Karyopharm Therapeutics Inc. (NASDAQ:KPTI) Q3 2023 Earnings Call Transcript

Karyopharm Therapeutics Inc. (NASDAQ:KPTI) Q3 2023 Earnings Call Transcript November 2, 2023

Karyopharm Therapeutics Inc. misses on earnings expectations. Reported EPS is $-0.3 EPS, expectations were $-0.28.

Operator: Good morning. My name is Guru and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics Third Quarter 2023 Financial Results Conference Call. [Operator Instructions] I would now like to turn the call over to Elhan Webb, Senior Vice President of Investor Relations.

Elhan Webb: Thank you. And thank you all for joining us on today’s conference call to discuss Karyopharm’s third quarter 2023 financial results and recent company progress. We issued a press release this morning detailing our financial results for the third quarter 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 am joined by Richard, Reshma, Sohanya and Mike, who will provide an update on our results for the third quarter and recent clinical development. Before we begin our formal comments, I will remind you that various remarks we will make today constitute forward-looking statements, FLS for the 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, which is 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 Slide over to Richard. Please turn to Slide 4.

Richard Paulson: Thank you, Elhan. Good morning, everyone and thank you for joining Karyopharm’s 2023 earnings call. Turning to Slide five, we are strongly positioned for our next stage of growth driven by our focused and rapidly advancing mid and late-stage pipeline of innovative first in class, oral selective inhibitors and nuclear export, their target XPOVIO1, as well as a strong commercial organization that continues to positively impact the lives of multiple myeloma patients every day. Our U.S. and global commercial presence are on track to deliver $145 million to $160 million of annual total revenues in 2023. And provides us with the capabilities needed to launch in new indications. If approved. Following the outcome of our three pivotal Phase 3 clinical trials.

We have the opportunity to significantly improve standard of care for patients across these indications. And we continue to generate compelling data, including impressive durability data observed with selinexor 60 milligrams in combination with ruxolitinib in patients with myelofibrosis, as well as the substantial progression free survival observed in patients with the TP53 wild-type endometrial cancer, which Reshma will expand upon shortly. We are committed to deliver on the opportunities ahead of us and believe selinexor could generate approximately $2 billion of peak annual revenues in the U.S. alone. With a cash runway through late 2025. We have the financial strength to deliver on key data readouts from our three Phase 3 studies. We will continue to be disciplined about our expense management, focusing our resources on our prioritized late-stage pipeline.

As we move to Slide 6, presented here is an overview of the timing of the upcoming key data readouts, which we expect in 2024 and 2025. Each of our ongoing Phase 3 clinical trials, if successful represents an incredibly meaningful growth opportunity for our organization, with the potential to deliver at roughly $2 billion in annual peak revenues. Our proven and established commercialization and late stage development capabilities are focused on executing with our current label, and rapidly progressing these pivotal Phase 3 programs and approval and just one of these in three indications is a transformational opportunity for Karyopharm. And the clinical data that Reshma will review today continues to strengthen our confidence in each of these programs.

With the potential for pivotal catalysts over the next two years, and with the cash runway to deliver on each of these top line readouts. We are well positioned for our next stage of growth. Moving to Slide 7, 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. Turning to Slide 8, we have a very promising late-stage pipeline with pivotal data readouts over the next two years, I will focus on our three Phase 3 trials where our confidence only grows given the positively evolving preclinical and clinical data that support each indication. Each of these trials could position selinexor to substantially change the treatment paradigms in each of these populations, if approved. Turning our attention first to myelofibrosis on Slide 10. Treatment of JAK naive myelofibrosis patients remains an area of high unmet need with more than 20,000 myelofibrosis patients in the U.S. alone. 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 less than 50% of patients achieving an SVR35 and TSS50. 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 cytopenias. On Slide 11, you see that XPOVIO1 inhibition is a fundamental mechanism in myelofibrosis, given that it targets both JAK and non-JAK pathways, underscoring selinexor’s additive or potentially synergistic activity when dosed in combination. Non-JAK mechanisms include inhibition of NF Kappa Beta, induction of cell cycle PH] arrest and P53 driven cell death.

Together XPOVIO1 inhibition increases malignant cell death, decreases malignant cell proliferation and reduces inflammation. We presented updated Phase 1 data at the ASCO and EHA conferences in June, 2023 which can be seen on Slide 12. These data show meaningful SVR35 and TSS50 improvement with 60 milligrams selinexor including a 79% SVR35 and a 58% TSS50 at week 24 in the intent to treat populations. Importantly, amongst the valuable patients 100% achieved in SVR35 at any time. Today at the NPN Congress data are being presented including SVR response and TSS50 durability amongst the 11 out of 14 patients who achieved a 35% or greater spleen volume reduction at week 24. And the seven out of 12 patients who achieved the TSS50 at the same time point.

We are very encouraged by these data given the impressive durability seen on Slide 13 for both of these endpoints. As of August 1st, 2023, none of the week 24 SVR35 responders dosed at selinexor 60 milligrams had observed radiographic progressions. Note that the longest patient has been followed for 78 weeks and the median duration of follow up as of the date of cut off is 32 weeks. Similarly, none of the week 24 TSS50 responders had observed symptom progressions, with the longest follow up of 64 weeks and a median duration of 51 weeks. While I acknowledge the apparent limitations and cross trial comparisons contrast these data to ruxolitinib alone in which only approximately 70% of responses were ongoing at 78 weeks. Data for Ruxolitinib TSS50 durability data beyond week 24 have not been provided.

These data add to the substantial benefit observed with week 24 SVR and TSS50 and highlight the substantial benefit that may be observed with this novel combination compared to ruxolitinib alone. Together these data illustrate the rapid, deep and now durable screen and symptom improvement achieved with selinexor in combination with ruxolitinib and further demonstrate the potential for this combination to change treatment paradigms for JAK naive myelofibrosis patients. This profile in conjunction with the subgroup analysis shown on Slide 14, which depict SVR35 and TSS50 responses, despite treatment with suboptimal doses of ruxolitinib, which is suggestive of potential monotherapy activity underscores our confidence in the ongoing Phase 3 study.

As seen on Slide 15, our Phase 3 study is evaluating the combination of selinexor 60 milligrams with ruxolitinib versus ruxolitinib alone, and 360 JAK naive myelofibrosis patients. This important trial in addition to the Phase 2 selinexor monotherapy trial that we are planning in treatment naive myelofibrosis patients with moderate thrombocytopenia has the potential to entrench selinexor as a foundational therapy in approximately 90% of all treatment naive myelofibrosis patients. As we turn to Slide 17, endometrial cancer is a key focus in our pipeline given the high unmet need and the substantial benefit observed in patients whose tumors are P53 wild-type. Advanced and recurrent endometrial cancer is the most common form of gynecologic cancer in the United States, with the current treatment landscape being driven by molecular classifications.

As a result in MMRD session patients who represent approximately 20% of all advanced recurrent endometrial cancer patients. The new FDA approved standard is Dostarlimab in combination with chemotherapy, followed by Dostarlimab maintenance. For MMR proficient patients which represent the remaining 80% of advanced recurrent endometrial cancer, checkpoint inhibitors are not approved. As such, the primary treatment option is chemotherapy followed by watch and wait. Importantly, wild-type P53 is found in a majority of all advanced recurrent endometrial cancer, as seen on Slide 18. Taken together, patients whose tumors are both MMR proficient and P53 wild-type represent 40% to 55% of all advanced or recurrent endometrial cancer patients. In this substantial population, the benefit observed with selinexor is considerable as seen on Slide 19, given that a 68% decrease in the risk of disease progression or death corresponding to a hazard ratio of 0.32 and a median progression free survival that has not been reached, was observed in this exploratory subgroup of patients from the SIENDO trial as of a March 30th, 2023 data cut off.

The progression free survival results observed in those patients who are P53. Wild-type and MMR deficient are also noteworthy with a median PFS for selinexor of 13.1 month and hazard ratio of 0.45. Further strengthening our rationale and P53 wild-type endometrial cancer are the preclinical data that were recently presented at the AACR-NCI-EORTC International Conference on molecular targets and cancer therapeutics in October. These data from endometrial cancer models further confirm the biology by demonstrating significantly better potency in P53 wild type models as compared to P53 mutant models. Further validating the design of the ongoing Phase 3 study as shown on slide 20. The ECO42 pivotal Phase 3 study is evaluating selinexor as a maintenance therapy in patients with P53 wild-type advanced or recurrent endometrial cancer.

This study will enroll approximately 220 women whose tumors are TP53 wild-type. Ultimately this trial will enable the development of a companion diagnostic and we anticipate the approval of a companion diagnostic would occur at the same time as selinexor if approved. The study is a collaboration between Karyopharm and ENGOT, the European Network for Gynecological Oncological Trial Group and GOG the Gynecology Oncology Group. ENGOT and GOG include the top opinion leaders in gynecology oncology. Their participation in the ongoing Phase 3 studies further underscore the strength of the data observed in the P53 wild-type subgroups and the potential selinexor may have in providing a new standard of care to P53 wild-type endometrial cancer patients.

Together we are making strong progress and have been intensely focused on activating sites and enrolling patients. We are now expecting top line results in the first half of 2025 with the slight timing shift related to countries specific regulatory delays and a few European countries. As seen on Slide 22, 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 a well-established backbone therapy of pomalidomide and dexamethasone. SPD an all-oral combination and evaluated after an anti-CD38 antibody has the potential to benefit a significant number of patients across the multiple myeloma treatment journey. As seen on Slide 23 the Phase 3 trials enrolling patients with relapsed refractory multiple myeloma who have received an anti-CD38 antibody as their most recent therapy.

Patients are randomized one-to-one to the oral regimen of selinexor or pomalidomide and dexamethasone, or elotuzumab, pomalidomide and dexamethasone. The primary endpoint is progression free survival. The potential approval of this combination could lead to the only all oral potentially T-cell sparing regimen for patients with relapsed refractory multiple myeloma, which is gaining increased importance given the incorporation of T-cell therapies in the multiple myeloma treatment landscape. As seen on Slide 24, we are evaluating the effect of selinexor on the immune environment through preclinical translational and real world data as well as clinical trials. We recently announced a collaboration with BMS that will evaluate selinexor in combination with mezigdomide, a Novel CELMoD or Cereblon E3 ubiquitin ligase modulator in triple class exposed multiple myeloma patients.

This combination has the potential to reverse T-cell resistance and builds upon the multiple selinexor combinations that have already demonstrated clinical benefit in multiple myeloma. 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, please turn to Slide 25. And I will now hand it over to Sohanya for a review of our commercial performance for this quarter.

Sohanya Cheng: Thank you, Reshma. And good morning, everyone. On Slide 26. I’m pleased to present the progress we have made in our third quarter performance as we delivered sequential growth in net product revenues over three consecutive quarters in 2023. In an increasingly competitive landscape, and amidst high utilization of free drugs through our patient assistance program, XPOVIO delivered $30.2 million in net sales in Q3. And when compared to Q3 of last year. Net sales were adversely impacted by higher utilization of our patient assistance program due to the impact from myeloma foundation closures, as we have previously discussed. In the third quarter, two of the four main multiple myeloma foundations were open and continue to remain open.

As a result, new patients entering PAP have largely normalized although we saw the refill impact of patients already in PAP earlier in the year. Total PAP utilization contributed to 9% of total demand in Q3, 2023 versus 4% in Q3, 2022. As we’ve mentioned before, in 2024, due to the IRA related changes in the design of Medicare Part D, which will eliminate the patient burden of the 5% beneficiary coinsurance requirement. We expect significantly less need for Medicare Part D patients to utilize PAP for copay assistance. Additionally, net revenue was impacted by two points higher year-over-year gross to net in the third quarter, driven by increased Medicaid rebates and 340B discounts. Total demand year-over-year declined 3% when compared to Q3 of last year, which was our strongest quarter thus far.

Total demand growth year-over-year for Q3 was negatively impacted by increased competition in the late lines in the academic setting. In the earlier lines, we continue to make strong progress. In Q3, 2023 XPOVIO a new patient share mix was greater than 60% in the second to fourth line, which represents approximately 20% growth year-over-year. This shift is mix of patients continues to drive higher refill use as early alive patients tend to stay on therapy longer. Furthermore, our opportunity in the earlier lines is enhanced by the elevation of XPOVIO in the NCCN guidelines to a category one and now preferred regimen in the lenalidomide refractory patient population in relapsed or refractory multiple myeloma. This is meaningful in guiding treatment choices for physicians, particularly in the community, and for patients progressing from regimens like the DARZALEX, Revlimid, dexamethasone combination.

In addition, new subgroup data was presented at the European Hematological Association from our Phase 3 Boston study, which showed that patients that are PI naive or not previously exposed to a proteasome inhibitor and that are treated with XVd showed an approximately tripling of PFS of 29.5 months, versus the control arm VD of 9.7 months. With a hazard ratio of 0.29. Patients are increasingly treated with PI free regimens like the DARZALEX, Revlimid, dexamethasone combination in the front line, which constitutes up to about 10% of frontline patients. With this segment growing over time, as multiple myeloma patients are living longer with the emergence of new classes of therapy. XPOVIO represents an opportunity for these patients to be treated with an effective and novel class of therapy earlier in their treatment journey, and allow for potential sequencing in the future with other classes of therapies.

Our commercialization team is laser focused on sharing our new data, sideline updates and leveraging the experience of a broad base of physicians that have used XPOVIO to drive further use and an early alliance all limits and intensifying competitive landscape in the late lines. We reaffirm our U.S. XPOVIO net revenue guidance of $110 million to $125 million in 2023. Let’s now turn to Slide 27 to review how we are distinctly positioning XPOVIO in the community and academic settings in an evolving landscape. In the community setting while we do see competitive pressures in the late line with some larger accounts, the majority of physicians in the community tend to treat earlier line patients and are looking for agents that are effective, manageable and convenient.

We believe XPOVIO as a novel class that is an effective, manageable, easily combinable and a convenient oral therapy fits the needs of the community well. Furthermore, the NCCN has recently updated their guidelines to recommend switching classes of therapy that patients have not been exposed to previously versus recycling the anti-CD38 class which occurs frequently in the community. This update combined with the elevation of XPOVIO the NCCN guidelines, highlights the importance of changing the mechanism of action with a novel class like XPOVIO. A highly compelling new PI naive subgroup data further strengthens our positioning in the community in the second to fourth line. In the academic setting, where we’re seeing the impact of competition from new approvals, including T-cell therapies.

We continue to build the body of evidence to demonstrate how XPOVIO may be used as an optimal therapy with a novel mechanism of action pre or post T-cell therapies. Also, the opportunity to launch SPD, when approved at the lower dose of 40 milligrams could lead to the only all oral and potentially T-cell sparing regimen. In Q4 we remain focused on entrenching XPOVIO in the community which represents about 60% of our business and driving earlier line growth. While we expect further intensification of the competitive landscape in the late lines. In the mid to long term, we believe that the potential approval of SPD and further data generation around the T-cell fitness space with novel combinations could unlock further benefits for myeloma patients with XPOVIO.

Furthermore Karyopharm has a tremendous opportunity for growth across multiple indications in the future. And we look forward to leveraging our strong commercialization team and capabilities and our deep relationships in the community and centers of excellence for these launches. Please advance now to Slide 28. And I’ll turn the call over to Mike.

Michael Mason: Thank you, Sohanya. During 2023 we have further reduced our cost structure to focus resources on our pivotal Phase 3 trials. And in August, we reduced our workforce by approximately 20%, including contractors. These steps further strengthened our financial position to invest in our three ongoing Phase 3 studies with top line data readouts expected within our cash runway. Now on Slide 29, I will focus on the quarter’s financial highlights. Total revenue for the third quarter of 2023 was $36 million, compared to $36.1 million for the third quarter of 2022. Net product revenue from U.S. commercial sales of XPOVIO to the third quarter of 2023 was $30.2 million compared to $32 million for the third quarter of 2022.

As Sohanya discussed, net product revenue continued to be adversely affected by more patients using our patient assistance program, as well as higher gross to net discounts. Growth connect discounts were 20% in the third quarter of 2023, as compared to 18% in the third quarter of 2022. Turning to costs with our continued focus on cost management, we are pleased to be delivering a combined 12% year-over-year reduction in our R&D and SG&A expenses for the nine months ended September 30th, 2023. R&D expenses for the third quarter of 2023 were $35.6 million, compared to $31.4 million for the third quarter of 2022. We expect fourth quarter 2023 R&D expenses to be relatively consistent to the third quarter as we continue to invest in our three ongoing Phase 3 studies, with each representing a large addressable market with unmet patient needs.

We have reduced SG&A expenses in the third quarter of 2023 by 12% at $30.8 million, compared to $34.6 million for the third quarter of 2022. Cash and cash equivalents restricted cash in investments as of September 30th, 2023 totaled $209.2 million compared to $279.7 million as of December 31st, 2022. Based on our current operating plans, we are reaffirming revenue guidance for the full year of 2023 as follows, total revenue expected to be in the range of $145 million to $160 million. XPOVIO net U.S. product revenue is expected to be in the range of $110 million to $125 million. We’re also reaffirming our expense guidance for the full year of 2023 as follows, non-GAAP R&D and SG&A expenses which exclude stock-based compensation expense is expected to be in the range of $240 million to $255 million.

And importantly, coming to our cash guidance, our existing cash, cash equivalents and investments, as well as the revenue we expect to generate from XPOVIO product sales and other license revenues will be sufficient to fund our planned operations through late 2025, excluding maturity of our convertible bonds in October of 2025. I’ll now turn to Slide 30. And some final thoughts from Richard.

Richard Paulson: Thank you, Mike. Turning to Slide 31. As we have discussed today, we are rapidly advancing our pipeline, concentrating our investments in three Phase 3 programs that are expected to read out through ‘24 and ‘25. As we work to create near and long-term value for all our stakeholders. We are well prepared for the next stage of growth as we continue to expand on our foundation in multiple myeloma. With our proven commercialization and late-stage development capabilities. I would like to thank our teams who continue to execute in a disciplined manner, and who strive each day for patients with high unmet needs. 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: [Operator Instructions] The first question comes from Peter Lawson with Barclays. Please go ahead.

Unidentified Analyst: Hi, good morning. This is Shea [ph] on for Peter, thanks for taking our questions. Congratulations on the new IMF data. Today maybe they’ll contextualize for us as we think about getting that top line data from Phase 3 in 2025. Maybe what the more appropriate bar is to be looking at rather than just JAK inhibitor monotherapy. And then secondly, just a quick add on question for [indiscernible], I believe we’re potentially going to get an update on development plans here. Is that still on track or something we could learn about more in this quarter? Is it something we should be thinking of deprioritized for Karyopharm at this point? Thank you.

Richard Paulson: Thanks Shea, for your question. I will turn to Reshma for this, Reshma?

Reshma Rangwala: Yeah. Thank you. Shea, a lot of excitement around, the new MF data that we are presenting today at the NPN Congress in New York. It only builds upon the impressive efficacy that we see with the combination of selinexor and ruxolitinib in this JAK naive patient population. As you mentioned, we’ve already presented data at week 24, for both SVR as well as TSS50 79%, SVR rate as well as a 58% TSS50 rate. What patients and physicians really want to know is that how long are those SVR and TSS data or response is going to last. And that’s the durability data that we’re presenting today. And what you see is a very impressive durability for both of these endpoints. In fact, as of the data cut off of August 1st, none of the patients experienced a radiographic progression for either SVR or TSS50.

This would again, just build upon the body of evidence that really suggest that this combination could be a game changer for patients who are JAK naive myelofibrosis. And we’ll continue to evaluate this as part of our Phase 3 study right now. The focus is very much on SVR, TSS50 at week 24. But as you mentioned, we’ll continue to look at durability as well as multiple other efficacy endpoints that are relevant to this patient population. In regards to your question about the appropriate comparator, it still remains ruxolitinib. So, ruxolitinib is the standard of care for patients who are JAK naive myelofibrosis who have platelet counts above 100. So, the study design is appropriate and evaluates again, the efficacy with this combination relative to the current standard of care.

In terms of your question about eltanexor, great question. Very enthusiastic about those data as well specifically observed from the phase one phase two study. We have been evaluating eltanexor in a very hard to treat patient population specifically relapsed refractory higher risk MDS patients, overall survival is very poor in this patient population around four to six months. And as we’ve disclosed previously, the survival that we’ve seen as part of both the Phase 1 and Phase 2 are very encouraging, right, nine-to-10-month median overall survival. We are in the process of optimizing our next steps in this program, and look forward to updating everybody probably around the Q4 call.

Operator: Was there a follow up, ma’am?

Unidentified Analyst: Okay, thanks so much.

Operator: Thank you. The next question comes from Maury Raycroft with Jefferies. Please go ahead.

Maury Raycroft: Hi, good morning. Congrats on the progress. And thanks for taking my questions. I was going to ask one on endometrial. So, for selinexor as maintenance and endometrial. When do you think you could show the initial overall survival data from the SIENDO Phase 3 study? And then also separately, how is the export Phase 3 in the TP53 wild-type patients enrolling? And do you have a sense of how many patients are getting anti-PD1 therapy with chemo upfront? If you can provide any perspective on that?

Reshma Rangwala: Yeah, great question. Maury. So, as you know, so we continue to follow overall survival. We are very excited; we are going to be presenting overall survival data for the first time from the SIENDO trials specifically from the P53 wild-type subgroup later this year. So, more to come in the next couple of months. Obviously, a key endpoint in addition to the progression free survival, some more to come over there. In terms of the question around the PD1 inhibitors in combination with chemotherapy. So there is a new standard as I mentioned on the call, it is Dostarlimab in combination with chemotherapy followed by Dostarlimab maintenance. Keep in mind that the approval is only for patients who are MMR deficient, so they represent the minority of patients and only 20%. The remaining patients who are PMMR are proficient in their MMR as well as TP53 do not have a new standard of care, continues to remain chemotherapy followed by watch and wait.

Maury Raycroft: Got it. That’s helpful. And any other perspective into enrollment and how that’s going. And then also wanted to ask a separate question on multiple myeloma commercial. You said there were approximately 20%. There was 20%, year-over-year growth in second line to fourth line new starts. Can you give us some color on how repo rates have evolved, specifically in these early line patients, versus when you were just in the later line setting?

Richard Paulson: And maybe I’ll turn to Reshma. Just to follow-up on the trial question, and Sohanya on the progress in multiple myeloma. Reshma?

Reshma Rangwala: Thank you. So, enrollment is going well, there’s a lot and largely to do just from the enthusiasm around these data. And I think that was highlighted most recently at ESMO. A couple of weeks ago in Spain, a lot of enthusiasm largely because the benefit that we are demonstrating is again, in the high unmet need patient population that doesn’t have a new standard of care. That is translating to activation insights, and enrollment onto our clinical trials, we in fact, have 70 plus sites that are already active and enrolling patients onto the study. So, the study is going — it’s proceeding quite nicely

Sohanya Cheng: And I can address the question around 20% year-over-year growth. So, when you look at our mix of XPOVIO new starts, over 60% of that is in the second or fourth line, which represents in Q3 year-over-year, a 20% growth. Now, the shift into earlier lines, as you pointed out is a huge growth driver for us, primarily because of the benefit of duration that we see. Now as we think about duration of therapy data. As we’ve discussed previously, the data can be choppy, takes time to mature. But as we triangulate multiple data sources, we are seeing a nice upward trend in our duration of therapy and refills. And this is largely driven by this increasing patient on the earlier lines. And also better management of patients on the lower dose and supportive care.

Maury Raycroft: Got it. That’s helpful. Thanks for taking my questions.

Operator: [Operator Instructions]. The next question comes from Colleen Kusy with Baird. Please go ahead.