Q2 2025 Karyopharm Therapeutics Inc Earnings Call

Good morning. My name is Ludy, and I will be your conference operator. Today, at this time, I would like to welcome everyone to the Karyopharm Therapeutics Q2 2025 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 conference over to Brendan Strong, Senior Vice President of Investor Relations and Corporate Communications. Please go ahead.

Good morning.

Thank you for joining us on today's conference call to discuss Karyopharm Therapeutics' second quarter of 2025 financial results and recent company progress.

We issued a press release this morning, detailing our financial results for the second quarter of 2025.

This release, along with a slide presentation that we will reference during our call today, is available on our website.

For today's call, as seen on slide 2, I'm joined by Richard Paulson, Sohanya Cheng, and Lori Macomber, who will provide an update on the results for the second quarter of 2025 and discuss 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 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 these forward-looking statements as a result of various important factors, including those discussed in the risk factor section of our most recent Form 10-Q or 10-K on file with the SEC, and in other filings that we may make with the SEC in the future.

Any forward-looking statements represent our views as of today only.

While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so. So, even if our views change,

Therefore, you should not rely on these forward-looking statements as representing our views as of any later date. I'll now turn the call over to Richard. Please turn to slide 4.

Thank you, Brandon, and thank you all for joining us today for Karyopharm Therapeutics Inc.'s Q2 2025 earnings call.

Before we begin, as outlined on slide 5, I want to address a topic that is on the minds of our employees, our partners, and our investors.

We are operating in a period of financial constraints with a near-term debt maturity in October.

We are actively engaged with our lenders and advisers to enhance our liquidity and maximize value.

Importantly, the fundamentals of our business remain strong, with a profitable multi-million-dollar commercial organization that provides us with a solid foundation.

That we can build on with two potentially transformative phases, three readouts expected over the next 12 months.

These trials target diseases where patients have few treatment options and there is an opportunity to improve on existing therapies.

Based on the strength of our day-to-day operations, we believe we have the potential to redefine the standard of care for these patients.

With that, let's get into our results. For the quarter, we delivered solid commercial results and made exciting progress towards enrolling in our pivotal Phase 3 trials in myelofibrosis and endometrial cancer.

I am pleased to report that we expect to close new patient screening this week in our Phase 3 Century trial in patients with JAK-naive myelofibrosis.

This is a major milestone that is the result of many years of hard work and dedication from people throughout our organization, and I thank all of our teams.

We greatly thank the patients and clinical trial sites that are participating in Century.

Importantly, Sentry will be our first Phase 3 trial REO, where we utilize a lower dose of cell and XOR combined with anti-Medics during the first two cycles of treatment to improve the tolerability of selling next door, as we work to enhance the patient experience.

Through our strong clinical trial execution, we are seeing the benefits of both of these factors in the preliminary, blinded safety data that Raishma will review today.

We are eagerly anticipating topline data in March of 2026.

Turning to slide 6, completing enrollment in our Phase 3 Sentry trial is an important step in our over seven-year journey to demonstrate the role that XPO1 inhibition may play in patients with mild fibrosis.

The Phase 3 trial caps a growing body of evidence that has consistently demonstrated the potential for XPO1 in myelofibrosis.

We are optimistic about the potential for sale. And next door, plus Rox, to refine and redefine the standard of care for patients living with this disease. Pending positive data, this represents the transformational opportunity for our organization.

As outlined on side 7, given the opportunity to improve the standard of care leading to KS, including Dr. John masquerading, as from Mount Cyanide, who is the principal investigator for Century, continue to highlight the need for new treatment options for patients with myofibrosis.

The depth and durability of response that Dr. Maserin has mentioned in a recent interview with a patient advocacy organization plays to the strengths of cell and Xor.

Finally, as shown on slide 8, we estimate the peak revenue potential for Selinexor in myelofibrosis is up to approximately $1 billion annually in the U.S. alone.

And believe that commercial uptake would be rapid.

We are very eager to bring this combination therapy to the market based on the outcomes of our data and future regulatory approvals. Now, I'd like to turn the call over to Reshma.

Thank you, Richard. I will be sharing new blinded preliminary safety data with you today from our phase 3, Country trial, that may support the potential of the combination of selling next door plus Rexall lnib, which may have a similar if not more favorable, safety profile than Rexall, at nib alone,

Before I get into the new data, let's review why we believe selling an XPO1 inhibitor is a rational mechanism to evaluate in patients with myofibrosis, starting on slide 10.

Felix prevents the nuclear export of various proteins and messenger RNA molecules, thus inhibiting both Jack and non-jackpot.

An important tumor suppressor in myofibrosis. Given that approximately 95% of myofibrosis patients are p53 wild type.

As Richard indicated, we believe that the combination of selenexor plus ruxolitinib has the potential to establish a new treatment paradigm for myelofibrosis patients by addressing each of the four key pillars of this disease, as outlined on slide 11. While no assurances can be given, our confidence continues to strengthen as we receive and review additional data, including updated blinded safety data that I will be reviewing shortly.

Stage. There has been a lack of new treatment options. Given that JAK inhibitors are the only approved class of therapies.

Buxal lnib has been the standard of care for over 13 years.

As the potential first combination therapy in myelofibrosis, the next option, or plus ruxolitinib, would be a convenient all-oral therapy that the myelofibrosis community has clearly indicated interest in adopting, given the rapid, deep, and durable spleen reductions and symptom improvement observed from the Phase 1 study.

First, spleen volume reduction. I think it is a very helpful reminder that only approximately one-third of patients achieve a spleen volume reduction of greater than 35% with the rule in a balloon. Our Phase 1 data suggest that the combination could more than double the SVR 35 rate, with durable responses also seen.

Second is symptom improvement data from our Phase 1 trial of selenexor in combination with ruxolitinib, which showed an average 18.5-point improvement in absolute TSS at week 24. This suggests this combination could provide a meaningful improvement over the 11- to 14-point improvement achieved by patients on ruxolitinib, as observed in the Phase 3 MANIFEST-2 and TRANSFORM-1 trials.

Third is hemoglobin stabilization and transfusion burden.

The data that we presented in June at EHA showed higher hemoglobin levels, a lower transfusion burden, and much lower rates of all-grade and grade 3+ anemia in myelofibrosis patients previously treated with JAK inhibitor therapies. These patients were randomized to selinexor compared to the physician's choice arm, which included retreatment with JAK inhibitor therapies, including ruxolitinib.

Fourth is disease modification. There is minimal evidence of disease modification with Jak inhibitors, as observed from selenexor monotherapy studies in a pre-treated myelofibrosis population, as well as our Phase 1 combination data and Jak inhibitor-naïve myelofibrosis.

Suggest meaningful reductions in key Saito that are critical to myelofibrosis pathogenesis, symptoms, development, and anemia, as well as improvements in bone marrow fibrosis, which increases in arthritis progenitors and mutational burden.

Turning to slide 12, we are pleased that our Phase 3 Century trial will be closing new patient screening this week. Importantly, based upon an initial review of the baseline characteristics of the patients enrolled to date, they are representative of the intended patient population.

One notable characteristic is the baseline TSS, which, when excluding fatigue, may ultimately be higher than in other Phase 3 trials. An important trend that may suggest our trial could be well positioned to report a greater improvement in absolute TSS.

In this new era of combination therapies, there have been challenges demonstrating meaningful symptom improvement above and beyond rule NIB based upon learning from other trials. We believe we have optimized Sentry for success.

First, we changed the co-primary endpoint of TSS 50 to Absolute TSS, a more sensitive method by which to detect meaningful symptom improvement above and beyond rule nib. Second, we have excluded the fatigue domain in the primary analysis of Absolute TSS in alignment with the U.S. FDA due to the difficulty in accurately assessing changes in this symptom.

We are certainly not the first to exclude fatigue. In fact, both the pivotal trials that led to ruxolitinib and fedratinib approvals also excluded fatigue in their TSS 50 analyses.

It's also important to keep in mind that all of our studies have excluded fatigue and symptom analyses, including our Phase 1 study evaluating the combination of cell and XOR, and ruxolitinib, as well as MFO 35, which evaluated cell and XOR as a monotherapy in previously treated MF patients.

Finally, absolute TSS in the Phase 3 Sentry trial will be analyzed using the mixed models repeated measure approach, or MMRM.

This differs from our Phase 1, which, given the limitations and sample size, could only evaluate the mean or average change at week 24.

MMRM is viewed as a more sensitive and potentially more robust method by which to analyze absolute TSS.

The co-primary endpoints in the Century trial are Str 35 and absolute TSS, which are tested sequentially. Some of the key secondary and exploratory endpoints that will also be analyzed include progression-free survival, overall survival, hemoglobin stabilization, variant allele frequency reduction, improvement in bone marrow fibrosis, and changes in cytokine levels.

The data on slides 13 and 14 are from the first 61 patients that enrolled in the Phase 3 portion of the study, who have now been followed for a median of over 12 months. These patients were included in the successfully passed utility analysis conducted at the beginning of the year.

While only members of the DSMB had access to the unblinded efficacy and safety data from these patients, we have continued to track the safety events over time and took a snapshot of the blinded safety data from these 61 patients on July 1, 2025, which continued to look favorable.

Let's start by reviewing the adverse event summary on the left slot side of slide 13.

The data on the 61 patients shown in the table include patients randomized to either the combination of Selenexor plus Rexulti, or Rexulti in a 2 to 1 ratio.

Because these are blinded data, we do not know the rates by each arm. The second and third columns provide the treatment-emergent adverse event summary, or TEA summary, following a median follow-up of more than 7 months or 12 months, respectively.

What you see in the summary is that many of the adverse events occur early, with no meaningful increase in rates after the median of 7 months of follow-up.

In an effort to improve comparability, we then took our analysis one step further.

Knowing that the 61 patients were randomized to 1, we use the historical data on ruxolitinib to extrapolate the preliminary safety data for the approximately 40 patients that received the combination, which is shown in the blue boxes on the right side of the slide.

As you can see, the percentage of patients that have had at least one T is approximately 97%, similar to what has been described for ruxolitinib.

However, when we focus on the grade 3 plus TEAEs, the extrapolated data suggests that the rate may be slightly lower for patients on the combination versus ruxolitinib, at approximately 53% and 57%, respectively.

Looking at serious treatment-emergent adverse events (TEAEs), the extrapolated data suggests an even greater benefit for the combination therapy than for ruxolitinib. Finally, the extrapolated rate of TEA leading to treatment discontinuation is only 5% to 7% for the combination, which is lower than the 6% to 11% range that has been historically reported for ruxolitinib, and we view this as an encouraging observation.

Let's turn to the individual treatment emerging address events, as shown on slide 14. We took the same approach with these data as the ones I just described on the prior slide.

Starting on the left, you'll see the all-grade blinded safety data on the 61 patients, with a median follow-up of more than 7 months. And again, for more than 12 months,

We also show 2 notable grade 34 teas at the bottom left: anemia and thrombocytopenia.

Consistent with what I described on the prior slide, we see most AES occurring within the first 7 months of follow-up.

Additional events are observed with the passage of time, resulting in the rates of TAEs modestly increased at 12 months of follow-up.

The number that excites me the most is the extrapolated rate of Grade 3-4 anemia at approximately 26%. The extrapolated rate of Grade 3 for anemia for the combination is meaningfully lower than the 37% historically reported for RXL Inhibitor. While the extrapolated rate of all-grade nausea is higher in the combination arm than ruxolitinib, the approximately 64% is substantially lower than the approximately 80% rate that we reported in the Phase 1 portion of this trial.

We have recently presented compelling Saito data that could explain, in part, the efficacy observed with cell and XOR. In addition, slide 15 shows pictographs of bone marrows evaluated at baseline and at week 24 from a patient treated with the selenexor, raxaul, LNIB combination, and is further evidence of the potential disease modification that selenexor may induce in patients with myofibrosis.

These data were first presented by Dr. Harris Ali at the International Congress on Milo, Proliferative Neoplasms in October 2024.

This Jak inhibitor-naïve Milo fibrosis patient was treated with selenexor 60 milligrams and ruxolitinib 15 milligrams twice a day, as per the U.S. PI.

The ruxolitinib dose was decreased to suboptimal ruxolitinib doses, 5 milligrams twice a day, starting in Cycle 2.

The patient achieved an SVR 35 as early as week 12 and a TSS 50 as early as week 8, as a result of symptom reduction from a baseline of 42 points to 19.5 points at week 8.

The efficacy observed in this patient can be explained in part by the meaningful change occurring in their bone marrow. Specifically, a 46% reduction in fiber density was assessed by digital pathology at week 24 compared to baseline samples. There was also approximately a 200% increase in arthritis progenitors, which are precursors of mature red blood cells.

While this is a single patient experience, the increase in arthritis progenitors could also explain the potentially lower grade 3-plus anemia rates with the combination, as compared to historical ruxolitinib data, as I explained on the previous slide.

We are very encouraged about these data and what it could mean for patients. If we see something similar in the topline results in the Phase 3 Century trial.

Specifically, it could suggest a combination therapy that has a safety profile similar, if not potentially better, than standard of care, Rexle and LNIB.

Given that both grade 3 plus anemia and thrombocytopenia are the same, if not better than ruxolitinib balloon, it could also suggest decreased blood draws for the patient and reduced monitoring burden for physicians and healthcare staff.

I would also like to provide an update on our Phase 2 Century 2 trial, where we are evaluating cell and xor as monotherapies in JAK inhibitor-naive myelofibrosis patients with moderate thrombocytopenia.

Enrollment in this trial has been slower than anticipated, given that the vast majority of sites enrolling on Century 2 are also enrolling patients into Century. We have asked sites to prioritize enrollment on Century.

In addition, patients with platelet counts between 50,000 and 100,000 represent only 10% to 15% of all JAK-naïve myelofibrosis.

Now that SENTRY enrollment is completing, we plan on expanding the enrollment criteria to include all patients with platelet counts above 50,000, pending they meet all other eligibility criteria. This should increase the number of patients that can participate in this trial.

Our prior plan was to report preliminary data on a subset of patients from Sentry 2 in the first half of this year.

Given the enrollment challenges and the changes we are making to the enrollment criteria, we now plan to report topline data from all patients that we enroll in the 60 milligram cohort of this trial in 2026.

Now, let's shift our focus to endometrial cancer, where p53 wild type is such an important biomarker.

As seen on slide 17, patients with both MMR proficient and TP53 wild type tumors make up approximately 50% of all advanced or recurrent endometrial cancer cases, representing a very sizable group. Enrollment in the EXPORT ECO 42 trial is progressing steadily, as seen on slide 18, and we continue to expect to report topline data in the middle of 2026. I remain encouraged with the potential of Solenexor to achieve clinically meaningful outcomes in the maintenance setting for patients with TP53 wild type endometrial cancer.

Lastly, our Phase 3, EMN 29, SPD trial is outlined on slide 20. This trial aims to demonstrate the potential of an all-oral, triplet treatment option for multiple myeloma patients that could also benefit those undergoing pre- and post-T cell engaging therapies.

We expect to report topline data from this event-driven trial in the first half of 2026. I will now turn the call to Sohanya Cheng.

Thank you, Reshma Rangwala. On slide 22, I will discuss our commercial highlights for Q2 2025. Net product revenue was $29.7 million for this quarter, up 6% from the second quarter of 2024.

Demand for exposure was consistent in the second quarter of 2025 versus the second quarter of 2024, with the community setting continuing to drive approximately 60% of total U.S. sales.

As we all know, the multiple myeloma market is highly competitive and is becoming more competitive each year.

Positioned in the community as a flexible therapy with a differentiated mechanism of action, oral convenient option, following treatment with an anti-CD38 therapy, as well as in patients who cannot access or fail a T cell engaging therapy.

In the academic setting, exposure is being increasingly used before and following T cell therapies.

Taking our results for the first half of the year into account, including the atypical level of returns. In the first quarter of this year, we expect net product revenue for the full year 2025 to be in the range of $110 million to $120 million.

Finally, we continue to expand global patient access for selling Xor and are now approved in various indications in 50 countries.

This is translating into growth in royalty revenue from Menarini, antigen, and other international partners.

Royalty revenue increased 28% to $1.6 million in the second quarter of 2025 compared to the second quarter of 2024, reflecting increased global demand for Xpovio and Nexpo.

With data from a phase 3 Century trial in sight, our commercial team is preparing for a very rapid launch in mallow fibrosis, if approved.

As outlined on flight 23, 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.

If you think about this opportunity, keep in mind that the average real-world duration for the current standard of care is approximately 13 months.

And given the data we have reported to date, we believe we may have an opportunity to extend this further when Rock Solid is combined with selling Xor.

On slide 24, we outline why we believe we're well positioned for a rapid launch in the treatment of fibrosis, pending positive data and approval.

As we've shared previously, 75% of the physicians that we surveyed say that they intend to adopt a combination therapy inmallow fibrosis, if one becomes available.

If we sell an ex or if it is approved in combination with Rock to Lizin, we could be the first combination therapy on the market.

We would be at all oral therapy, which makes adoption much easier, especially in the community setting.

On this point, there's an 80% overlap in the community between milo fibrosis and multiple myeloma prescribers that our organization is already calling on, which enables us to drive a rapid launch and minimizes the upfront investment required for the launch.

Finally, in endometrial cancer, as shown on slide 25, we continue to believe that we have a significant opportunity in the p53 wild-type and pMMR patient population, which represents approximately 50% of advanced or recurrent endometrial cancer patients.

Similar to what I outlined for the model of fibrosis, there is a large overlap between the potential community-based oncologists caring for endometrial cancer patients and those we are already engaging with.

Now, I'll turn the call over to Lori.

Good morning, everyone, and thank you, Saha.

Turning to our financials.

Since we issued a press release earlier today with the full financial results, I will focus on the highlights and review your guidance for 2025 on slide 27.

Total revenue for the second quarter of 2025 was $37.9 million, compared to $42.8 million for the second quarter of 2024.

The decline was primarily attributable to $6 million of non-recurring license-related revenue from our partners recognized during the second quarter of 2024.

Us Expo, net product revenue for the second quarter of 2025 was $29.7 million compared to $28 million for the second quarter of 2024.

As expected, the rate of product returns this quarter reverted to historic levels following the atypical increase reported in the first quarter of this year.

24.

The year-over-year decline was primarily driven by mix and lower 340B discounts in the second quarter of 2025.

We expect our gross to net provisions will remain relatively consistent with Q2 2025 for the remainder of the year.

R&D expenses for the second quarter of 2025 were $32.8 million, down 15% when compared to $38.4 million for the second quarter of 2024.

The decrease was due to a reduction in headcount and contractors related to our cost optimization initiatives, combined with lower clinical trial and related costs, primarily from our Phase 3 clinical trial and multiple myeloma.

SGNA expenses for the second quarter of 2025 were $28.5 million, down 8% compared to $31.1 million for the second quarter of 2024.

The decrease was primarily due to the realization of previously implemented cost reduction initiatives.

Interest expense was $11.2 million in the second quarter of 2025, up from $8.9 million in the second quarter of 2024.

As a reminder, we announced a refinancing in the second quarter of 2024 that raised interest expense. However, there was only a partial quarter impact in the second quarter of 2024.

Last year's refinancing also resulted in a $44.7 million gain on the extinguishment of debt in the second quarter of 2024.

Other expense was $2.2 million in the second quarter of 2025, compared to $14.3 million of other income in the second quarter of 2024.

These amounts were trivial to reoccurring. Non-cash fair value. Remeasurement of derivatives and liability classified. Common stock warrants related to the refinancing transactions in the second quarter of 2024.

We reported a net loss of $37.3 million, or $4.32 per share, on a GAAP basis.

This figure includes $11.2 million in interest expense related to our debt instruments, as well as approximately $2,000 in non-cash losses from the re-measurement of embedded derivatives and liability-classified common stock warrants.

Our net loss from operations was 24.5 million for the second quarter of 2025.

This operating result reflects the performance of our core business during the quarter.

From an earnings per share perspective. Our gaap EPS includes both interest expense and mark-to-market impact of the warrant and derivative remeasurement.

We continue to be very diligent in allocating our resources and pipeline prioritization.

We announced a roughly 20% reduction in our workforce in early July.

You will start to see the financial impact of these actions when we report our results for the fourth quarter of this year.

In 202026, we expect these actions will lower our annual spend by approximately 13 million.

We exited the second quarter of 2025 with cash cash. Equivalents restricted cash and Investments of 52 million compared to 109.1 million as of December, 31st 2024.

Based on our current operating plans, our guidance for the full year of 2025 is as follows.

Total revenue of $140 to $155 million, consisting of U.S. exposure, net product revenue, and licensed royalty and milestone revenue, is expected to be earned from our partners, primarily Medori and Antigen.

U.S. exposure, net product revenue is expected to be in the range of $110 million to $120 million.

R&D and SG&A expenses are expected to be in the range of $240 million to $250 million.

And finally, we expect our existing liquidity, including the revenue we expect to generate from Xpovio net product sales.

As well as revenue generated from our license agreements will be sufficient to fund our plan operations to the October 15th maturity of our senior convertible notes.

26.

As we address this, we are working closely with our advisors including Centerview Partners to explore potential financing, and strategic alternatives to enhance liquidity and maximize value.

I will now turn the call back to Richard for some final thoughts.

Thank you, Lori.

Turning to slide 29. We continue to believe that mile fibrosis and endometrial cancer. Depending on the data from our ongoing phase 3, clinical trials are both game-changing opportunities for patients and our organization. With the myofibrosis opportunity alone representing up to a potential 1 billion in Peak annual revenue in the us alone.

To deliver on these opportunities, we are working with urgency and discipline to address our liquidity while keeping our focus squarely on the opportunity in front of us to bring meaningful, much-needed innovation to patients and generate significant value.

I would like to thank our employees, our partners, and our investors for their continued support and belief in our potential.

We look forward to updating you on our progress in the coming months.

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

Thank you. And ladies and gentlemen, we will not begin the question and answer session to ask a question. You may press the star, followed by the number 1 on your telephone keypad. If you're using a speaker-phone, please pick up your handset before pressing the keys to withdraw your question. Please press star 2. We ask that you please name. It yourself to 1 question and 1 follow-up with that. Our first question comes from the line of 10 102 with Piper Sandler. Please go ahead.

Great. Thank you so much for uh, taking my question. Um,

I, I guess my biggest question has to do, really, too, if I met first just on, um, My Little fibrosis.

You know, everything seems to be pointing in the right direction. What's what's your biggest worry about that potential read out? Um, is it Jack if I doing better is there? What what's, what could be kind of the snake hiding in the bushes or the grass, or whatever, that could surprise us? And then the second question is just with, really 3, big readouts, next year, with Modelo fibrosis, um, the export, um, MMO 31 trial and also endometrial

How are you planning on sort of prepping and being ready for all of those data readouts? At the same time, is that going to cause any problems just in terms of the process?

Processing everything. Thanks so much.

Yeah, thanks, Ted. Uh, a couple of great questions. I'll take the second one first.

And that that's a, a great opportunity that we're excited about to have 3, big readouts, uh, in front of us and to be getting ready uhhh for potentially positive data across all those readouts, uh, is what we're super excited about as an organization. Obviously, you know, building on the foundation and multiple Myoma. Uh, I think that's, that's, uh, something which is kind of, our bread, and butter organizations really ready for

Mi fibrosis, uh, is a key area for us obviously. And you've heard us talk. Uh, and we talked again today that, you know, there's significant overlap in the prescriber base. So to be able to build on our foundation leverage, our commercial capabilities, uh, and and get out and start. Um, being able to get ready for for my oh fibrosis and also my launching it. You know pending positive data again. I think we're we're well ready for and then

You know, endometrial cancer going to largely the same. There's a lot of overlap because a number of these patients both in my fibrosis and endometrial, cancer are seen in the community. So our organization, our payer capabilities are our medical Affairs capabilities. Our commercial capabilities. All have a lot of synergy to be able to bring both myofibrosis and endometrial cancer to the patients rapidly. So that's a good problem that we're excited about. Uh, and you know, the organization already is starting to work on uh, getting ready for my fibrosis. Obviously is our our next potentially transformative opportunity. And, uh, we're looking forward to updating more on the future and for the, for the second part of the question, I'll turn that over to rishma kind of talk with you about MF, you know, our our I talk about our, our biggest worry. Um I think there's just you know, broadly I'll say is just

That's being put in place with rule nib and so, to be able to, potentially combine with the standard of care and create a new standard of care for patients, obviously, is is very exciting for us, especially, you know, given that, that's an all oral with 2 already approved medications, um, but I'll let RMA maybe share with you, what what her biggest worry is, uh, with regards to looking at the, the phase 3 read out with the cell next door and Rule it nib.

Yeah, thanks Richard and thanks. Ted for the question. Um,

You know, it's interesting worry. I'm not sure I would, um, couch it in those words, you know, as Richard was mentioning, right? We've been exploring Milo fibrosis for so many years. I mean, 7 plus years, both with pre-clinical data, obviously, teasing apart the mechanism. We've got multiple clinical data sets. Um, we've got a phase 1 Study, evaluating the combination and this relevant patient population of Jack naive Milo fibrosis. And I have to say, I like, what we've got right, you know, we've shown some very very compelling.

Spr data S35 at week 24 showed more than doubles what we've observed with historical Rock, and salit nib that leads to SVR rates. Only approximately a third of all patients have experienced symptom improvement. And, I'll admit, right? Symptom improvement has been the Achilles' heel of so many Phase 3 trials. With that said, ...

I like the data that we've observed today. Both from a TSS 50 standpoint and also an absolute TSS ladder, which shows an 18.5-point improvement at week 24 relative to baseline.

And again, I always contextualize that with some of the monotherapy data that also shows some very compelling TSS data as well.

But beyond that, right, you know, SDR and TSS are only two of the key hallmarks that we evaluate in myelofibrosis. You know, I really am quite encouraged by the disease modification data, both with the Saito as well as bone marrow fibrosis. Obviously, the impact on.

Hemoglobin stabilization is a really intriguing observation that we're also including, improving the safety, especially the grade 3 plus.

Anemia rates relative to historical control. So I think, like, when I step back, right? I mean, the Phase 3 is going to be the Phase 3, but I think going into that Phase 3, I really again like what we see in that, you know, the combination really can meaningfully improve on not only the key endpoints of SVR, 35, and absolute TSS, but all of the areas that obviously are very relevant to the patient as well as their physician.

That's very helpful, and I share your enthusiasm. I'm so looking forward to the data readouts. Thanks so much.

Thank you, Dad.

And your next question comes from the line of Colleen Cruz with Beard. Please go ahead.

Great. Good morning, thanks for taking our questions. Uh, hopeful update on the baseline characteristics for the pivotal MF combo study. You spoke to higher TSS at baseline. Can you talk about that a little bit more and how you think that will impact the results? And specifically, have you seen a feeling of effect with other trials?

Yeah, thanks Colleen. Um, great question. So you know, some of the data especially when we look at historical trials in this Jack naive Milo fibrosis, it does suggest whether you're looking at psss 50 or absolute PSS but the higher the Baseline, right? The more likely you're going to see that meaningful outcome, either a 50% Improvement or that proportion of patients, who can achieve that, 50% Improvement or overall, that average reduction. And that means TSS at week, 24 relative to Baseline. So the higher you can push it, the more likely again, you can achieve

A meaningful outcome. Um, and so, you know, again, these are just preliminary characteristics; we have not enrolled all of our patients. So, you know, ultimately, when we complete enrollment, we'll take a snapshot of where that baseline TSS is, but I'm really encouraged by where the evolution has been within this Phase 3 trial.

But can you just further explain the rationale again for why you think you're seeing lower rates of grade 3 for anemia with the combination? And how important do you think that will be for physicians and, you know, potential uptake of the combination?

Yeah that it's it's a really really intriguing observation and I really do think that it's probably due to the disease modification that is occurring with Salon X4, plus plus Rockville lnib, you know, we've touched upon some really compelling Saito data. This was back at eha in June, when we looked at sell xor as a monotherapy and that previously treated population, what those data suggested is that it's decreasing. Keyside of kinds that are involved in all aspects of anemia specifically hipside and feritin Etc, right? You see decreases in those rates, um, obviously, or, or potentially could be translating to lower grade 3, plus anemia. I'm really liking with what we see from the very preliminary data coming out of the bone marrow fibrosis too. You know, a really Market decrease in that reticulum density, it suggests that you're clearing out that marrow, um, and, you know, potentially allowing for some repos.

Population of those key, uh, cells that ultimately can produce, you know, a risk for sites and lead to higher hemoglobin. So that also could not only lead to efficacy, eer hemoglobin, but also potentially translate to lower grade 3 plus rates early days, right? These are just hypothesis-generating data. Um, but I love the fact that we see these clinical outcomes married with these disease modification data that again can explain both the efficacy and safety aspects that we see in our trials.

Great, thanks for taking our questions.

Thank you, Colleen.

And your next question comes from the line at Peter Lawson with Barclays. Please go ahead.

Great. Thank you so much. Thanks for the updates. Um, and just as we think about revenues and um,

Kind of the drive is what was the contribution I made, this pricing, this inventory. And then how should we think about that for the rest of the year? And then I have a follow-up.

Yeah, thanks, Peter. Um, yeah, inventory was relatively consistent across the period, so I think as soon as you shared, you know, there's a balance. We saw an improvement in the GTN.

Uh, and that's something that we obviously, you know, talked to last quarter, when we had this 1 time, you know, returns issue and and so overall we also have seen demand be relatively consistent but that's kind of the balance in the in the drivers.

Great, thank you. And then, um,

At that early blinded safety data looks, you know, really encouraging to lower grade 3 anemia and discontinuation rates. This is Rex Alone. Um, how confident are you that those kind of backing out of the data sets were kind of hold once it's a blinded?

It's a, it's a good question and Peter, I always say, I wish I had that perfect crystal ball. Um, sometimes crystal balls can be fuzzy, but with that said, I like the evolution that we've seen in these blinded safety data.

You know, we've taken a couple of snapshots, so we've taken advantage of these 61 patients. They again were included as part of that futility analysis that the Data Safety Monitoring Board evaluated earlier this year with approximately 6 months of follow-up. We see a really nice evolution in that safety profile, especially when we extrapolate with historical Rexall LB. And when we continue to follow this patient and took an updated snapshot, as of July 1st, we really see a similar kind of trend. Yes, numerically, we do see.

So you know, ultimately we'll need to just see what the Phase 3 data demonstrate. Um, but again, encouraged by this preliminary observation.

Great, thank you so much.

Thank you, Peter.

And your next question comes from the line of Murray Raycroft with Jeffrey. Please go ahead.

Hi, uh, this is Amy. Um, for me uh thank you for taking a questions and congrats on the quarter. I have 2 questions 1 on the endometrial or the other on the Central 2 study. So for the individual phase 3, uh, can you talk about the enrollment progress so far and what percentage of the target has already been enrolled and for the century 2, uh could you help us understand how the protocol Amendment would help with enrollment of the study considering, you know, the phase 3 century and this original Century to a knot in the same population and what is the bar for Success? Now for this amended study and what do you plan to show in the top line and how should we contextualize the data with the new, uh population?

Thanks.

No. Thanks Amy. So, I'll take the first 1, uh, for endometrial cancer. So, enrollment is very steady, right? You know, this is a unique study and that the biomarker driven maintenance study, what we are seeing right now and aiming to complete, is that what we call the top of the funnel? Uh, the number of patients, who submitted samples to Foundation me medicine, for assessment of their p53 status. We see nice flows of samples into that bucket, um, you know, and anticipate Topline results in the middle of 2026. So again, very encouraged by the by the progress made to date. Um, we have not released any Target enrollment uh, as as of today. So, you know, we're not giving out any numbers again. We're confident with what we are seeing at the top of the funnel.

As well as the subsequent randomization that we are going to hit uh Topline results in the middle of 2026 in terms of century 2. So another good question. So let me just back up for a minute. It's a century. 2 is also looking at that uh Jack naive Milo fibrosis patient population, we're evaluating cell and xor as a monotherapy in a single arm cohort. Um in this population. Now keep in mind that the population had been different and still is different than our combination trial Century. The ongoing thing

Phase 3 largely based upon their platelet counts. The century 2 is just enrolling patients with h. With who have Baseline platelet counts between 50 and 100 centuries and rolling patients with

What we plan to do. So, this hasn't occurred yet but what we plan to do is, to amend the trial to allow all patients with Baseline. Platelet counts, 50, all the way. There's no limit to enroll as part of this trial. So now that we are opening up that Baseline, platelet cap, we do anticipate that the enrollment is going to pick up relative to what we've seen to date.

In terms of the bar, because the amendment has not been issued yet, we don't see any difference in the bar. So, we do anticipate that the majority of the patients enrolled as part of the 60 mg cohort are still going to be that moderate thrombocytopenic population, 50 to 100. This is a very high unmet need small population at approximately 14% because there's not really effective therapies for that population. That bar is, you know, anywhere above 25%, right? 25 to 30% relative to historical controls of approximately 15%.

Okay, thank you.

Thank you, Amy.

And your next question comes from the line of Brian Abrams with RBC Capital Markets. Please go ahead.

Um, hey. Good morning, guys. Thanks for taking, uh, my questions. Um, I guess maybe asking the safety question a little bit of a different way, I'm curious, like, what's your...

Is, there's been some recent changes in FDA leadership at Cedar, and I'm curious if you had any updated Communications with the agency, uh, since your alignment on the new, uh, co-primary endpoints, uh, for for the phase 3, uh, and your level of confidence that their position on, uh, what's going to be required? Uh, Remains the Same as your prior feedback. Thanks.

Thanks, Brian for the question. So it really is a very nice Evolution. I'm both to historical RX Lita, but as you mentioned also to The Phase 1 data and and arguably, I think

Some of the greatest benefits are around the GI toxicity, which is very well known with Selinexor. But what's what? What we see in our Phase 3 extrapolated data is a really nice improvement, both with nausea and vomiting. So in that Phase 1, yes, we saw, you know, 80% of the patients experience any grade of nausea, with approximately 50% of the patients experiencing...

Any grade vomiting and what we are now potentially seeing in our phase 3 is reduction in both the nausea and vomiting from 80 to 64%, even vomiting from 50 to now you know close to what you see and expect with historical Rexall Litany of around 10 12%.

I think you hit the hammer on the head. Why do we see this? I think it's really because of all of the ante so when our Phase 1, anti- usage was not consistent. So there was many patients. Unfortunately, who did not take dual anti Medics, there were quite a few patients who only took 1. There was some patients who didn't take any in our phase 3. We've really tightened that requirement virtually. All of those patients above 90% are taking those dual anti-immigrant for the first 2 cycles. And then if optional thereafter and I think it's because of those required. Dual anti Medics we see this Improvement in nausea but I think the real really nice Improvement is again in that vomiting, you know, about some 50% all the way down to 10%. So,

A really nice Improvement. Not only to The Phase 1, but again also relative to historical raxaul and nib.

In terms of the FDA. Um, yeah, so lots of evolution going on with the FDA as we all know. Um, you know, with that said, no additional feedback. So, you know, we got that feedback back in, you know, third quarter, um, of 2024 around the endpoint change and have not gotten any additional feedback, because everything is so documented. We feel confident in the position that the FDA will ultimately take on our phase 3, um, when we meet with them, hopefully next year.

And and Brian, I think, you know, and just, just add to that. I think when, when we look at the agency, I think we feel we're a really positive about the evolutions and how they're focused on accelerating, you know, access to meaningful, cures treatments and Diagnostics. And, you know, just a couple months back, we participated in a really valuable CEO listening to her with the commissioner and really appreciate the the interactions. I think and the evolutions. So, continuing to look forward to working positive with them to bring new medicines to patients.

Really helpful. Thank you.

Thanks.

And your next question comes from the line of Jonathan Chang with Ling Partners. Please go ahead.

Hi guys, thanks for taking my question. Uh, can you discuss the scenarios being explored to enhance liquidity and maximize value? What existing and/or potential exposure and opportunities are being considered in these scenarios? Thank you.

Yeah, and thanks, Jonathan. I mean, on that side, you know, there’s really nothing more to add on this point beyond what we've discussed.

Stayed in our 8K in July. And what we share today in the press release and our entertain, thank you.

As we've stated, we are exploring, you know, a full range of financing and strategic alternatives that are going to enable us to extend our cash runway, enhance liquidity, and maximize value.

Uh, we have engaged Interview Partners, which, as you know, is a real leader in this area, to help us through this and.

You know, we don't intend to discuss or disclose any further developments, you know, unless and until our board has approved a real specific action or...

Otherwise, it was determined that further disclosure is appropriate. So that's kind of where we are now, and, you know, continuing to work on it obviously as we move forward. And obviously with Expo View, it encompasses the totality of exposure.

Got it, understood. Thanks for taking the question.

Thanks Jonathan.

Further questions at this time, I would like to turn it back to Richard, Paulson for closing remarks.

Thanks operator. And it goes as you heard today. You know, our organization is very focused on delivering on the opportunities in front of us.

Uh, as we've stated, we're working with real urgency and with discipline to address our liquidity and

Keeping our focus squarely on the opportunities we have in front of us, which is why we do what we do every day: to bring meaningful, much-needed innovation to patients and generate significant value. So once again, I would like to thank our employees, our partners, and our investors for the continued support and the belief in our potential. Thank you for joining the call today.

Thank you to the presenters. Ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.