Karyopharm Therapeutics Inc. (NASDAQ:KPTI) Q4 2023 Earnings Call Transcript

Karyopharm Therapeutics Inc. (NASDAQ:KPTI) Q4 2023 Earnings Call Transcript February 29, 2024

Karyopharm Therapeutics Inc. misses on earnings expectations. Reported EPS is $-0.36 EPS, expectations were $-0.29. FDS isn’t one of the 30 most popular stocks among hedge funds at the end of the third quarter (see the details here).

Operator: 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 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.

Elhan Webb: Thank you, Ludy 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, are available on our website. For today’s call as seen on slide 2, 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 will make today constitute forward-looking statements, FLS for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995 as outlined on slide 3.

Actual results may differ materially from those indicated by 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 this FLS at some point in the future, we specifically disclaim any obligation to do so even if our views change. Therefore, you should not rely on these FLS as representing our views as of any later date. I will now turn the call over to Richard. Please turn to slide 4.

Richard Paulson: 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 readout 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 advanced disease stage pipeline, address patients’ unmet needs. And if approved, rapidly expand selinexor is used 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 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 a financial strength to deliver on key data readouts from our three Phase three 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 to $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 are focused on both near term and long term growth. Importantly, our existing commercial infrastructure is profitable to date and provides us with the capability to support their 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 US alone. 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 myelofibrosis, we are very encouraged by the comprehensive profile including tolerability, spleen volume reduction, symptom improvement as measured by TSS50 and a long-term durability that we saw in our Phase 1 data of selinexor plus ruxolitinib in JAKi-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 to 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 it used to earlier lines of treatment.

We look forward to the results from our Phase 3 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 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?

Reshma Rangwala: Thank you, Richard and good morning, everyone. As Richard mentioned on slide 9, we have a very promising late-stage pipeline with selinexor in three Phase 3 studies, all of which incorporates 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 JAKi-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. 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 of ruxolitinib in JAK inhibitor naive patients, which showed an SVR35 at 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 TSS50 and absolute TSS showed very meaningful improvements at week 24. 58% of the intent-to-treat and 78% of the efficacy evaluable achieved the TSS50 response.

For absolute TSS, an average 18.5 point improvement was observed in the efficacy evaluable population at the same time points, compare this to historical ruxolitinib data, where TSS50 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, TSS50 and individual domain improvements are corroborated by cytokine data, which showed that the pro-inflammatory cytokine which lead to myelofibrosis symptom development show rapid, deep and sustained reductions relative to baseline.

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 funded the durability data from the selinexor/ruxolitinib combinations very important for patients as of the most recent data cut off none of the week 24 SVR35 responders dose that selinexor 60 milligrams had observed radiographic progression and none of the week 24 TSS50 responders had observed symptom progression. 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 TSS50 together we see that 50% of patients experienced both of these responses at week 24% and 75% experienced both SVR35 and TSS50 response at any time.

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 in 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 naive myelofibrosis patients. In fact one of the most prominent opinion leaders and the principal investigator of the selinexor plus ruxolitinib Phase 3 study Dr. John Mascarenhas 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.

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 360 JAK naive 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 just sarilumab in combination with chemotherapy followed by the sarilumab 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 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 should the median PFS for selinexor 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 P53 status which directly ties to selinexor as a 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 cutoff. 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 PMR. These efficacy data coupled with a generally manageable side effect profile suggests that oral selinexor is uniquely positioned as an optimal maintenance therapy or convenience, tolerability and meaningful efficacy are the hallmarks of the 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 3 study, which will enroll approximately 220 women whose tumors or 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 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. 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 milligrams 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.

Sohanya Cheng: 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 earlier line patients are treated. In Q4 2023, XPOVIO new patient share was approaching 70% in the second to fourth line 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 2023. Additionally, higher gross to net, driven by increased 340B discounts and Medicaid rebates due to the inflation reduction at and a significant increase in the free drug of 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 US XPOVIO net product revenue range of $100 million to $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 majority of physicians tend to treat earlier 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, 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. 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 multiple myeloma franchise, we believe that as a profitable business, generating a 2:1 ROI, it will continue to provide a steady inflow of cash to fill our pipeline and continue to drive confidence an 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 said fasteners in a highly competitive and rapidly evolving environment, whether 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.

Michael Mason: 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 US 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 US commercial sales of XPOVIO for the full year 2022 was $112 million compared to $120.4 million for the full year of 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% 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&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 of 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 3 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 were 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 continued 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 for $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 31st 2022. Based on our current operating plans, we are expecting total revenue of $140 million to $160 million for 2024 consisting of US XPOVIO net product revenue and license, royalty and milestone revenue expected to be earned from our partners primarily Menarini and Entergy. We expect US XPOVIO net product revenue of $100 million to $120 million. R&D and SG&A expenses to be in the range of $260 million to $280 million for the full year of 2024 including expected stock-based compensation expense of $20 million to $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 3 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?

Richard Paulson: 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 three Phase 3 trials next year is 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?

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Q&A Session

Operator: Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. [Operator Instructions] And your first question comes from the line of Peter Lawson from Barclays. Your line is open.

Peter Lawson: 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 that you think that looks like and exiting the year and into 2024?

Richard Paulson: Yes. Thanks Peter for the question. And when I look overall I think Sohanaya talked to during our prepared comments. We really need to differentiate the environment between the community setting and the academic setting. And I’ll turn to Sohanya to elaborate on that looking at 2023 into 2024.

Sohanya Cheng: Thank 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-on-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 one-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 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.

Peter Lawson: 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?

Sohanya Cheng -: Yeah. So the bispecifics as I touched on, it 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 that’s going to be a minimal impact in the near term in the community. But in the academic setting, we definitely saw an impact. Now in real world, we are seeing that these patients are on bispecifics for about eight to 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 bispecific and in many cases pre bispecifics as well.

Peter Lawson: Thank you so much. I’ll jump back in queue.

Richard Paulson: Thanks, Peter.

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

Maury Raycroft: Hi. Good morning, and thank you for taking my questions. I was going to ask one or two in myelofibrosis. I’m 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 change the study design it may be.

Richard Paulson: Thanks, Moray. 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, 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?

Reshma Rangwala: Yeah, exactly. And thank you for the question, Maury. I think what we presented today really Jeff 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 the TSS. 50 perspective, but also now absolute TSS. 50. We further looked at individual domains seeing maximal effect across each of the individual domains to. And all of that is of course underscored by the cytokine data. So really a wealth and growing unit sort of data set around that symptom score that really suggests that we can maximize the benefit across both of those endpoints. And let’s not forget, disease modification and then of course improvement and stabilization of the cytopenias.

So again, really just emphasizing that we have the totality profile that is going to be optimal for this Jack 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? We have an ongoing Phase three. 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 that database lock.