Good morning. My name is Ludi and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Fourth Quarter and Full Year 2023 Financial Results Conference Call. There will be a question-and-answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Elhan Webb, Senior Vice President of Investor Relations. Please go ahead.
Thank you, Ludi, and thank you all for joining us on today's conference call to discuss our financial results and recent company progress. We issued a press release this morning detailing our financial results for the fourth quarter and full year 2023. 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 two, I'm joined by Richard, Reshma, Sohanya, and Mike, who will provide an update on our results for the fourth quarter and full year 2023 and recent clinical developments. Before we begin our formal comments, I'll remind you that various remarks we'll make today constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995 as outlined on slide three.
Actual results may differ materially from those indicated by these FLS as a result of various important factors, including those discussed in the Risk Factors section of our most recent Form 10-Q or 10-K, which are on file with the SEC, and in other filings that we may make with the SEC in the future. Any FLS represent our views as of today only. While we may elect to update these FLS at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these FLS as representing our views as of any later date. I will now turn the call over to Richard. Please turn to slide four.
Good morning. Thank you, Elhan, and thank you for joining us today for Karyopharm's Q4 and Full Year 2023 Earnings Call. My name is Richard Paulson, President and Chief Executive Officer of Karyopharm. As you can see on slide five, over the past few years, we have been intently focused on positioning ourselves for our next stage of growth with three late-stage trials supported by a growing body of unprecedented data in both solid and hematological malignancies that are expected to read out next year. The data we are seeing in myelofibrosis and endometrial cancer are highly encouraging, and we believe the largest opportunities for selinexor are yet to come. These trials will potentially enhance and create new standards of care for patients and provide significant value creation opportunities in the near term.
It is our top priority to advance this late-stage pipeline, address patients' unmet needs, and if approved, rapidly expand selinexor's use in new indications. We are doing this by concentrating our investments into these pivotal programs and leveraging our existing multi-myeloma franchise anchored on our commercial drug XPOVIO, which is approved in over 40 countries, generating brand profitability and growing experience with physicians. Through ongoing disciplined expense management, we have an expected cash runway into late 2025, providing us with the financial strength to deliver on key data readouts from our three phase III studies. In 2023, we delivered total revenues of $146 million, meeting our guidance for full year, and in 2024, we expect to generate $140 million-$160 million total revenues.
This range reflects the highly competitive nature of the multiple myeloma market, with important new entrants in the second half of 2023 and more anticipated this year, which we are mindful of, especially when setting expectations for our financial performance this year. This is balanced by the resilience we have demonstrated and our focus on both near-term and long-term growth. Importantly, our existing commercial infrastructure is profitable today and provides us with the capability to support the rapid and smooth commercial launch of selinexor in new indications. We are committed to delivering on the opportunities ahead of us and believe selinexor could generate approximately $2 billion of peak annual revenues in the U.S. alone. Turning now to slide six, let's review some key accomplishments from our core programs in 2023, which strengthen our confidence in our ongoing phase III trials.
In myelofibrosis, we are very encouraged by the comprehensive profile, including tolerability, spleen volume reduction, symptom improvement as measured by TSS-50, and the long-term durability that we saw in our phase I data of selinexor plus ruxolitinib in JAK-naïve patients presented at ASH. In endometrial cancer, we are excited by the substantial improvement in median progression-free survival for patients who are TP53 wild type, as reported with the ASCO Plenary Series. This highlights the opportunity we may have to deliver unprecedented outcomes for a large and unique population of patients. In multiple myeloma, despite increased competition in the academic setting, we continued to grow XPOVIO in the community setting and shifted its use to earlier lines of treatment.
We look forward to the results from our phase III trial evaluating selinexor at the low dose of 40 milligrams in combination with the well-established backbone therapy of pomalidomide and dexamethasone post-anti-CD38 antibodies. Turning now to slide seven, as we work to create new standards of care, we expect each of our ongoing phase III clinical trials will read out top-line results in 2025. Any one of these programs, if approved, represents an incredibly meaningful growth opportunity for our company, with endometrial cancer and myelofibrosis representing the largest opportunities. Moving to slide eight, I would now like to turn the call over to Reshma to expand further on our clinical pipeline progress. Reshma?
Thank you, Richard, and good morning, everyone. As Richard mentioned, on slide nine, we have a very promising late-stage pipeline with selinexor in three phase III studies, all of which incorporate selinexor doses at 40 or 60 milligrams once weekly. Let's now turn our attention to myelofibrosis on slide 11. Ruxolitinib remains the standard of care for the majority of JAK-naïve patients. However, there is an opportunity to improve benefit given that the efficacy with ruxolitinib is limited, with only about 35% of patients achieving an SVR35 and less than half of all patients achieving meaningful symptom improvement. XPO1 inhibition is a fundamental mechanism in myelofibrosis given that it targets both JAK and non-JAK pathways, underscoring selinexor's additive, if not potentially synergistic activity when dosed in combination.
We are evaluating the potential for selinexor in combination with ruxolitinib to provide benefit across all of the hallmarks of the disease, including spleen reduction, symptom improvement, disease modification, and stabilization, if not improvement, of the cytopenias. As you can see on slide 12, we presented updated data last year from our trial evaluating selinexor 60 milligrams with ruxolitinib in JAK-naïve patients, which showed an SVR35 of 79% at week 24 in the intent-to-treat population. Importantly, amongst the evaluable patients, 100% achieved an SVR35 at any time. On slide 13, both TSS-50 and absolute TSS showed very meaningful improvements at week 24. 58% of the intent-to-treat and 78% of the efficacy evaluable achieved a TSS-50 response. For absolute TSS, an average 18.5-point improvement was observed in the efficacy evaluable population at the same time point.
Compared these to historical ruxolitinib data, where TSS-50 was observed in 42%-46% of ruxolitinib-treated patients, and the average TSS improvement was 11-14 points. Moreover, on slide 14, we see that all symptom domains are substantially improved with the selinexor combination, with all domains achieving an approximately 50% or greater improvement compared to baseline. The absolute TSS, TSS-50, and individual domain improvements are corroborated by cytokine data, which show that the pro-inflammatory cytokines, which lead to myelofibrosis symptom development, show rapid, deep, and sustained reductions relative to baseline. Taken together, the data demonstrate that the novel combination of selinexor plus ruxolitinib has the potential to maximize symptom improvement relative to ruxolitinib alone in the ongoing phase III study. Shown on slide 15, we find the durability data from the selinexor-ruxolitinib combination very important for patients.
As of the most recent data cutoff, none of the week 24 SVR35 responders dosed at selinexor 60 milligrams had observed radiographic progressions, and none of the week 24 TSS-50 responders had observed symptom progressions. While I acknowledge the apparent limitations in cross-trial comparisons, contrast these data to ruxolitinib alone, in which only approximately 70% of responses were ongoing at 78 weeks. As we move to slide 16, when we look at SVR35 and TSS-50 together, we see that 50% of patients experienced both of these responses at week 24, and 75% experienced both SVR35 and TSS-50 response at any time. On slide 17, we see that in addition to the cytokine data, we also observe signs of disease modification with the stabilization in the hemoglobin levels of patients on selinexor 60 milligrams in combination with ruxolitinib.
This trend is unique with the selinexor combination, given that with ruxolitinib alone, hemoglobin levels drop after treatment initiation and tend to stay low. On slide 18, prominent myelofibrosis leaders in the field are impressed with the profile this unique selinexor combination may provide to JAK-naïve myelofibrosis patients. In fact, one of the most prominent opinion leaders and the principal investigator of the selinexor plus ruxolitinib phase III study, Dr. John Mascarenhas, noted that the combination is tolerable and that the spleen and symptom data observed to date from the phase I study may significantly improve these outcomes in first-line myelofibrosis. As the body of data grow and positively evolve, we maintain a high level of confidence in the ongoing phase III study shown on slide 19, which is evaluating the combination of selinexor 60 mg with ruxolitinib versus ruxolitinib alone in 306 JAK-naïve myelofibrosis patients.
We are on track to report top-line results in the second half of 2025. Turning now to endometrial cancer. As seen on slide 21, there is a paradigm shift underway for the treatment of women with advanced or recurrent endometrial cancer, the most common form of gynecologic cancer in the United States, with increasing use of molecular classification. TP53 wild type represents a potentially unique but fundamental biomarker in endometrial cancer. Today, for dMMR patients who represent approximately 20% of advanced recurrent endometrial cancer, the new FDA-approved standard is dostarlimab in combination with chemotherapy, followed by dostarlimab maintenance. For pMMR, which represent the remaining 80% of patients, checkpoint inhibitors are not approved. As such, the primary treatment option is chemotherapy, followed by watch and wait. Patients whose tumors are both pMMR and TP53 wild type represent 40%-55% of all advanced or recurrent endometrial cancer patients.
As you can see on slide 22, long-term follow-up from the TP53 wild type subgroup from the SIENDO trial, which evaluated selinexor as a maintenance therapy and thus after completion of approximately six months of chemotherapy, shows a median PFS for selinexor of 27.4 months and 5.2 months for placebo, corresponding to a hazard ratio of 0.41. These robust subgroup data demonstrate the potential to provide substantial benefit to a unique and sizable population defined by TP53 status, which directly ties to selinexor's mechanism of action, given that XPO1 inhibition retains TP53 within the nucleus, thus enhancing cell kill. As shown on slide 23, the benefit observed with selinexor in the pMMR subpopulation is even more impressive, with a hazard ratio of 0.32 and a median PFS that was not reached as of our most recent data cutoff.
The preliminary overall survival is encouraging, with a hazard ratio of 0.76 observed in all patients with TP53 wild type and a hazard ratio of 0.57 in the subgroup of patients that are TP53 wild type and pMMR. These efficacy data, coupled with the generally manageable side effect profile, suggest that oral selinexor is uniquely positioned as an optimal maintenance therapy, where convenience, tolerability, and meaningful efficacy are the hallmarks of a maintenance option. In fact, some of our patients are now reaching their fourth year on therapy. I'm excited to present additional follow-up data later this year. On slide 24, you can see the design of our EC-042 pivotal phase III study, which will enroll approximately 220 women whose tumors are TP53 wild type. We look forward to presenting top-line results in the first half of 2025. Turning now to multiple myeloma.
As seen on slide 26, we are expanding our multiple myeloma franchise with the ongoing phase III trial that is evaluating selinexor at the low dose of 40 mg in combination with the well-established backbone therapy of pomalidomide and dexamethasone, post-anti-CD38 antibodies, which will drive earlier use. We are enrolling patients with relapsed refractory multiple myeloma who have received an anti-CD38 antibody as their most recent therapy. As we are seeing positively evolving data with longer median PFS observed with selinexor 40 mg in combination with pomalidomide and dexamethasone, a beneficial outcome for these patients, top-line data are now expected in the first half of 2025. In summary, we have near-term late-stage opportunities supported by compelling data in our rapidly advancing pipeline that will potentially benefit multiple cancer patient populations of high unmet need, building on our approved indications.
With that, I will now hand it over to Sohanya to review our commercial highlights.
Turning now to slide 28 and our commercial highlights for the fourth quarter and full year 2023. In 2023, we achieved $112 million XPOVIO net revenue, meeting our guidance for the year. In the fourth quarter 2023, XPOVIO net revenues were $25 million. During 2023, we achieved total demand growth in the community setting and shifted patient mix into earlier lines, consistent with our strategy. We increased our breadth of use, growing our community prescribing sites of care by approximately 20% year-over-year. The community setting now represents two-thirds of our business and is where the large majority of early-line patients are treated. In Q4 2023, XPOVIO new patient share was approaching 70% in the second to fourth lines, representing double-digit growth year-over-year. This shift in mix of patients continues to drive higher refills as early-line patients tend to stay on therapy longer.
We faced some considerable headwinds in 2023, including increased competition from new entrants in the bispecific class in the later lines, which adversely impacted demand in the academic setting in the second half of 2023. Additionally, higher gross-to-net , driven by increased 340B discounts and Medicaid rebates due to the Inflation Reduction Act, and a significant increase in the free drug or patient assistance program utilization due to closures of multiple myeloma foundations, adversely impacted our revenue. In 2023, PAP contributed to 10% of total demand versus 5% in 2022, resulting in roughly a $6 million impact in 2023. As we turn to 2024, we are working to grow our multiple myeloma business versus last year and are guiding to a U.S. XPOVIO net product revenue range of $100 million-$120 million.
We believe our guidance range reflects a balance of conviction in our near-term growth strategy for XPOVIO while also recognizing the increasingly competitive nature of the myeloma landscape. For XPOVIO, we remain focused on growth in three key areas. First, the community setting. This is where a majority of physicians tend to treat early-line patients and are looking for agents that are effective, manageable, and convenient. We believe that as DARZALEX use expands in the front line, particularly in the community setting, it opens up new opportunities for XPOVIO in the second to fourth lines. This is strengthened by our new data and elevation of selinexor in the NCCN guidelines. Second, early lines of therapy. We will remain focused on further shifting the use of selinexor into early lines of therapy where we see the benefit of increasing duration of therapy. Third, T-cell fitness.
We plan to further build on the evidence around the effectiveness of XPOVIO pre and post-T-cell redirecting therapies, enabling a flexible position for selinexor in the treatment paradigm as a novel mechanism of action. As we look to the future of a multiple myeloma franchise, we believe that as a profitable business generating a 2-to-1 ROI, it will continue to provide a steady inflow of cash to fuel our pipeline and continue to drive confidence and experience in our product at a lower dose as we prepare for future launches, including the potential approval of the all-oral SPD regimen, which could unlock further growth. Our story in multiple myeloma has been one of resilience and steadfastness in a highly competitive and rapidly evolving environment, where the disease remains incurable and XPOVIO continues to be an effective option for many patients.
Finally, our commercial organization is well-established and has developed deep relationships in the community, which represents a key overlapping customer base in both myelofibrosis and endometrial cancer to enable rapid launches in these areas. Now, I would like to turn the call over to Mike to give an update on our financials.
Good morning, everyone, and thank you, Sohanya. Turning to our financials, since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 30. Total revenue for the fourth quarter of 2023 was $33.7 million, similar to total revenue in the fourth quarter of 2022. Total revenue for the full year 2023 was $146 million compared to $157.1 million for the full year 2022. Net product revenue from U.S. commercial sales of XPOVIO for the fourth quarter of 2023 was $25.1 million compared to $31.1 million for the fourth quarter of 2022. Net product revenue from U.S. commercial sales of XPOVIO for the full year 2023 was $112 million compared to $120.4 million for the full year 2022.
The gross-to-net discount for XPOVIO in the fourth quarter of 2023 was 23.5%, and for the full year 2023 was 22%. We expect the gross-to-net discount to be in the 25%-30% range for the full year 2024, and as seen in previous years, it is expected to be at the higher end of the range for Q1. R&D expenses for the fourth quarter of 2023 were $39.4 million compared to $30.9 million for the fourth quarter of 2022, and $138.8 million for the full year 2023 compared to $148.7 million for the full year 2022. The decrease in R&D expenses was primarily attributable to the decrease in personnel costs as a result of the reduction in headcount, in line with the prioritization of our late-stage clinical pipeline and decrease in severance-related expenses.
These decreases were partially offset by an increase in clinical trial and related costs, primarily due to the advancement of our three pivotal phase III studies, which is expected to slightly increase our R&D expenses in 2024. SG&A expenses for the fourth quarter of 2023 were $30.7 million compared to $34.6 million for the fourth quarter of 2022. SG&A expenses for the full year 2023 were $131.9 million compared to $145.4 million for the full year 2022. The decrease in SG&A expenses in 2023 compared to 2022 was due to a decrease in stock-based compensation because of severance-related expenses incurred in 2022. In 2024, we expect our SG&A expenses to slightly decrease as we continue to see the benefits of our cost optimization efforts.
On a non-GAAP basis, which excludes stock-based compensation, our total R&D and SG&A expenses in 2023 were $249.3 million, in line with our guidance for the year. Cash, cash equivalents, restricted cash, and investments as of December 31, 2023, totaled $192.4 million compared to $279.7 million as of December 31, 2022. Based on our current operating plans, we are expecting total revenue of $140 million-$160 million for 2024, consisting of U.S. XPOVIO net product revenue and license, royalty, and milestone revenue expected to be earned from our partners, primarily Menarini and Antengene. We expect U.S. XPOVIO net product revenue of $100 million-$120 million. Our R&D and SG&A expenses to be in the range of $260 million-$280 million for the full year of 2024, including expected stock-based compensation expense of $20 million-$25 million.
And finally, that our existing cash, cash equivalents, and investments, as well as the revenue we expect to generate from XPOVIO net product sales and other license revenues, will be sufficient to fund our planned operations into late 2025. In summary, we continue to be very diligent in allocation of our resources, and looking at our projected 2024 expenses, we see the results of our pipeline prioritization and headcount reductions over the past couple of years. We are rapidly advancing our three phase III trials and driving our commercial performance while keeping overall expense growth minimal. I'll now flip to slide 31 and turn the call over to Richard for some final thoughts. Richard.
Thank you, Mike. As you can see on slide 32, we are excited about our innovation and growth strategy with our phase III clinical trials in multiple myeloma, endometrial cancer, and myelofibrosis, each of which would be transformative for patients and our organization. As I mentioned at the start of the call, we believe the largest opportunities for selinexor are yet to come. With data expected from these three phase III trials next year, it's going to be an incredibly exciting time for our organization. We are focused on delivering on our next phase of growth as our people continue to strive each day for patients with high unmet needs, working to generate value for patients and shareholders. Thank you again for joining us today, and I would now like to ask the operator to open the call up to the Q&A portion of today's call. Operator.
Thank you. And ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the number one on your telephone keypad. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number two. And if you're using a speakerphone, please flip the handset before pressing any keys. One moment, please, for your first question. And your first question comes from the line of Peter Lawson from Barclays. Your line is open.
Great. Thanks so much. Maybe a question for Mike or Sohanya, just around is there any way to kind of quantify the community versus academic setting growth in 2023 and kind of what you think that looks like exiting the year and into 2024?
Yeah, thanks, Peter, for the question. When you look overall, I think, as Sohanya talked to during our prepared comments, you really need to differentiate the environment between the community setting and the academic setting. I'll turn to Sohanya to kind of elaborate on that, looking at 2023 into 2024.
Thanks, Peter, for the question. In 2023, as we take a step back, despite the rapid evolution in the competitive landscape, we did achieve total demand growth year-over-year in 2023 in the community setting. This is an area of hyper-focus for us and a clear growth driver for us in 2024. Another key accomplishment in the community for us in 2023 is we really broadened our sites of care. So we now have a broad base of prescribers. We increased our prescriber base by about 20% year-over-year. That is an area where we want to drive depth in the community in 2024. Again, this is the largest contributor of our business. It's about two-thirds of our business. Switching to the academic setting, that contributes to about a third of our business, and this is where we see a rapid evolution of the competitive landscape.
So last year, we were really in the eye of the storm, especially in the second half of the year, where we saw downward demand pressure as a result of the uptake of the bispecific class. Two of the three bispecifics launched in the second half of last year. Now, as we move into 2024, we do see a couple of new dynamics come into play: potential approval of a fourth bispecific, potential shifts of CAR-Ts into early lines. However, in terms of defending our business in the academic setting, it's really around enabling a flexible position for selinexor as a novel mechanism that's easily combinable and supported by our T-cell fitness data. So that allows us to really play in the potential pre and post-T-cell therapy space in the academic setting.
Perfect. Thank you. Then just the impact of BCMA therapies, do you think that kind of continues through 2024, or have you seen kind of the major shift already kind of happened?
Yeah. So the bispecifics, as I touched on, really posed a significant competitive threat in the academic setting, particularly in the second half of last year. As I mentioned, two of the three launched in the second half. Now, we haven't seen that uptake in the community. We think that's going to be minimal impact in the near term in the community. But in the academic setting, we definitely saw impact. Now, in real world, we are seeing that these patients are on bispecifics for about eight-nine months. Many are progressing. So it's not a curable option. As we think about the role of selinexor relative to the bispecifics, we have published data on positive outcomes post-BCMA failures. So that really allows us to position ourselves after a bispecific and, in many cases, pre-bispecifics as well.
Great. Thank you so much. I'll jump back into the queue.
Thanks, Peter.
Thank you. Your next question comes from the line of Maury Raycroft from Jefferies. Your line is open.
Hi, good morning, and thanks for taking my questions. I was going to ask one or two on myelofibrosis. Wondering what your thoughts are on the recent acquisition of MorphoSys and what read-throughs there would be to Karyopharm based on how the regulatory process could play out, particularly on the TSS endpoint, which was their key secondary but is your co-primary endpoint. And could you potentially have further conversations with FDA prior to filing and/or changing the study design if need be?
Thanks, Maury. I'll take the first part of that, and then I'll turn it over to Reshma to take the second part of that. I think when you look at the Novartis and MorphoSys acquisition, I think it really validates the high unmet need in the myelofibrosis space and really talks to the value of the opportunity in myelofibrosis. So I think that's a strong validation of the value and the unmet need in myelofibrosis. And I'll turn to Reshma to talk about what we're looking at in terms of the evolution. And I think we're really in a strong opportunity to watch the evolution of the space as it moves forward.
Yeah, exactly. And thank you for the question, Maury. I think what we presented today really just outlines the strength that we have across the entire profile of selinexor, ruxolitinib, specifically the optimal spleen volume reduction, the symptom improvement, right, not only from a TSS-50 perspective but also now absolute TSS-50. We further looked at individual domains, seeing maximal effect across each of the individual domains too. And all of that is, of course, underscored by the cytokine data. So really a wealth and growing sort of dataset around that symptom score that really suggests that we can maximize benefit across both of those endpoints. Let's not forget disease modification and then, of course, improvement and stabilization of the cytopenia. So again, really just emphasizing that we have the totality profile that is going to be optimal for this JAK-naïve patient population.
We're very encouraged, and we're very confident that when we look at symptoms in our phase III, it is going to show meaningful benefit compared to selinexor alone. As Richard mentioned, I think we've got the best opportunity, right? We have an ongoing phase III. It's currently enrolling. We do know that the environment is evolving, both from a physician perspective but also from an FDA perspective. We're going to capitalize on that. So if there's an opportunity to evolve the endpoints, we have an opportunity to then, of course, incorporate those into our study prior to the database log.
Okay. That's helpful. And maybe one other question. You plan to report the preliminary results from the monotherapy phase II in JAK-naïve myelofibrosis with moderate thrombocytopenia in the second half of this year. Can you talk more about what the strategy is for that study? Is this for potential standalone monotherapy approval path or more for supplementing the combination filing in Lighthouse?
Yeah. Great question. So one of the unique aspects of selinexor is that when we look at preclinical data, obviously clinical data from our relapsed refractory myelofibrosis study, which is the essential study, and then, of course, the subgroup data from our phase I, selinexor plus ruxolitinib, it all points to very intriguing monotherapy activity. Again, this is unique. When you look at other mechanisms of action, whether it's a BET inhibitor or a BCL2 inhibitor, those agents, by and large, do not have that critical monotherapy activity. It's key that physicians ultimately have that flexibility in that dosing. We want to use this phase II study to further investigate this monotherapy activity in this high unmet patient population. We'll have an opportunity to read out some data later this year and really be able to identify whether that activity is meaningful, again, in that high unmet need patient population.
We're really looking at this as a proof of concept study. Potentially, we can expand it, potentially get some NCCN, but right now, it's really to double down and better test this hypothesis that we have with selinexor, again, in this JAK-naïve population.
Got it. Okay. Thanks for taking my questions.
Thanks, Maury.
Your next question comes from the line of Jonathan Chang from Leerink Partners. Your line is open.
Hi, guys. Thanks for taking my questions. First question, can you speak to the enrollment experience of the phase III SPd triplet study in multiple myeloma? And then second question, can you talk about how you're thinking about your cash position and runway and the converts due to mature in October 2025? Thank you.
Yeah, thanks, Jonathan. For the first part of that, I'll turn to Reshma, and then I'll let Mike touch on the second part of that.
Yeah. Thanks, Jonathan, for the question. So the enrollment is going well with that SPD trial. It's an all-oral. As Sohanya mentioned, SPD really represents the only all-oral therapy. Obviously, it has some unique data, pre and post-T-cell therapies, which in this evolving environment is going to be a key attribute for this combination. There's a lot of interest in this study, both in the U.S. as well as the E.U. So we're driving towards enrollment and look forward to announcing completion of the enrollment later this year.
Thanks. On the second question, yes, we finished 2023 with $192 million in cash. We burned approximately $88 million in 2023, which gives us a cash runway with what we're planning for XPOVIO net revenues here in the U.S. as well as partnership revenues offset by spend over the next couple of years into late 2025. As far as the convert goes, the convert is due in October 2025, so it certainly gives us some time. It's very closely held with the top five holders owning greater than 85% of the bonds. So we'll certainly be opportunistic in evaluating our options around the convert.
Got it. Thanks for taking my questions.
Thanks, Jonathan.
Your next question comes from the line of Colleen Kusy from Baird. Your line is open.
Great. Good morning. Thanks for taking our questions. Any comments you can offer on Q1 so far? I think you had mentioned last year that the third-party reimbursement foundations wouldn't be as impactful this year with IRA coming online. So can you just anything notable with the IRA rollout so far this year and any seasonality you're seeing yet in Q1?
Yeah. Thanks, Colleen. I mean, I'll just talk about that at a high level. We just don't provide comments kind of interquarter, so we'll update on Q1. But as we're progressing in Q1 here, we feel very good about being able to deliver our full-year guidance.
Great. With some exciting label expansion opportunities ahead, can you just make some comments, remind us on your IP position for selinexor? When does the composition of matter expire, and how long do you think you could be protected beyond that?
Yeah. Thanks, Colleen. As you know, I think we've had some really positive evolution with regards to our IP position. And obviously, we work very hard to make sure we protect our valuable inventions here in the U.S. and globally. Last year, in Q3, we were able to achieve kind of almost one year, 342 days of extension to our composition of matter patent. So that takes us to July of 2033. And then in Q4 of last year, actually, we were able to really work with the patent office and enable to enhance our patents with regard to the polymorphic form of selinexor. And the newly issued patents expire in August of 2035. And we really believe that these polymorphic form use our API is differentiated from other forms and really offers clear novel benefits.
For us, a long runway in front of us with regards to patent protection.
Great. That's helpful. Thanks for taking our questions.
Thanks, Colleen.
And your next question comes from the line of Brian Abrahams from RBC Capital Markets. Your line is open.
Hi. This is Joel for Brian. Thanks for taking our question. Question on the new monotherapy study in MF. I believe you're allowing add-on therapies in the study. Can you talk about how many patients are expected to go on add-on therapies over the course of the study and also any synergistic benefits you may expect to see with pacritinib and momelotinib? Thank you.
Yeah. Thanks, Joel. Sorry. Go ahead, Reshma.
I jumped the gun. I apologize. It's a great question, Joe. So the monotherapy study, as you mentioned correctly, does allow the option to add on different therapies as early as week 12. Now, with that said, if the patient is deriving benefit both from an SVR and TSS perspective, we really want them to continue on selinexor monotherapy. And as I mentioned earlier, given all of the preclinical and clinical data, we really do feel confident that selinexor monotherapy is going to drive that benefit across those two endpoints, which really suggests that a very small proportion, if that, is likely going to need an add-on therapy in the form of momelotinib, pacritinib, or ruxolitinib. So we'll wait to see as the study continues to roll out and as we see additional patients, we see patients being enrolled on the study.
But again, I think it is going to be a small proportion of patients.
Thank you so much.
Thanks, Joel.
Your next question comes from the line of Steve Bursey from H.C. Wainwright. Your line is open.
Hey. This is Steve on for Ed. So you were saying there was more of a shift into earlier lines of therapy and the increased duration of patient-on-drug. Can you put any numbers to that? And is there a difference between the second-line to fourth-line and penta-refractory patients?
Yeah. Thanks, Steve. I mean, I'll just at a high level, as we talked about, looking at the numbers in detail is very difficult, and it's more directional. And I'll turn to Sohanya to talk about that impact as we're looking at the ongoing shift into the earlier lines, which, again, is right in line with our strategy and where we're going to continue to focus. Sohanya?
Yeah. So we continue to see an upward trend in our duration of therapy, and that is really primarily driven by the earlier line patients who do tend to stay on therapy much longer than the later line patients. We are also seeing the duration increase because our physicians are getting more comfortable in managing these patients with the right supportive care at the lower dose and so on. So again, won't disclose the specifics of the duration, but we see an upward trend, and we expect to continue to see a positive shift in our duration as we move forward.
Okay. Thanks for taking our question.
Thanks, Steve.
Thank you. Our Q&A session has now ended. I would like to turn it back to Richard Paulson, President and Chief Executive Officer of Karyopharm. For closing comments.
Thank you, Ludi. And once again, thank you, everyone, for joining us today. I think, as I mentioned before, we're very excited about our innovation and growth strategy. Our phase III clinical trials are moving forward rapidly, and we believe the largest opportunities for selinexor are yet to come as we focus on delivering this next phase of growth. And as we mentioned, everybody inside Karyopharm is focused on striving each day for patients' high unmet needs and working to generate value for our patients and shareholders. So once again, thank you for joining us today.
Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.