early ’26. Based on recent observations and increasing interval between biopsy evaluation and chemotherapy completion has led to a higher-than-expected screen failure rate. Availability of new therapies is also impacting our enrollment, albeit to a lesser degree.

Based upon these observations, we are enhancing our investments by adding additional sites to increase the total number of patients that will need to be screened for this trial. Overall, I continue to be extremely enthusiastic about the potential for SELINEXOR to provide clinically meaningful outcomes in the maintenance setting for patients with p53 wild-type endometrial cancer, especially those with pMMR tumors, where our exploratory subgroup data has demonstrated a median PFS of nearly 40 months, which again exceeds the median overall survival observed with checkpoint inhibitors in patients with pMMR tumors. Lastly, turning to multiple myeloma on Slide 20. We are very encouraged with the results from our STOMP and MM-028 trials that evaluated SELINEXOR 40 milligrams in combination with pomalidomide, and dexamethasone.

The promising data published in the Frontiers of Oncology journal in May of this year underscores SELINEXOR’s potential to expand its position in the multiple myeloma landscape. Selinexor 40 milligrams demonstrated an updated median PFS of 18.4 months and a very tolerable safety profile. Nausea rates were observed in only 32% of patients in the 40-milligram arm, a meaningful improvement relative to the 50% that was observed with SELINEXOR 100 milligram in the BOSTON trial. Our ongoing Phase III trial has the potential to build upon and improve the already favorable data, given that the STOMP and MM-028 cohorts did not require dual antiemetics.

Our Phase III EMN29-SPD trial in multiple myeloma is outlined on Slide 21. This trial is designed to address the unmet need present in patients with multiple myeloma with an all-oral triplet treatment option that can be beneficial to pre- and post-T-cell engaging therapies. We will be working with the European myeloma network, the sponsor of the study, to leverage the positively evolving PFS data observed with SPD-40 and amend the statistical analysis plan to enable a meaningful interpretation of the efficacy and safety of SPD versus EPD. Importantly, we are also seeing a slowdown in enrollment rates due to an increasingly global competitive trial environment with an increased number of Phase III studies targeting the same sites in a similar patient population.

In fact, as of today, four large Phase III trials have already been initiated in 2024, the same number of trials initiated in all of 2023. We now plan to enroll approximately half of the planned sample size and pending the strength of the data, we will engage with regulatory agencies accordingly. Based upon these revised plans, we continue to anticipate top line results in the first half of 2025. In conclusion, our rapidly advancing pipeline presents near-term late-stage opportunities backed by increasingly compelling data.

SELINEXOR has the potential to benefit multiple cancer patient populations with high unmet needs in the near future, enhancing our existing approved indications in multiple myeloma. I will now turn the call to Sohanya for a review of our commercial highlights.

Sohanya Cheng — Senior Vice President of Sales and Commercial Operations

Thank you, Reshma, and good morning, everyone. On Slide 23, I will discuss our commercial highlights for the second quarter of 2024. In the second quarter, XPOVIO net product revenue was $28 million, up 8% compared to our results in the first quarter. Consecutive quarter-over-quarter growth was driven by growth in both new patient starts and refills as XPOVIO is increasingly utilized in a flexible position across the treatment paradigm as a convenient oral regimen with a differentiated mechanism of action.

The results and momentum from the first half of this year and continued strong execution have led us to raise the low end of our net product revenue guidance by $5 million to a new range of $105 million to $120 million. New patient mix remained stable in the second to fourth treatment lines with earlier line use primarily coming from the community setting, which contributed to approximately 60% of XPOVIO net revenues in the second quarter. Demand in the community setting grew more than 10% from the first quarter. Demand in the academic setting remained consistent with the first quarter, with XPOVIO being increasingly used immediately before or after T cell therapies as a way to potentially preserve T cell fitness.

In academic institutions using XPOVIO as a bridging regimen prior to T-cell therapy use, we see shorter duration of therapy of XPOVIO, but this was offset by the increase in new starts in this setting. Overall, in a highly competitive marketplace, we are very pleased with the results that our commercial organization has delivered in the first half of the year with consecutive quarter-over-quarter growth. Now, I’d like to turn to Slide 24 and shift our focus toward milestones accomplished outside of the U.S. I’m pleased with our momentum as we expand our global footprint with continued regulatory and reimbursement approvals of SELINEXOR across the world.

In the second quarter, following the positive recommendation from NICE, expanded reimbursement was achieved in the U.K., as well as South Korea. Additionally, XPOVIO continued to expand its global footprint with additional regulatory approvals in China and other international markets. In summary, Karyopharm’s multiple myeloma franchise continues to impact an increasingly number of patients globally while remaining a profitable business and serving as a critical driver in funding our pipeline. A dedicated commercialization team and partners have the capability for rapid launches in potential future indications as well.

Now, I’d like to turn the call over to Mike to give an update on our financials.

Mike Mason — Chief Financial Officer

Good morning, everyone, and thank you, Sohanya. Turning to our financials since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which are on Slide 26. And Total revenue for the second quarter of 2024 was $42.8 million, reflecting strong momentum compared to $37.6 million for the second quarter of 2023. Net U.S.

XPOVIO revenue for the second quarter of 2024 was $28 million compared to $28.5 million for the second quarter of 2023. The gross to net discount for XPOVIO in the second quarter of 2024 was 29% as compared to 22% in the second quarter of 2023. This was driven by increased 340B utilization, Medicare rebates and expired product returns. We continue to expect 25% to 30% GTN for the full year 2024.

Our total expenses for the second quarter of 2024 were up slightly year over year by 6%, driven by our investments in our late-stage clinical pipeline with three ongoing Phase III trials. R&D expenses for the second quarter of 2024 were $38.4 million compared to $31.5 million for the second quarter of 2023. The increase in R&D expenses is primarily attributable to higher clinical trial costs related to our pivotal Phase III programs. SG&A expenses for the second quarter of 2024 were $31 million compared to $34.5 million for the second quarter of 2023.

The decrease in SG&A expenses was primarily due to ongoing cost reduction initiatives and lower headcount, partially offset by approximately $1 million in debt financing-related expenses. We reported net income of $23.8 million for the second quarter of 2024 compared to a net loss of $32.6 million for the second quarter of 2023. Mostly due to a onetime noncash net gain of $44.7 million on the extinguishment of debt and $14.3 million in gains that were recognized in connection with the refinancing transactions that we concluded in May, which you can see in detail on the related slide in the appendix. As a reminder, these transactions extended the vast majority of our maturities into ’28 and ’29, well beyond our expected data readouts from our three Phase III trials and potential launches.

Cash, cash equivalents, restricted cash and investments as of June 30, 2024, totaled $152.5 million compared to $192.4 million as of December 31, 2023. Based on our current operating plans, we are raising the lower end of our guidance for both total revenue and XPOVIO net product revenue by $5 million and lowering and tightening our overall range of expense guidance by $10 million to $15 million. The operating expense reductions for the remainder of 2024 include lower expected expenses for EMN 29 trial with the planned resizing, as well as continued discipline in our operating costs, including headcount. Specifically, since the beginning of last year, we have reduced our budget headcount by approximately 30%.

Our updated guidance ranges for the full year of 2024 are as follows: Total revenue expected to be in the range of $145 million to $160 million as compared to previous guidance of $140 million to $160 million. XPOVIO net U.S. product revenue is expected to be in the range of $105 million to $120 million as compared to the previous guidance of $100 million to $120 million. We are also lowering our expense guidance for the full year of 2024 as follows: R&D and SG&A expense is expected to be in the range of $250 million to $265 million, which includes approximately $20 million of estimated noncash stock-based compensation expense as compared to previous guidance of $260 million to $280 million.

And finally, we expect our existing cash, cash equivalents and investments, as well as the revenue we expect to generate from XPOVIO net product sales and other license revenues will be sufficient to fund our planned operations into Q1 2026. Note that our cash runway does not include paying up the remaining 2025 convertible notes and our $25 million minimum liquidity covenant under the new term loan. We expect our 2025 operating expenses to be lower than 2024 as we recognize the full year benefits of our ongoing cost-saving initiatives. In summary, we are focused on the advancement of our three Phase III trials and driving commercial performance while continuing to be very diligent when allocating our resources.

I’ll now flip to Slide 27 and turn the call over to Richard for some final thoughts. Richard?

Richard Paulson — Chief Executive Officer

Thank you, Mike. As you can see on Slide 28, we have several meaningful milestones ahead of us in the near future. We believe our continued focus on disciplined capital allocation and expense management provides us with cash runway to achieve these milestones. We are enthusiastic about our innovation and growth strategy, which provides us valuable optionality with our Phase III clinical trials in myelofibrosis, endometrial cancer and multi myeloma.

These trials have the potential to bring transformative benefits to patients and drive substantial progress for our company. As a company, we will continue to strive toward unlocking SELINEXOR’s full potential as we execute in a disciplined manner and deliver on our next phase of growth. Thank you again for joining us today, and I would now like to ask the operator to open the call up to the Q&A portion of today’s call. Operator?

Questions & Answers:

Operator

Thank you. [Operator instructions] One moment please for your first question. Our first question is from Peter Lawson from Barclays.

Unknown speaker — Barclays — Analyst

Hey, good morning. This is Alex on for Peter. Thank you for taking our questions. I just wanted to — I was wondering if you could expand a little bit on what is driving the change in time lines for the endometrial trial and the higher screen failure rates? And beyond adding additional sites, are there any other changes being implemented in the trial here?

Richard Paulson — Chief Executive Officer

Yes. Thanks, Alex. I’ll turn to Reshma for that and really, I think she highlighted it at a high level, but to go into some more detail when we look at kind of the learnings we have in the endometrial trial and what’s happening and how we’re addressing it. So I’ll turn that to Reshma.

Reshma Rangwala — Chief Medical Officer and Head of Research

Yes. Thank you. So I want to start off in the endometrial space, just highlighting the data that we have observed with SELINEXOR in this unique population defined by their p53 status. We first presented long-term data back in July of 2023.

This was part of the ASCO plenary series. It was really important to note, especially from one of the moderators who describe the data is truly unprecedented. And it underscores the benefit that SELINEXOR can achieve in this patient population defined by p53 status. Those data have only gotten stronger.

In fact, at ASCO, SELINEXOR in this population — In those patients who are defined by both p53 wild-type and pMMR status, their data now show an unprecedented 40-month median PFS. That 40 months actually exceeds the overall survival observed with the checkpoint inhibitors in that pMMR patient population — you are correct. We are seeing challenges in our enrollment. One of the main drivers, and it’s a recent observation is this increase in screen failure rate, and it’s very unique to a biomarker it’s a driven trial.

I say that because many of the physicians are submitting their biopsies relatively early during the chemotherapy process. That biopsy is evaluated by physicians for that p53 status. With that said, even if that biopsy is evaluated as p53 wild-type, those patients need to complete months of chemotherapy. And during that time, we have been seeing that they can screen fail for a myriad of reasons, whether it’s for lab reasons, scan reasons, they may need to have surgeries, they may decide that they don’t ultimately want to participate in a clinical trial.

Those reasons contribute to that higher screen fail rate. And as such, we are actively looking at multiple initiatives, increase the total pool of patients that we can screen the major initiative is going to be activating new sites in our current existing countries and potentially in new additional countries. Other initiatives that we are looking at is, of course, doubling down on our medical affairs support looking at outside vendors, we continue to partner very closely with the GOG and ENGOT. Ultimately, we are committed to completing enrollment of this trial and updating everybody on top line results in early 2026.

Unknown speaker — Barclays — Analyst

Great. That’s helpful. Thank you very much.

Richard Paulson — Chief Executive Officer

Thanks, Alex.

Operator

The next question will be coming from Maurice Raycroft from Jefferies.

Maury Raycroft — Analyst

Hi. Thanks for taking my questions. Maybe just a quick follow-up to the last one. Are you saying anything more about how many new sites you anticipate opening and what regions you plan on opening those sites in?

Reshma Rangwala — Chief Medical Officer and Head of Research

Yes. Thanks for the question, Maury. No, we’re not providing any additional color on those details just primarily looking at opening up some new sites in our existing countries and like I said, potentially additional countries and then continuing to support the many sites that have already been activated in our current trial. So I think those main focus really will enable that increased screening pool that we need to achieve to enable those top line results in the first — in early 2026.

Maury Raycroft — Analyst

Got it. And is there any way to potentially help mitigate the issue with the biopsy process? I guess, can Karyopharm do anything to help on that front? And then, could part of the outcome of this lead to an enrichment of the p53 wild-type pMMR population? Or how are you thinking about that?

Reshma Rangwala — Chief Medical Officer and Head of Research

So I will say the biopsy process is already going very smoothly. In endometrial cancer, molecular classification is really becoming the standard of care, both because physicians are evaluating the MMR status. — as well as other biomarker classifications, including p53, Poli, etc. So physicians are really used to evaluating biopsies in the case of our clinical trial.

They just submit that biopsy to Foundation Medicine. They process it very quickly, and the results are turned around within a matter of days. The main driver specific to our trial is again that interval between when the biopsy is submitted in the months of chemotherapy that they still need to complete. And that, unfortunately, is nothing — there’s nothing that we can do to offset that process.

In terms of your second question, it’s a good one. And I think like naturally, we are going to see patients who are pMMR, as well as p53 wild type based upon local testing disproportionately submitting tumors to SMI. So I think we will see that rate rise over time.

Maury Raycroft — Analyst

OK. Thanks for taking my questions. I’ll hop back in the queue.

Richard Paulson — Chief Executive Officer

Thanks, Maurice.

Operator

Next question will be coming from Colleen Kusy from Baird.

Colleen Kusy — Analyst

Hi. Good morning. Thanks for taking our questions. Among those enrolled another question on the endometrial study.

Can you comment on any sort of PFS metrics so far and how that’s tracking versus your expectation? And whether kind of enrolling some of these pMMR p53-wild-type patients might be pushing out the data as well, just given how long — how strong the CNO data has been?

Reshma Rangwala — Chief Medical Officer and Head of Research

Yes. Thanks for the question, Colleen. So no, we do not have any insight in terms of the results from this trial. It’s a double-blinded trial.

We also are very much blinded to the results across either one of these arms. So no insight there. I think I’ll just go back to the SIENDO data in that p53 wild-type subgroup that we’ve had an opportunity to report on multiple times. That data just continues to get stronger, right? In that large p53 wild-type subgroup, we are now seeing a median PFS of 28.4 months.

And I’ll reiterate in that p53 wild-type TMMR subgroup, those data now demonstrated a median PFS of 40 months, truly unprecedented data and really underscores the strength of the benefit that can be achieved with SELINEXOR we’ve incorporated those PSS into our assumptions. So we assume a very meaningful PFS benefit at the time of the top line results and again, has already been incorporated into the projections that inform that early 2026 top line result readout.

Colleen Kusy — Analyst

Got it. That’s helpful. And then, on the screen failure rate, can you comment if the TP53 wild-type biomarker is roughly as prevalent as you thought it was so far in the screening process? Is it still roughly around 50%?

Reshma Rangwala — Chief Medical Officer and Head of Research

Yes, it is. It is sitting nicely in that assumed rate of more than half of all patients.

Colleen Kusy — Analyst

Great. And then, one commercial question, if I can. Sohanya, can you just give us a sense of the duration of treatment for the pre- and post T cell therapies you’re seeing in the academic centers? Is it like a one month or maybe low single digits, but just kind of help us get a range on that, please?

Sohanya Cheng — Senior Vice President of Sales and Commercial Operations

Yes. Thanks, Colleen. So we don’t disclose exact months of duration because we have to triangulate multiple data sources, it takes time for that to mature. However, take a step back and look at trends overall, obviously, we see a long-term trend since the launch of the drug in terms of increasing duration.

The recent dynamics in the competitive landscape, obviously, with bridging and post T cell therapies have obviously impacted duration, but this is a smaller proportion of our patients. The large majority of our patients remain in the early align, second, third and fourth line — and really, that helped to propel our duration up.

Colleen Kusy — Analyst

Great. Thanks for taking our questions.

Richard Paulson — Chief Executive Officer

Thanks, Colleen.

Operator

Next on the line is coming from Brian Abrahams from RBC.

Brian Abrahams — Analyst

Hi. Good morning. Thanks for taking my questions. Maybe shifting gears to myelofibrosis.

The Phase III 034 study is based on some of the data you presented on Slide 10, where you showed quite robust benefits for SELINEXOR on top of rux, but in a relatively small number of patients. So I guess I’m curious, as the trial is continuing, if there may be any opportunities to adjust the powering or design of the study based on the ongoing data or on regulatory outcomes from Pelabresib the late-stage drug that’s also in development. And then, maybe secondarily, on MF, it looked like the SELINEXOR monotherapy study was — time line was pushed out just a bit there. Just wondering if you could tell us kind of how that study is going and the extent of the data we should be looking for now in the back — at the end of this year or early next?

Reshma Rangwala — Chief Medical Officer and Head of Research

Thanks for the question. So we’re — we remain really confident about myelofibrosis. I think as you mentioned, the strength of the data are unparalleled. And the reason I say that is because, yes, although we have a smaller cohort of patients in which we evaluated the efficacy with SELINEXOR plus ruxolitinib, specifically a 79% SVR35 rate and a 58% TSS50 rate at week 24, it only builds upon the data that we have evaluated with not only SELINEXOR but the combination, I underscore the preclinical data, the mechanistic data that really suggests that SELINEXOR in XPO1 inhibition is targeting both JAK and non-JAK pathways, as well as the totality of the data that really suggests that when SELINEXOR is combined with ruxolitinib, you can see additive, if not synergistic effects.

Layer on now the clinical data that have demonstrated monotherapy activity. This goes back to the essential trial in that relapsed/refractory JAK — previously exposed JAK population. And now, of course, you have the Phase I data specifically evaluating SELINEXOR in combination with ruxolitinib. So when I evaluate our opportunity and the strength of the data, it’s really looking at all of those data sets that really inform the potential of SELINEXOR in myelofibrosis.

What we also know from both patients, as well as physicians is that the efficacy has to extend beyond just those SVR35 and TSS50 rates. I add that because we’re also seeing very impressive durability. At the time of the most recent data cutoff, none of the patients had actually progressed either from an SVR35 standpoint or TSS50. So what we are seeing is remarkable SVR35 and TSS50 rates, as well as the corresponding durability that extend well beyond that week 24 time point.

Lastly, I’ll mention in terms of 044, Yes, we did push out the time lines a little bit. Now, we are looking at end of ’24, beginning of ’25. It’s a smaller patient population. So these are still JAK-naive patients.

However, their platelet count needs to be within that 50 to 100. So it is a smaller population as compared to that patient population enrolling in the Phase III. Still lots of enthusiasm, and we look forward to providing data from that study shortly.

Brian Abrahams — Analyst

That’s really helpful. I guess I was thinking if the effect size in the Phase III was maybe even more robust than what you had seen in the Phase II, if there might be an opportunity to maintain powering, but cut the trial size down a bit and accelerate time lines there?

Reshma Rangwala — Chief Medical Officer and Head of Research

Yes. It’s a good question. I mean, we are completely blinded to the results, so that’s not something that we can do. But like all of our Phase IIIs, we do have an independent DMC that is evaluating the results.

And based upon their assessment, we’ll certainly consider if that opportunity exists for the trial.

Brian Abrahams — Analyst

Thanks.

Richard Paulson — Chief Executive Officer

Thanks, Brian.

Operator

[Operator instructions] Last question on the line will be coming from Jonathan Chang from Leerink Partners.

Matt Cowper — Analyst

Great. Hi, guys. This is Matt on for Jonathan. Thanks for taking my question.

Just looking at some of the details of the cash runway, including the liquidity covenant, etc., how confident are you that you have sufficient cash from a way to get to the updated endometrial cancer top line readout? And how should we be thinking about the monetization of assets such as KPT-9274 as it relates to making the time line work? And lastly, can you comment if there are other programs in the pipeline with similar potential for out-licensing such as 9274.

Richard Paulson — Chief Executive Officer

Yes. Thanks for the question. I’ll let Mike talk to the first part, and then I can jump into the second and third question.

Mike Mason — Chief Financial Officer

Sure. So a reminder, our previous cash runway was into the end of 2025. We’ve tightened our 2024 opex guidance to be $250 million to $265 million, which includes $20 million of stock comp, which is down from $260 million to $280 million previously. And part of that lowering expenses was the plan resizing with our EM 29 trial and just a continued discipline on operating costs.

Because yes, we realized the importance of extending that cash runway. We have three pivotal readouts. First one is myeloma, which is in the first half of 2025. Second one is myelofibrosis in the second half of 2025 and the third in endometrial in early 2026.

So putting all those together, our cash runway gets us into the early 2026, excluding the convert that we have due in October 2025.

Richard Paulson — Chief Executive Officer

Yes. And I think if we build on, as you mentioned, talking about KPT-9274, it’s a novel first-in-class oral small molecule dual inhibitor of PAK4 and MPG that was discovered by Karyopharm and is part of our early stage programs. So obviously, recently, as we announced today, we were able to receive both rare pediatric disease designation and orphan drug disease designation. So I think a really strong opportunity where we’re going to be looking to partner or out-license that asset to make sure that we can recognize the full value of it and help to work to bring it to patients or enable someone else to work to bring to patients.

So that’s a strong opportunity for us, obviously, with some strong value behind it, given those designations and given the high unmet need in both rhabdosarcoma and Ewing sarcoma. Also, I think as we talked to before, we have ELTANEXOR, which is our second novel sign compound, which we will look at potential partnerships in terms of that asset across the globe. Right now, it’s currently partnered just in Asia Pac. So that gives us optionality to look at moving forward.

And then, yes, we have a couple of other assets within the pipeline that we’re always opportunistic to see what’s the best way to recognize value from those assets. So I think some good optionality in terms of our BD area and obviously with KPT-9274 and the recognition and the areas we’ve just been recognized by the FDA, I think that adds significant value and looking to recognize that value.

Matt Cowper — Analyst

Got it. Thank you so much.

Richard Paulson — Chief Executive Officer

Thanks.

Operator

There are no further questions at this time. I’d now like to turn the call back over to Mr. Richard Paulson for final closing comments.

Richard Paulson — Chief Executive Officer

Thank you, operator, and thank you, everyone, for joining us on today’s call. We are focused on accelerating the momentum as we look to deliver on our next phase of growth, and our people continue to strive each day for patients with high unmet needs as we work to generate value for patients and shareholders. We thank you for joining again, and have a great day, everyone.

Operator

[Operator signoff]

Duration: 0 minutes

Call participants:

Elhan Webb — Senior Vice President, Investor Relations

Richard Paulson — Chief Executive Officer

Reshma Rangwala — Chief Medical Officer and Head of Research

Sohanya Cheng — Senior Vice President of Sales and Commercial Operations

Mike Mason — Chief Financial Officer

Unknown speaker — Barclays — Analyst

Maury Raycroft — Analyst

Maurice Raycroft — Analyst

Colleen Kusy — Analyst

Brian Abrahams — Analyst

Matt Cowper — Analyst

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