Karyopharm Therapeutics Q4 2023 Earnings Call Transcript

Quartr
Provided by Quartr
February 29, 2024

There are 9 speakers on the call.

Operator

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 Curuform Therapeutics 4th 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.

Operator

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

Speaker 1

Thank you, Luthie, 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 Q4 and full year 2023. This release along with a slide presentation that we will reference during our call today are available on our website. For today's call, as seen on Slide 2, I'm joined by Richard, Reshma, Soania and Mike, who will provide an update on our results for the Q4 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 as follows for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995 as outlined on Slide 3.

Speaker 1

Actual results may differ materially from those indicated by these FLX as a result of various important factors, including those discussed in the Risk Factors section of our most recent Form 10Q or 10 ks, which are on file with the SEC and in other filings that we may make with the SEC in the future. Any FLS represents 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 now rely on these FLS as

Speaker 2

Good morning. Thank you, Alhan, 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 5, over the past few years, we have been intensely focused on positioning ourselves for our next stage of growth with 3 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.

Speaker 2

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 multiple myeloma franchise anchored on our commercial drug, EXPOVIO, which is approved in over 40 countries, generating brand profitability and growing experience with physicians. Through ongoing disciplined expense management, we have In 2023, we delivered total revenues of $146,000,000 meeting our guidance for full year and in 2024 we expect to generate $140,000,000 to $160,000,000 total revenues. This range reflects the highly competitive nature of the multiple myeloma market with important new entrants in the second half of twenty twenty three and more anticipated this year, which we are mindful of especially when setting expectations for our financial performance this year.

Speaker 2

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 $2,000,000,000 of peak annual revenues in the U. S. Alone.

Speaker 2

And turning now to Slide 6, let's review some key accomplishments from our core programs in 2023, which strengthen our confidence in our ongoing Phase 3 trials. In myofibrosis, we are very encouraged by the comprehensive profile, including tolerability, spleen volume reduction, symptom improvement as measured by TSS-fifty and the long term durability that we saw in our Phase 1 data of selinexor plus ruxolitinib in JAK naive 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 at 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 EXPOVIO in the community setting and shifted its use to earlier lines of treatment.

Speaker 2

We look forward to the results from our Phase 3 trial evaluating selinexor at the well dose of 40 milligrams in combination with the well established backbone therapy of pomalidomide and dexamethasone post anti CD38 antibodies. Turning now to Slide 7, as we work to create new standards of care, we expect each of our ongoing Phase 3 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 8, I would now like to turn the call over to Reshma to expand further on our clinical pipeline progress. Reshma?

Speaker 3

Thank you, Richard, and good morning, everyone. As Richard mentioned on Slide 9, we have a very promising late stage pipeline with selinexor in 3 Phase 3 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 naive 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.

Speaker 3

Xpl1 inhibition is a fundamental mechanism in myelofibrosis, given that it targets both JAK and non JAK pathways, underscoring selinexor's additive is 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 inhibitor naive patients, which showed an SVR35 of 79% at week 24 in the intent to treat population. Importantly, amongst the evaluable patients, 100% achieved in SVR35 at any time. On Slide 13, both TSS 50 and absolute TSS showed very meaningful improvements at week 24.

Speaker 3

58% of the intent to treat and 78% of the efficacy evaluable achieved the TSS 50 response. For absolute TSS, an average 18.5 point improvement was observed in the efficacy evaluable population at the same time point. Compare these to historical ruxolitinib data where TSS 50 was observed in 42% to 46% of ruxolitinib treated patients and the average TSS improvement was 11 to 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-fifty 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.

Speaker 3

Taken together, 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 3 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 cut off, 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 SBR35 and TSS50 response at any time.

Speaker 3

On Slide 17, we see that in addition to the cytokine data, we also observed 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 JAK naive myelofibrosis patients. In fact, one of the most prominent opinion leaders and the principal investigator of the selinexor plus ruxolitinib Phase 3 study, Doctor. John Mascarenas noted that the combination is tolerable and that the spleen and symptom data observed to date from the Phase 1 study may significantly improve these outcomes in first line myelofibrosis.

Speaker 3

As the body of data grow and positively evolve, we maintain a high level of confidence in the ongoing Phase 3 study shown on Slide 19, which is evaluating the combination of selinexor 60 milligrams with ruxolitinib versus ruxolitinib alone in 306 JAK naive myelofibrosis patients. We are on track to report top line results in the second half of twenty twenty five. Turning now to endometrial cancer. As seen on Slide 21, there is a paradigm shift underway for treatment of women with advanced and 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.

Speaker 3

Today, for DMMR patients who represent approximately 20% of advanced recurrent endometrial cancer, the new FDA approved standard is dastarlimab in combination with chemotherapy, followed by dastarlimab 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 p53 wild type represent 40% to 55% of all advanced recurrent endometrial cancer patients. As you can see on Slide 22, long term follow-up from the TP53 wild type subgroup from the SIENDRA trial, which evaluated selinexor as a maintenance therapy and thus after completion of approximately 6 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.

Speaker 3

These robust subgroup data demonstrate the potential to provide substantial benefit to a unique and sizable population defined by p53 status, which directly ties to selinexor's mechanism of action given that XPO1 inhibition retains p53 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 cut off. The preliminary overall survival is encouraging with the hazard ratio of 0.76 observed in all patients with TP53 wild type and hazard ratio of 0.57 in the subgroup of patients that are p53 wild type and PMMR. These efficacy data coupled with the generally manageable side effect profile suggests that oral selinexor is uniquely positioned as an optimal maintenance therapy where convenience, tolerability and meaningful efficacy are the hallmarks of the maintenance option. In fact, some of our patients are now reaching their 4th year on therapy.

Speaker 3

I'm excited to present additional follow-up data later this year. On Slide 24, you can see the design of our EC-forty two pivotal Phase 3 study, which will enroll approximately 220 women whose tumors are PP53 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 3 trial that is evaluating selinexor at the low dose of 40 milligrams in combination with the well established backbone therapy of pomalidomide and dexamethasone post anti CD38 antibodies, which will drive earlier use.

Speaker 3

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 CSS observed with selinexor 40 milligrams in combination with pomalidomide and dexamethasone, a beneficial outcome for these patients. Top line data are now expected in the first half of twenty twenty five. 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 Solania to review our commercial highlights.

Speaker 3

Turning now to Slide 28 and our commercial highlights for the Q4 and full year 2023. In 2023, we achieved $112,000,000 Exovio net revenue meeting our guidance for the year. In the Q4 2023, exovio net revenues were 25,000,000 dollars 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 2 thirds of our business and is where the large majority of early aligned patients are treated.

Speaker 3

In Q4 2023, EXPOVIO 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 earlier 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 twenty 23. 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 $6,000,000 impact in 2023.

Speaker 3

As we turn to 2024, we are working to grow our multiple myeloma business versus last year and are guiding to a U. S. Exovio net product revenue range of $100,000,000 to 120,000,000 dollars We believe our guidance range reflects a balance of conviction in our near term growth strategy for XBOVIO, while also recognizing the increasingly competitive nature of the myeloma landscape. For Xpovio, we remain focused on growth in 3 key areas. 1st, the community setting.

Speaker 3

This is where majority of physicians tend to treat early aligned patients and are looking for agents that are effective, manageable and convenient. We believe that as DARZALEX use expands in the frontline, particularly in the community setting, it opens up new opportunities for XPOVIO in the 2nd or 4th lines. This is strengthened by our new data and elevation of selinexor in the NCCN guidelines. 2nd, earlier lines of therapy. We will remain focused on further shifting the use of selinexor into earlier lines of therapy where we see the benefit of increasing duration of therapy.

Speaker 3

3rd, T cell fitness. We plan to further build on the evidence around the effectiveness of exposure 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 our multiple myeloma franchise, we believe that as a profitable business, generating a 2:one 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 EXPOVIO 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.

Speaker 3

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

Speaker 2

Good morning, everyone, and thank you, Suhania. 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 Q4 of 2023 was $33,700,000 similar to total revenue in the Q4 of 2022. Total revenue for the full year 2023 was $146,000,000 compared to $157,100,000 for the full year 2022. Net product revenue from U.

Speaker 2

S. Commercial sales of XPOVIO for the Q4 of 2023 was $25,100,000 compared to $31,100,000 for the Q4 of 2022. Net product revenue from U. S. Commercial sales of XPOVIO for the full year 2022 was $112,000,000 compared to $120,400,000 for the full year of 2022.

Speaker 2

The gross to net discount for XPOVIO in the Q4 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% to 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 and D expenses for the Q4 of 2023 were $39,400,000 compared to $30,900,000 for the Q4 of 2022 and $138,800,000 for the full year of 2023 compared to $148,700,000 for the full year 2022. The decrease in R and 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 3 pivotal Phase III studies, which is expected to slightly increase our R and D expenses in 2024.

Speaker 2

SG and A expenses for the Q4 of 2023 were $30,700,000 compared to $34,600,000 for the Q4 of 2022. SG and A expenses for the full year of 2023 were $131,900,000 compared to $145,400,000 for the full year 2022. The decrease in SG and A expenses in 2023 compared to 2022 were due to a decrease in stock based compensation because of severance related expenses incurred in 2022. In 2024, we expect our SG and A expenses to slightly decrease as we continue to seek the benefits of our cost optimization efforts. On a non GAAP basis, which excludes stock based compensation, our total R and D and SG and A expenses in 2023 were $249,300,000 in line with our guidance for the year.

Speaker 2

Cash, cash equivalents, restricted cash and investments as of December 31, 20 Based on our current operating plans, we are expecting total revenue of $140,000,000 to $160,000,000 for 20.24 consisting of U. S. Exfoliovio net product revenue and license, royalty and milestone revenue expected to be earned from our partners, primarily Menarini and Antigene. We expect U. S.

Speaker 2

Exfoliovo net product revenue of $100,000,000 to $120,000,000 R and D and SG and A expenses to be in the range of $260,000,000 to $280,000,000 for the full year of 2024, including expected stock based compensation expense of 20 $1,000,000 to $25,000,000 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 3 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?

Speaker 2

Thank you, Mike. As you can see on Slide 32, we are excited about our innovation and growth strategy with our Phase 3 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 3 Phase 3 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.

Speaker 2

Thank you again for joining us today. And I would now like to ask the operator to open the call up to the Q and A portion of today's call. Operator?

Operator

Thank you. You. And your first question comes from the line of Peter Lawson from Barclays. Your line is open.

Speaker 4

Great. Thanks so much. Maybe a question for Mike or Sonia, just around there's any way to kind of quantify the community versus academic setting growth in 'twenty three and kind of what that you think that looks like exiting the year and into 2024?

Speaker 2

Yes. Thanks, Peter, for the question. I think when you look overall, I think as Sonja talked to during our prepared comments, you really need to differentiate the environment between the community setting and the academic setting. And I'll turn to Sohane to elaborate on that looking at 2023 into 2024.

Speaker 3

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 20 23 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.

Speaker 3

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 2 thirds of our business. Switching to the academic setting that contributes to about a third of our business, and this is where we see rapid evolution of the competitive landscape.

Speaker 3

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. 2 of the 3 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 4th bispecific potential shifts of CAR Ts into earlier 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.

Speaker 4

Perfect. Thank you. And then just the impact of BCMA therapies, do you think that kind of continues through 2024? Have you seen kind of the major shift already kind of happened?

Speaker 3

Yes. 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, 2 of the 3 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.

Speaker 3

But in the academic setting, we definitely saw impact. Now in real world, we are seeing that these patients are on bispecifics for about 8 to 9 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.

Speaker 3

So that really allows us to position ourselves after a bispecific and in many cases pre bispecifics as well.

Speaker 4

Thank you so much. I'll jump back into the queue.

Speaker 2

Thanks, Peter.

Operator

Thank you. And your next question comes from the line of Maury Raycroft from Jefferies. Your line is open.

Speaker 5

Hi, good morning and thanks for taking my questions. I was going to ask 1 or 2 on myelofibrosis. Wondering what your thoughts are on the recent acquisition of MorphoSys and what read throughs there would be to carry a farm 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 change the study design, if need be?

Speaker 2

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, it really validates the high unmet need in the myelofibrosis space and really talks to the value of the opportunity of 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.

Speaker 3

Yes, 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-fifty perspective, but also now absolute TSS-fifty. 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.

Speaker 3

So really a wealth and growing sort of data set 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 naive patient population. We're very encouraged and we're very confident that when we look at symptoms in our Phase 3, it is going to show meaningful benefit compared to selinexor alone. As Richard mentioned, I think we've got the best opportunity, right?

Speaker 3

We have an ongoing Phase 3. It's currently enrolling. We do know that the environment is evolving, both from a physician perspective, but also from an FDA perspective. And 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 lock.

Speaker 5

Okay. That's helpful. And maybe one other question. You plan to report the preliminary results from the monotherapy Phase 2 inject naive myelofibrosis with moderate thrombocytopenia in the second half of this year. Can you talk more about what the strategy is for that study?

Speaker 5

Is this for potential standalone monotherapy approval path or more for supplementing the combination filing in label?

Speaker 3

Yes. Great question. So one of the unique aspects of selinexor is that when we look at preclinical data, obviously, clinical data from a relapsed refractory myelofibrosis study, which is the essential study. And then of course the subgroup data from our Phase 1 selinexor plus ruxolitinib, it all points to very intriguing monotherapy activity. Again, this is unique.

Speaker 3

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 2 study to further investigate this monotherapy activity in this high Aetna 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 net need patient population. We're really looking at this as a proof of concept study.

Speaker 3

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 naive population.

Speaker 5

Got it. Okay. Thanks for taking my questions.

Speaker 2

Thanks, Marty.

Operator

And your next question comes from the line of Jonathan Chang from Leerink Partners. Your line is open.

Speaker 6

Hi, guys. Thanks for taking my questions. First question, can you speak to the enrollment experience of the Phase 3 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.

Speaker 2

Yes. 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.

Speaker 3

Yes. Thanks, Jonathan, for the question. So, the enrollment is going well with that SPD trial. It's an all oral, as Silhania mentioned. STD really represents the only all oral therapy.

Speaker 3

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 EU. So we're driving towards enrollment and look forward to announcing completion of the enrollment later this year.

Speaker 2

Thanks. And on the second question, yes, we finished 2023 with $192,000,000 in cash. We burned approximately $88,000,000 in 2023, which gives us a cash runway with our what we're planning for exovio net revenue here in the U. S. As well as partnership revenues offset by spend over the next couple of years into late 2025.

Speaker 2

And 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 5 holders owning greater than 85 percent of the bonds. So we'll certainly be opportunistic in evaluating our options around the convert.

Speaker 6

Got it. Thanks for taking my questions.

Speaker 2

Thanks, Jonathan.

Operator

And your next question comes from the line of Colleen Kosey from Baird. Your line is open.

Speaker 7

Great. Good morning. Thanks for taking our questions. Any comments you can offer on 1Q so far? I think you had mentioned last year that the 3rd party reimbursement foundations wouldn't be as impactful this year with IRA coming online.

Speaker 7

So can you just anything notable with the IRA rollout so far this year and any seasonality you're seeing yet in 1Q?

Speaker 2

Yes. Thanks, Colleen. I mean, I'll just talk about that at a high level. We just don't provide comments kind of inter quarter. So we'll update on Q1.

Speaker 2

But as we're progressing in Q1 here, we feel very good about being able to deliver our full year guidance.

Speaker 7

Great. And then 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 matter expire and how long do you think you could be protected beyond that?

Speaker 2

Yes. Thanks, Colleen. As 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.

Speaker 2

And globally. Last year in Q3, we were able to achieve kind of almost 1 year, 342 days of extension to our composition of matter patent. So that takes us to July of 2,033. And then in Q4 of last year, actually we were able to really work with 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 2,035. And we really believe that these polymorphic form used our API differentiated from other forms and really offers clear So for us a long runway in front of us with regards to patent protection.

Speaker 7

Great. That's helpful. Thanks for taking our questions.

Speaker 2

Thanks, Collyn.

Operator

And your next question comes from the line of Brian Abrahams from RBC Capital Markets. Your line is open.

Speaker 6

Hi, this is Joe on 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?

Speaker 6

And also any synergistic benefits you may expect to see with pecretinib and momelitinib? Thank you.

Speaker 2

Yes. Thanks, Joe. I think when I'm sorry. Go ahead, Reshma.

Speaker 3

I jumped the gun. I apologize. It's a great question, Joe. So the monotherapy study, as you mentioned correctly, does allow the option 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.

Speaker 3

And as I mentioned earlier, given all of the pre clinical 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 momelatinib, picritinib 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.

Speaker 7

Thanks so much.

Speaker 2

Thanks, Joe.

Operator

And your next question comes from the line of Steve Birche from H. C. Wainwright. Your line is open.

Speaker 8

Hey, this is Steve on for Ed. So you were saying there was a shift, more of a shift into earlier lines of therapy in the increased duration of patient on drug. Can you put any numbers to that? And is there a difference between the 2nd line to 4th line and penorefractory patients?

Speaker 2

Yes. Thanks, Steve. I mean, I'll just add a high level, as you talked to that, looking at the numbers in detail is very difficult and it's more directional. And I'll turn to Sonja 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 then where we're going to continue to focus. Sonja?

Speaker 3

Yes. So we continue to see an upward trend in our duration of therapy and that is really primarily driven by the early aligned 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, we 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.

Speaker 8

Okay. Thanks for taking our questions.

Speaker 2

Thanks, Steve.

Operator

Thank you. Our Q and A session has now ended. I would like to turn it back to Richard Paulson, President and Chief Executive Officer of CaioForm for closing comments.

Speaker 2

Thank you, Udi. 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 3 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.

Speaker 2

So once again, thank you for joining us today.

Operator

Thank you. And ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

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Earnings Conference Call
Karyopharm Therapeutics Q4 2023
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