Q1 2025 Karyopharm Therapeutics Inc Earnings Call
Chloe: Good afternoon, my name is Chloe and I will be your conference operator today. At this time, I would like to welcome everyone to the Krio Forum of Therapeutics' first quarter 2025 financial results conference call. There will be a question in answer session to follow. Please be advised that this call is being recorded at the company's request. Please be advised that this call is being recorded at the company's request.
Speaker Change: Thank you Kelly and thank you all for joining us on today's conference call to discuss Cariole farms first quarter 2025 financial results and recent company progress.
Speaker Change: We issued a press release after the market closed detailing our financial results for the first quarter of 2025.
This release, along with a slide presentation that we will reference during today are available on our website.
Lori: For today's call as seen on slide two I'm joined by Richard Regiment, So Hong you and Lori will provide an update on our results for the first quarter of 2025 and review new data that we're showing for the first time today in myelofibrosis.
Lori: Before we begin our formal comments I'll remind you that various remarks, we will make today constitute forward looking statements for purposes of the safe Harbor provisions under the private Securities Litigation Reform Act with 1995 as outlined on slide three.
Lori: Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section of our most recent Form 10-Q and 10-K on file with the SEC.
Lori: And in other filings that we may make with the SEC in the future.
Lori: Any forward looking statements represent our views as of today only.
Lori: While we may elect to update these forward looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change.
Lori: Therefore, you should not rely on these forward looking statements as representing our views as of any later date.
Richard Regiment: I'll now turn the call over to Richard Please turn to slide four.
Speaker Change: Thank you Brandon and thank you all for joining us today for carrier farms Q1, 2025 earnings call.
Speaker Change: As we continue to execute on our innovation and growth strategy. We are pleased that our phase III trial in patients with JAK naive myelofibrosis as past its prespecified futility analysis and continues as planned without modifications.
Speaker Change: We are very focused on completing enrollment in this trial, while also advancing enrollment in our phase III trial in endometrial cancer as outlined on slide five.
Speaker Change: As we have discussed in the past we have a profitable commercial organization in multiple myeloma that can be leveraged to drive rapid commercialization, if we receive approval in additional disease areas.
Speaker Change: Turning to slide six.
Speaker Change: We are excited to share with you today, new clinical data, which further strengthens our conviction and selinexor is potential in combination with rux or at nib in JAK naive myelofibrosis patients.
Speaker Change: The data that Rachel will take you through his selinexor monotherapy data.
Rachel: Heavily pretreated hard to treat population from a randomized phase II export M F. Both three five trial.
Rachel: The data are very encouraging because they continue to show Selinexor may have an impact across each of the four key hallmarks of the disease.
Rachel: When combined with other clinical and preclinical data we have shared previously this tells a consistent story, which supports our belief that the combination of Selinexor plus rux they wouldn't have.
Rachel: Has the potential to meaningfully improve patient outcomes and redefine the standard of care in myelofibrosis.
Rachel: We look forward to sharing data with you from our phase III <unk> trial, which is evaluating selinexor in combination with rux, so letting them towards the end of this year or in early 2026.
Rachel: We have now enrolled approximately 80% of the 350 patients that we're targeting for this study and expect to complete our targeted enrollment in the June July timeframe.
Rachel: As we think about our potential in myelofibrosis. It is worth remembering how we got here, which is outlined on slide seven.
Rachel: We've been taking deliberate steps over many years to put us in the position we are in today.
Rachel: We continue to progress our phase III century trial faster than historical benchmarks, while remaining incredibly focused on high quality clinical trial execution.
Rachel: As outlined on slide eight leading key opinion leaders in myelofibrosis, including Dr ramp Ho from Memorial Sloan Kettering.
Rachel: And Doctor masquerading as from Mount Sinai continue to highlight the need for new treatment options for patients with myelofibrosis and are encouraged by the strength of our phase one combination data.
Rachel: Finally, we continue to believe that the commercial opportunity in myelofibrosis is transformational.
Rachel: On slide nine if approved we believe the peak revenue for potential for Selinexor in myelofibrosis is up to approximately $1 billion in the U S alone.
Rachel: Based on our market research, including discussions with leading key opinion leaders on our phase one data and the fact that we are looking to combine selinexor with the existing standard of care, we believe that commercial uptake would be rapid we.
Speaker Change: We are eager to see the outcome of our phase III trial and the potential opportunity ahead, now I'd like to turn the call over duration.
Speaker Change: Thank you Richard before I get into the new data, let's quickly with you why we believe selinexor as an X P. O. One inhibitor is a rational mechanism to evaluate <unk> in patients with myelofibrosis, starting on slide 11.
Speaker Change: Hello next what prevents the nuclear export of various proteins and messenger RNA molecules inhibiting both Jack and non JAK pathways. The ladder, which includes the nuclear localization and activation of piece of <unk> three an important tumor suppressor in myelofibrosis, given that approximately 95% of myelofibrosis.
Speaker Change: Patients are P 63 wild type.
Speaker Change: Let's start by reviewing the unmet need in JAK naive myelofibrosis on slide 12, Selinexor has the potential to help patients with myelofibrosis and our opportunity to redefine the standard of care as the first combination therapy.
Speaker Change: To set the stage there hasn't been a lack of new treatment options given that the JAK inhibitors are the only approved class of therapies Brookfield.
Speaker Change: <unk> has been the standard of care for over 13 years as the potential first combination therapy in myelofibrosis, Selinexor plus Brooks to letting it would be a convenient oral therapy.
Speaker Change: Hello fibrosis community has clearly indicated interest in adopting given the rapid deep and durable spleen reduction symptom improvement observed from the phase one study.
Speaker Change: Let's now focus on the four key hallmarks in myelofibrosis.
Speaker Change: First let's look at spleen volume reduction I think it's a helpful reminder, that only approximately one third of patients achieved the spleen volume reduction of greater than 35% with Brookfield at Nib alone.
Speaker Change: As we have shared before our phase one data show that selinexor, plus rux or letting it more than doubles that SVR 35 rate.
Speaker Change: And as symptom improvement as a reminder, data from our phase one trial of Selinexor in combination with rux letting it showed an average 18.5 point improvement in absolute PSS at week, 24, which suggests a meaningful improvement over the 11 to 14 point improvement achieved by <unk>.
Speaker Change: <unk> and <unk> as observed in the phase III manifest two and transform one trials.
Speaker Change: Third is hemoglobin stabilization and transfusion burden the new data, we will be reviewing today shows higher hemoglobin levels, lower transfusion burden and much lower rates of all grade and grade three plus anemia in patients randomized to selinexor compared to physicians choice, primarily JAK inhibitors, including <unk>.
Speaker Change: <unk>.
Speaker Change: Fourth is disease modification there is minimal evidence of disease modification with JAK inhibitors. The new monotherapy data showed a substantial reduction in key cytokines that are critical to myelofibrosis pathogenesis timken development and anemia.
Speaker Change: We believe this data likely indicates that selinexor is having an impact on the underlying disease, which enables both monotherapy as well as additive if not potentially synergistic benefit when combined with other therapies, including <unk>.
Speaker Change: Turning to slide 13, our export M. S. 035 trial is a randomized phase two trial that is evaluating selinexor monotherapy versus physicians choice. The study was designed to evaluate the efficacy and safety of Selinexor in a more heavily pretreated myelofibrosis population.
Speaker Change: Importantly, this trial allows for patients to crossover from physicians choice to Selinexor, if their screen that predefined progression criteria to be eligible for the trial patients who needed at least six months of prior exposure to a JAK inhibitor.
Speaker Change: This trial was originally designed to randomize 112 patients. However, we stopped enrollment in 2023 to focus our resources on our ongoing phase with century trial.
Speaker Change: Slide 14 contains the baseline characteristics for the 24 patients that we enrolled in the trial.
Speaker Change: In mind that this trial enrolled a very different patient population than the patients we are enrolling in our phase III century trial.
Speaker Change: Patients in this trial were heavily pretreated with an average of two prior lines of therapy with some patients having up to four lines of prior therapy. This is also a very frail high risk population I would direct your attention to the fact that 17% of patients are triple negative and 21% or high risk.
Speaker Change: Furthermore, these patients are generally cytopenia with hemoglobin levels between nine and 10 five of these patients were transfusion dependent prior to enrolling in the trial slide.
Speaker Change: Slide 15 contains the spleen volume reduction observed in this trial, we evaluated the maximum SVR experienced at any time in the efficacy evaluable populations. The eight patients shown in blue were treated with physician's choice. The patients represented by the solid green bars in the middle of the slide were randomized to sell them.
Speaker Change: Next are the additional five patients in the textured green bars on the far right where patients that progressed on physician's choice and crossed over to Selinexor.
Speaker Change: Is this clear on this slide spleen volume reduction was greater in those patients that received selinexor at any time compared to the group that received physician's choice.
Speaker Change: Fact, all but one patient in the Selinexor arm achieved some degree of spleen volume reduction, whereas only half of the patients and the physicians choice arm experienced a decrease in spleen volume.
Speaker Change: 38% of the Evaluable patients and the physicians choice arm achieved an SVR 25 at any time, we're 67% in the Selinexor arm, including patients that crossed over achieved in SVR 25 for <unk>.
Speaker Change: They are 35 rates were more than double for selinexor, 13% of patients and the physicians choice arm achieved this level of spleen volume reduction or greater compared to 33% in the Selinexor arm.
Speaker Change: Slide 16 contains a very compelling spider line graph that looks at the impact that selinexor has on screen size on patients that crossed over.
Speaker Change: Thus had progressed on prior therapy.
Speaker Change: Six patients who crossed over from physicians choice to Selinexor Fiverr valuable and are shown on the slide four of these five patients received <unk> as a physician's choice prior to crossover. So in fact, despite the line graph really demonstrates selinexor its effect on the spleen size and Russell at Nib refractory.
Speaker Change: Patients.
Speaker Change: The first column that's represented by the Y axis represents the baseline spleen level for each patient.
Speaker Change: Second series of data point represents the maximum reduction of spleen volume physician's choice of Rux I'll, let Ned the third series of data points represent the spleen volume growth experienced at the time of progression. The fourth series of data points than represent spleen volume relative to baseline after the <unk>.
Speaker Change: <unk> crossover to Selinexor into.
Speaker Change: The interpretation of these data are very clear each patient that crossed over to selinexor demonstrated clear and meaningful reductions in their spleen volume after crossing over.
Speaker Change: Indicating that selinexor is targeting pathways beyond the JAK stat pathway, enabling both monotherapy activity as well as additive if not synergistic activity when combined with <unk>.
Speaker Change: Similar to spleen volume reduction, we also see meaningful symptom improvement with Selinexor monotherapy.
As you see on slide 17, there was no improvement in symptoms for the patients randomized to physicians choice in contrast to seven efficacy evaluable patients randomized to Selinexor reported a 5.9 point improvement in absolute TSS at week, 24, and 29% achieved.
TSS 50, if you look at all patients treated with selinexor, including those that crossed over this group reported a three seven point improvement in absolute TSS and 18% achieved a T. S has 50 at week 24.
Speaker Change: Please note that all of these figures exclude the fatigue domain, which is consistent with how we are calculating absolute TSS in our phase III century trial.
Speaker Change: As we have previously discussed we have aligned with FDA on this approach and it is consistent with the comfort and Jakarta trials that led to approvals for rux, I'll, let Ned and the drought net respectively.
Speaker Change: Turning to slide 18, we show how hemoglobin levels changed over time patients randomized to Selinexor are shown in green patients on physician's choice are shown in blue there.
Speaker Change: Actually you can see that hemoglobin levels are substantially higher than the selinexor arm throughout the study duration.
Speaker Change: Let's take this a step further and look at transfusion burden as shown on slide 19, starting with the swimmers plot on the left we use the same colors from the prior slide patients randomized to Selinexor are in green patients randomized to physicians choice are in blue and patients that crossed over to Selinexor or show.
Speaker Change: And the yellow extensions at the end of the Blue lines. The red dots represent transfusions five patients were transfusion dependent at baseline three and the physicians choice arm and two in the Selinexor arm.
Speaker Change: Notably patient for 112 Dash 003 in the Selinexor arm with transfusion dependent prior to randomization.
Speaker Change: Visually you can see right away that patients that start on physician's choice received many more transfusions.
Speaker Change: Why is likely because X P. L. One inhibition is modifying the underlying disease and helping the patients produce more healthy bone marrow, we expect to be able to answer. This question more definitively what the results from the phase III century trial.
Speaker Change: Now we ask ourselves why are we seeing higher hemoglobin levels unless transfusion, let's look at slide 20, which outlines the key cytokines that are relevant in myelofibrosis.
Speaker Change: Starting with myelofibrosis pathogenesis IL six and IL eight are irrelevant to malignant mutated clonal expansion Pat splenomegaly.
Speaker Change: And bone marrow angiogenesis.
Speaker Change: IL six and IL eight also affect constitutional symptoms and drive inflammation as does TNF alpha.
Speaker Change: Anemia is affected by IL, six hepatocyte, and TNF Alpha which plays a role in suppressing normal hematopoietic and also blocks.
Speaker Change: Iron availability.
Speaker Change: Please keep all of this in mind as we review Slide 21, we obtained plasma samples at baseline and again at week four on a subset of the patients that participated in the trial size from the Selinexor arm and five from the physicians choice arm, we plotted the cytokine changes using a standard dendrogram plot.
Speaker Change: And purple Hughes represent a decrease in cytokines red and teach us represent an increase the decreases are what we are looking for as you look at the slide please focus on the box in the middle of the screen. This is where the fourth cytokines that are relevant to myelofibrosis are shown you'll see the arrows pointing to IL <unk>.
Speaker Change: IL eight have decided and TNF alpha.
Speaker Change: For these four key cytokines, we are seeing clear reductions as early as week four and the Selinexor arm, while there are increases in the cytokines and the physicians choice arm in the Blue box at the bottom you can see the actual percentage changes, including a 37% median reduction in IL, 829% median reduction.
Speaker Change: And IL, 625% median reduction in TNF Alpha in a 30% median reduction in upside and for those patients and the Selinexor arm.
Speaker Change: In contrast, three of the four medians increased for the physicians choice arm. These data suggests that selinexor is modifying the underlying disease something that JAK inhibitors have not been able to adequately demonstrate.
Speaker Change: Let's now turn to the safety data on Slide 22, Selinexor continues to demonstrate a manageable safety profile Selinexor are similar to physicians choice for both all grade and grade three plus eight years.
Speaker Change: In particular nausea was only 33% in the Selinexor arm compared to physicians choice similar rates of thrombocytopenia were observed across the two arms. A notable exception is anemia, where both all grade and grade three plus anemia, a meaningfully decreased in the selinexor arm compared to physicians choice.
Speaker Change: Specifically all grade anemia.
Speaker Change: With 25% in the Selinexor arm compared to 58% in the physicians choice arm in grade three plus anemia was 17% in the Selinexor arm compared to 58% in the physicians choice arm. These data are notable given that we are not only seeing higher hemoglobin levels and lower transfusion burdens, which I did.
Speaker Change: Just on the prior slides, but also lower anemia easing or safety data further suggestive of the disease modification lastly, I'll note that none of the patients randomized to selinexor discontinued treatment due to an adverse event.
Speaker Change: Turning to slide 23, we are pleased that our phase III century trials successfully passed its prespecified futility analysis.
Speaker Change: The D. SMB recommended that the study continue as planned without modification following a review of safety and efficacy data in the first 61 patients all of whom were followed for at least 24 weeks. In this study we continue to make strong progress towards our goal of enrolling 350 patients.
Speaker Change: Back to complete enrollment very shortly in the June July timeframe, but the data that I just shared with Selinexor monotherapy in hard to treat heavily pretreated patient population I'm very encouraged with the consistency that is being observed across our multiple clinical and preclinical data sets. These data continue to suggest that the.
Speaker Change: Combination of Selinexor, plus rux, so letting it has the potential to be clinically additive if not synergistic in a JAK naive patient population, that's leading to substantially higher SVR in TSS improvements as compared to each agent alone as observed in our phase one combination study.
Speaker Change: Together with the hemoglobin stabilization and lower transfusion burden as well as the potential for disease modification. The data continue to suggest that selinexor is affecting each of the four key hallmarks of myelofibrosis.
Speaker Change: Look forward to continuing to demonstrate this with the upcoming results from our phase III century trial and building upon Selinexor is a well established safety profile with over 30000 patients treated across multiple indications and the potential for patient convenience with an all oral combination.
Speaker Change: Now, let's shift our focus to endometrial cancer, where P. 53, wild type is such an important biomarker as seen on slide 25 patients with both MMR proficient at T. P 53, wild type tumors make up approximately 50% of all advanced or recurrent endometrial cancer cases, representing a very.
Speaker Change: Sizable group of patients Selinexor, primarily functions by blocking the export of P 53 from the nucleus to the cytoplasm. When P 53 accumulates in the nucleus. It leads to disrupt the DNA repair processes cell cycle arrest and increased a pop ptosis.
Speaker Change: I remain encouraged with the potential of selinexor to achieve clinically meaningful outcomes in the maintenance setting for patients with P 53, wild type endometrial cancer.
Slide 26, we outlined the study design for our ongoing export E. C 042 trial enrollment in the trial is progressing steadily and we continue to expect to report topline data in the middle of 2026.
Speaker Change: Lastly, our phase three and then 29 S. P. D trial as outlined on Slide 28. This trial aims to address the unmet need of patients with multiple myeloma by offering an all oral triplet treatment option that could also benefit those undergoing pre and post T cell engaging therapies.
Speaker Change: We expect to report topline data from this event driven trial in the first half of 2026, I will now turn the call too so hernia.
Speaker Change: Thank you Ray Smith on Slide 30, I will discuss our commercial highlights for Q1 2025, we.
Speaker Change: We delivered 5% demand growth in Q1 year over year, although net product revenue was $21 1 million and was adversely impacted by a 5 million increase in the product return reserves due to atypical returns have expired products, primarily 80 milligrams and 100 milligram exposure units.
Speaker Change: These higher dose units were purchased by clinics and hospitals. Following the 2020 approval of the <unk> hundred milligram triplet combination.
Speaker Change: The majority of exposure that is prescribed today are 40 milligrams and 60 milligram doses and we expect product returns will be similar to historical levels in future quarters.
As we look at the key drivers of demand in Q1, we delivered year over year growth in prescriptions across both academic and community settings of care with the latter contributing to 60% of our sales.
Speaker Change: The multiple myeloma market remains highly competitive and we are expecting additional new entrants this year.
Speaker Change: Within this market exposure is positioned in the community as a flexible therapy with a differentiated mechanism of action oral convenient option following treatment with an anti CD 38 therapy as well as in patients who cannot access or fail a T cell engaging therapy.
Speaker Change: In the academic setting compared to last year, we're seeing increasing use of exposure you know immediately before and following T cell therapies we.
Speaker Change: We expect to continue to display a resilience in a competitive multiple myeloma market and in light of the atypical level of returns in the first quarter. We now expect to be tracking towards the lower end of our guidance range for net product revenue of $115 million to $130 million.
Speaker Change: Moving to slide 31, we continue to expand global patient access to Selinexor, which is translating into growth in royalty revenue from Menno Verine anti gene and other international partners Royal.
Speaker Change: Royalty revenue increased 57% to $1 7 million in the first quarter of 2025 compared to the first quarter of 2024, reflecting increasing global demand for exposure and exposure.
Speaker Change: As we now move to potential new indications our commercial team is preparing for a very rapid launch in myelofibrosis if approved.
Speaker Change: As outlined on slide 32, we continue to believe that our peak annual revenue opportunity in the U S alone is up to approximately 1 billion with additional royalty and milestone revenue globally.
Speaker Change: On slide 33, we outline why we believe we are so well positioned for a rapid launch in myelofibrosis.
Speaker Change: As we have shared previously 75% of the physicians that we surveyed said that they intend to adopt a combination therapy in myelofibrosis, if one becomes available.
Speaker Change: Selinexor is approved in combination with <unk>. So looking at we could be the first combination therapy on the market.
Speaker Change: Would be an all oral therapy, which makes adoption much easier, especially in the community setting.
Speaker Change: At this point there is an 80% overlap in the community between myelofibrosis and multiple myeloma prescribers that our organization is already calling on which enables us to drive a rapid launch and minimize the upfront investment required for the launch.
Speaker Change: Finally in endometrial cancer as shown on slide 34, we continue to believe that we have a significant opportunity in the P. 53, Wild type P. M. M. R patient population, which represents approximately 50% of advanced or recurrent endometrial cancer patients.
Speaker Change: Similar to what I outlined for myelofibrosis, there's a large overlap between the potential community based oncologists carrying for endometrial cancer patients and those that were already engaging with.
Laurie: Now I'll turn the call over to Laurie.
Laurie: Good afternoon, everyone and thank yous behind yet.
Laurie: Turning to our financials since we issued a press release earlier today with the full financial results.
Laurie: Focus on the highlights and reviewing our guidance for 2025 on slide 36.
Laurie: Total revenue for the first quarter of 2025 was $30 million compared to $33 1 million for the first quarter of 2024.
Laurie: U S net product revenue for the first quarter of 2025 was $21 1 million compared to $26 million for the first quarter of 2024.
Laurie: A decrease in net product revenue was due to an increase in the gross to net provision primarily related to the higher dose product returns recorded in the first quarter of 2025.
Laurie: Resulting in a 5 million increase in our product return reserves compared to the first quarter of 2024.
Laurie: Related to this.
Laurie: So net provisions for EXPAREL deal in the first quarter was 45% compared to 29, 3% in the same period in 2024.
Laurie: We expect our gross to net provision will return to historic levels, starting in the second quarter.
Laurie: R&D expenses for the first quarter 2025, with $34 6 million compared to $35 4 million for the first quarter of 2024.
Laurie: The decrease with theater reduction in head count and contractors related to ongoing cost optimization initiatives harsher.
Laurie: Partially offset by increased clinical trial activity related to our pivotal phase III study in myelofibrosis.
Laurie: SG&A expenses for the first quarter of 2025, or 27 4 million compared to $29 5 million for the first quarter of 2024.
Laurie: The decrease was due to a reduction in head count and contractors in connection with cost optimization efforts.
Laurie: We.
Laurie: <unk> to be very diligent in allocating our resources and pipeline prioritization.
Laurie: While striving to deliver additional cost savings in 2025.
Laurie: And continuing to advance our phase III clinical trials and driving our commercial performance.
Laurie: We exited first quarter 2025, with cash cash equivalents restricted cash and investments of $70 3 million compared to $109 1 million as of December 31, 2024.
Laurie: As a reminder, cash burn is typically highest in the first quarter of each year.
Laurie: Based on our current operating plans our guidance for the full year of 2025 is as follows.
Laurie: Total revenue of 140 to 155 million.
Laurie: The Sting of U S net product revenue.
Laurie: And license royalty and milestone revenue expected to be earned from our partners, primarily met Irene and entertain.
Speaker Change: Yes exposure net product revenue to be in the range of $115 million to $130 million.
Speaker Change: As a result of the atypical level returns in the first quarter. We now expect total revenue net product revenue will be towards the lower end of these ranges.
Speaker Change: R&D and SG&A expenses to be in the range of $2 $40 million to $55 million.
Speaker Change: And finally, we expect our existing cash cash equivalents and investments.
Speaker Change: Our revenue, we expect to generate from Mexico to U S net product sales.
Speaker Change: And other license revenue.
Speaker Change: And ongoing disciplined expense management will fund our planned operations into early Q1 2026.
Speaker Change: This guidance does not include payments for the remaining 2025 convertible notes and our $25 million minimum liquidity covenant under our term loan.
Speaker Change: Considering the repayment of the 2025 convertible notes and the minimum liquidity Covenant, we expect cash cash equivalents and investments will fund operations into early Q4 2025.
Speaker Change: In closing we are exploring various opportunities to extend our cash runway and our focus on the advancement of our phase III clinical trial.
Speaker Change: <unk> commercial performance and continuing to be very diligent when allocating our resources.
Richard Regiment: I will now turn the call back to Richard for some final thoughts.
Speaker Change: Yeah.
Speaker Change: Turning to slide 38, as Lori mentioned, we are exploring various opportunities to extend our cash runway as we are focused on delivering the potentially transformational opportunity ahead of us in myelofibrosis.
Speaker Change: Also continuing to advance our phase III trial in endometrial cancer and deliver solid commercial results.
Speaker Change: Fibrosis, and endometrial cancer, depending on the outcome of the data are both game changing opportunities for patients our organization and our shareholders alike.
Speaker Change: We are working hard to unlock our innovation and growth strategy and are very excited by our growing body of data and what it can mean for patients with myelofibrosis. Thank.
Speaker Change: 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.
Speaker Change: <unk>.
Speaker Change: Thank you ladies and gentlemen, we will now begin the question and answer session should you have a question up These press star followed by the one on your telephone keypad, you'll hear it problem that you had has been raised and should you wish to cancel your request. Please press star followed by the two I would like to advice everyone to have a limit of one.
Speaker Change: And one follow up.
Speaker Change: And if you're using a speaker phone please lift the handset before pressing engines one moment. Please for your first question.
Galena Disney: And your first question comes from the line of Galena Disney from Baird. Please go ahead.
Speaker Change: Yeah.
Speaker Change: Hi, good afternoon, thanks for taking our questions and congrats on the continued progress and the new data I think for the for all the updates so unless.
Speaker Change: On the futility analysis can you talk about what that was based on and what the options where could the study had been upsides. If the do you have to be have suggested it.
Speaker Change: Yes, Thanks, Colleen I'll, let <unk> go into the details of that from the futility analysis right.
Speaker Change: Yeah, Hey, Thanks, Colin for the question. So there was a futility analysis that was conducted earlier this year.
Speaker Change: And it was specifically based upon efficacy and safety that was observed in the first 61 patients all of whom were followed for 24 weeks for the efficacy. The D. S. M. B had the unblinded data for both SVR 35 in that cohort as well as absolute TSS.
Speaker Change: <unk> efficacy analyses had pre specified thresholds essentially the thresholds are mounted to no worsening for the combination relative to Russell Aetna alone for the safety again. They were also provided the unblinded safety data from that cohort and there was no pre.
Speaker Change: Slide bars for that analysis that was really based upon their qualitative assessment of the totality of that safety data.
Speaker Change: As you noted they passed the futility and recommended that the start that the start you just continues as planned as we are now doing.
Speaker Change: <unk> is now expected to complete in the June July time frame.
Speaker Change: That's helpful. Thanks, and then I believe in prior quarters, you talked about a two point Delta and average T. S S being in a stat Sig range for manifest too.
Speaker Change: But I think on the on your slide you talk about the power and the primary points about a four point delta on TSS. So can you just talk about what you're expecting to need to hit on PFS for it to be a positive study.
Speaker Change: Sure. So great question. So these are just our assumption so with 350 patients we are assuming adult for across the two arms in a standard deviation of 12 for each of these two arms Inc.
Speaker Change: Incorporating those assumptions the overall power for hitting on absolute T. S. Us is going to be greater than 80%. So these are just our assumptions in reality as you know the data can differ we still maintain that a clinically meaningful outcome is just improvement for the combination you know above and beyond what rock solid.
Speaker Change: [noise] alone demonstrates but you know again that four point Delta and standard deviation of 12, or just again, the stat assumptions that drive the overall power.
Speaker Change: Got it that's helpful and if I could squeeze in one more quick one.
Speaker Change: The the enrolment looks to be slightly behind schedule for the phase three mild hybrids with century city could you speak to some of the enrollment dynamics youre seeing thats, putting you kind of towards the bottom half of the ranch things.
Speaker Change: Yeah.
Speaker Change: All right.
Speaker Change: Go ahead go ahead sorry.
Speaker Change: Yeah, sorry, we stepped over each other but.
Speaker Change: Good question again, Colleen units sort of like when we put together the enrollment cards, we were really looking at a lot of data, especially historical trials transform as well as manifest we were getting a lot of information from the sites and really understanding you know sort of that competitive intensity or lack thereof that is occurring in the field of myelofibrosis specifically.
Speaker Change: In this patient population I will admit it's sort of like what we've seen in the last sort of few months, especially in 2025 suggests that it's a little slower than expected you know things are still very robust both from a screening as well as enrollment, but again, a little slower than what we had anticipated.
Speaker Change: Which is what is driving that slight delay in the enrollment timeframe.
Speaker Change: Okay.
Speaker Change: Got it that's helpful. Thanks for taking our questions.
Speaker Change: Thanks Colin.
Speaker Change: Thank you and your next question comes from the line of Memorial Raycroft from Jefferies. Please go ahead.
Speaker Change: Hi, This is Amy <unk> from Laurie. Thank you for taking our questions. We have two questions for the myelofibrosis phase III trials. The first one is can you talk about your assumptions to get into the fall enrollment in this June July we.
Speaker Change: Well you do a press release when you achieved the target enrollment.
Speaker Change: So can you talk more about our.
Speaker Change: The baseline characteristics of the patients today or will you provide more colors on the baselines them when the trial is fully enrolled.
Speaker Change: I have a quick follow up this one.
Speaker Change: Yeah I can take the first part of that you know are our expectations and where we are now is really aligned with that regimen talk to over 80% enrolled we have visibility into a number of people in our screening and prescreening process. So we expect to complete enrollment in the June July timeframe as ratio of assured.
Speaker Change: And when we do complete our target enrollment, yes, we will share that in our press release, maybe for the second part of the question I'll turn that over to Rachel for some of the baseline characteristics that we're seeing in the trial.
Speaker Change: Yeah sure so for the baseline characteristics and then again. This is just a quick snapshot I mean to your question will we provide at the baseline characteristics for the full population, yeah, absolutely and we anticipate being able to do so in the next few months after enrollment is completed.
Speaker Change: That said can you just give a little bit of visibility on the patient population by and large it's going to be similar to our phase one trial I'm again. These are gonna be your JAK naive myelofibrosis patients all of the patients have to have a baseline platelet count above 100 with that said you know, they're a little less cytopenia.
Speaker Change: What we saw in our phase one so their baseline hemoglobin are slightly higher than what we saw in our phase. One also baseline platelet counts are slightly higher than what we saw in our phase one.
Speaker Change: <unk> break down you know buy dips is very consistent with what you would expect for a JAK naive myelocyte fibrosis population I think the one key difference is going to be baseline symptoms scores.
Speaker Change: So in our phase one population, we didn't have any requirement for that baseline T. S us.
Speaker Change: Our phase three we'd do so patients do you need to be symptomatic, we actually have a threshold. So overall you are going to see higher baseline T. S houses for this population again as compared to the phase one.
Speaker Change: Oh. Thank you that's very helpful. On the follow up is can you talk a little about the if you see anything that patient compliance in the daily measurement off the TSA score and how does that compare to your expectations and other myelofibrosis phase III trials and what yeah. That's it.
Speaker Change: Yeah, I can take that one as well so compliance is really good. So this is something that we've been laser focused on from the very beginning of the trial.
Speaker Change: So you know we use in the <unk> pro Gunder and electronic P. R. O vendor, who you know follows the data alerts goes out to the patients were notified if a patient doesn't happen to complete you know one of their daily T. S houses. It just gives us visibility in terms of the data such that if a patient were to.
Speaker Change: Miss something we're able to go ahead and talk to the site and ensure that that patient gets back on track. So overall that compliance we're really happy with that very high compliance on those daily TSS forums in terms of how that's comparing to other trials I don't know I'm not aware of that.
Speaker Change: The data regarding the compliance from other phase III trials, including manifest transform again, you know I got to say I'm very happy with where we are right now with our phase III.
Speaker Change: Okay. That's very helpful. Thank you so much.
Amy Laurie: Thank you Amy.
Speaker Change: Thank you and your next question comes from the line of Centaur from Piper Sandler. Please go ahead.
Speaker Change: Great. Thank you very much two questions if I may.
Speaker Change: Firstly when it comes to multiple myeloma, what really is driving utilization now and what are some potential marketing synergies between the existing sales force.
Speaker Change: If we'd hopefully get positive myelofibrosis later.
Speaker Change: How would that sort.
Speaker Change: Sort of jumpstart yourselves out efforts.
Speaker Change: Thanks.
Ed: Yeah. Thanks, Ed I'll take the second part of that and then I'll turn it back to so I'll need to take the first part.
Ed: When you when you look at our existing commercialization capabilities and the alignment or synergy with with myelofibrosis.
Ed: 80% overlap so a significant number of patients are seen in the community.
Ed: We have strong capabilities across our commercial team across our access team across our global medical and scientific affairs teams I think there's a really high level of synergy that would enable us to move forward rapidly with really minimal additional investments.
Ed: Turning to so I'll need to take the question on the first part about multi myeloma.
Speaker Change: Thanks, Ted for the question. So we were really pleased with the resilience of the team and ability to grow demand in an increasingly competitive marketplace year over year, So 5% growth in in Q1, and as you look at sort of the underlying drivers of that growth.
Speaker Change: Importantly, we were able to grow in the community setting as well as in the academic setting if you kind of break it down into the two settings of care in the community setting we continue to be used as a flexible combination therapy, a convenient oral about 50% to 60% about patients are in.
Speaker Change: That early alliance second to fourth line setting primarily treated in the community a community setting following and anti CD 38 therapy, but also importantly for patients that come to the community that either feel a T cell engaging therapy or just are not ineligible or don't have access to it.
Speaker Change: Now switching to the academic setting we're positioning exposure with our increasing body of evidence in that pre and post T cell engaging therapy, setting and we're seeing increasing use there, which really led to the growth in the academic setting in Q1 euro but yeah.
Speaker Change: Again, there is it's a highly competitive landscape as you know, but we continue to have a unique positioning as a differentiated mechanism of action both in the community and academic settings.
Richard Regiment: And again to reinforce to your second point, what Richard mentioned.
Richard Regiment: Obviously, a high level of synergy in the physicians, we already call on but our capability our infrastructure that we have built in the past five years really sets us up well for a rapid launch in myelofibrosis if approved.
Richard Regiment: Great. Thank you for all that extra color.
Dan: Thanks, Dan.
Richard Regiment: Okay.
Richard Regiment: Thank you.
Speaker Change: And your next question comes from the line of Peter Lawson from Barclays. Please go ahead.
Peter Lawson: Hey, thanks, so much thanks for taking the questions just on the.
Speaker Change: Return products, maybe <unk>.
Speaker Change: So it's 5 million, what's a normal run rate of return product and there are any further risks.
Speaker Change: Revenue total return product in <unk> that we should be thinking about.
Peter Lawson: Yes, Thanks Peter.
Peter Lawson: At a high level, no and I'll get already to go into the details, but I think as a ratio and worry both talk to this really is.
Peter Lawson: 5 million atypical impact from high dose returns and or maybe you can just expand on that.
Peter Lawson: Yes, Hi, Peter So if you think about the return they were to support the Boston launch, which we talked about which was really ourselves in 'twenty. One 'twenty. Two so if you think about it that's over $220 million in sales and this impact was less than 2%. So.
Peter Lawson: And then when you look going forward I think it's important to know that these atypical returns with high doses.
Peter Lawson: This is the expiry window that opened for the these returns going forward and behind you mentioned it translates more to the 40 in this 60 milligram doses that we're seeing so we don't expect this to carry on into future quarters and so we really do believe this is isolated to this quarter when the window.
Peter Lawson: Opened and relative to all of the sales it still was below 2% and then we expect going forward, we'll continue to kind of get back to our more historic levels that we see it pretty well. So this is more in the 40 and 60 milligrams.
Peter Lawson: Thank you.
Peter Lawson: You mentioned about extending our cash runway.
Peter Lawson: Moshe how are you thinking about for green.
Peter Lawson: Green.
Peter Lawson: This is development.
Peter Lawson: Instructions.
Peter Lawson: So it's a very important question how are we planning extending our cash runway I mean, we understand the importance of being well capitalized and as Richard mentioned and I. Both mentioned on the call. We are exploring various alternatives to extend that cash runway will continue to evaluate our cash runway and Pi financial.
Peter Lawson: Mission basically how else can we deliver these phase III clinical trials and get to these top line data readout.
Peter Lawson: But beyond that I cannot really provide specific details at this time.
Peter Lawson: Got you okay. Thanks, so much.
Peter Lawson: Thank you Peter.
Speaker Change: Thank you and your next question comes from the line of Jonathan Chang from Leerink Partners. Please go ahead.
Yes.
Speaker Change: Hi, This is Albert Augustine is dialing in for Jonathan Chang. Thanks for taking my question will you be able to give us the reasons for confidence that you can still reach your revenue guidance. Thank you.
Speaker Change: Yeah.
Speaker Change: Yeah, I think as you heard from from.
Speaker Change: So on you and you heard from Laurie.
Speaker Change: We're guiding towards the lower end of our revenue guidance given the impact is 5 million impact of atypical Idose returns.
Speaker Change: You heard with regards to our our U S business.
Speaker Change: 5% demand growth and year over year, we heard very strong growth from our global partners.
Speaker Change: So we believe we're going be seeing ourselves deliver in the lower end of our guidance from our global revenue perspective, and from a U S revenue perspective.
Speaker Change: Thank you that's very helpful.
Speaker Change: Thank you.
Speaker Change: Okay.
Speaker Change: Thank you.
Speaker Change: Once again should you have a question. Please press star followed by the ones on your telephone Keypad. Your next question comes from the line of friend Ann brands.
Speaker Change: From RBC capital markets. Please go ahead.
Speaker Change: This is Kevin on for Brian Thanks for taking our questions I just had a follow up on the futility analysis.
Speaker Change: Can you remind us if this was pre specified before this study expansion and co primary endpoint change and of course, if it was something maybe that the FDA.
Speaker Change: Just asking about what the protocol Amendment and then just sticking with FDA have you had any further interactions with the agency in the meantime, and just maybe how would you characterize those interactions. Thank you.
Speaker Change: Yeah. Thank you Kevin I can take that one so yes. This was pre specified in this futility analysis was part of the trial from the very beginning so from the initial protocol.
Speaker Change: Nothing that has happened either what the endpoints or even in the increasing the trial size from 300 to 350, you know prompted.
Speaker Change: Incorporation of asking utility analysis.
Speaker Change: In terms of the FDA conversations I'm, you know sort of like you know as we've mentioned in the past the bulk of them are really around that endpoint change specifically the changed from TSS 50 to absolute T. S. S. You know no additional conversations I'm you know at this time and we're just again looking forward to completing enrollment and.
Speaker Change: You know providing topline results at the end of this year beginning of 'twenty six.
Speaker Change: Okay.
Speaker Change: Great. Thank you.
Speaker Change: Yeah.
Speaker Change: Thank you.
Speaker Change: There are no further questions at this time I would now hand, the goes back to maybe strike colson for any closing remarks.
Speaker Change: Thank you operator, and once again, thank you everyone for joining us today as you heard through the call. We're very focused and very excited about the transformational opportunity. We have ahead of us.
Speaker Change: In myelofibrosis very much in the near term as the team's focus on completing enrollment through June July and reading out the top line data through the end of this year or early next year. The consistency, we see and the strength of our data at Rushmore share. It again today in our <unk>.
Speaker Change: A difficult to treat.
Speaker Change: More severe patient population with multiple lines of therapy is continue to build our confidence.
Speaker Change: The strength and the potential for Selinexor, plus rux, so letting up to become the new standard of care pending positive data and.
Speaker Change: In JAK naive patients. So once again, thank you for joining us.
Speaker Change: Thank you and this concludes today's call. Thank you for participating you may all disconnect.
Speaker Change: Oh.
Speaker Change: Yes.
Speaker Change: Yeah.
Speaker Change: Okay.
Speaker Change: Sure.
Speaker Change: Yes.