Karyopharm Therapeutics Q1 2024 Earnings Call Transcript

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Provided by Quartr
May 8, 2024

There are 12 speakers on the call.

Operator

Good morning. My name is Liz, and I'll be your conference operator today. At this time, I'd like to welcome everyone to the Karyopharm Therapeutics First Quarter 2024 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 Elhan Webb, Senior Vice President, Investor Relations.

Speaker 1

Thank you, Liza, and thank you all for joining us on today's conference call to discuss CaraPharm's Q1 2024 financial results Company progress. We issued a press release this morning detailing our financial results for the Q1 2024. 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, Solani and Mike, who will provide an update on our Q1 results and recent financing transactions that we announced this morning as well. Before we begin our formal comments, I'll remind you that various remarks we'll make today constitute forward looking statements, or FLS, 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 FLS as a result of various important factors, including those discussed in the Risk Factors section of our most recent Form 10 ks, 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 this FLS as representing our views as of any later date. I will now turn the call over to Richard.

Speaker 1

Please turn to Slide 4.

Speaker 2

Good morning. Thank you, Alhan, and thank you all for joining today for Karyopharm's Q1 2024 earnings call. As you have seen, this morning we have shared important news from a financial perspective that strengthens our potential to deliver on our innovation and growth strategy. I'll touch more on this in

Speaker 3

a moment. Turning

Speaker 2

to Slide 5, we have had a strong start to the year as we work to deliver our next stage of growth and advance our late stage pipeline with trials that have the potential to enhance and create new standards of care for patients, while providing significant value creation opportunities in the near term. Raishma will talk to our pipeline progress. Commercially, in the United States, we are pleased with our results this quarter in the highly competitive multiple myeloma market, including EXPOLVIO's rolling roll pre and post T cell therapies. Additionally, with our partners, we continue to expand selinexor's presence, including recent reimbursement decisions in both China and the United Kingdom. So Hany will talk to our commercial performance in the quarter.

Speaker 2

As we look to the future, the commercial infrastructure that we build provides us with the capability to support the rapid and smooth commercial launch of selinexor in new indications if approved. We continue to believe that selinexor can generate up to $2,000,000,000 of annual peak sales in the United States alone, depending on the outcome of our 3 pivotal Phase 3 data readouts in 2025. As seen on Slide 6, importantly from a financial perspective, we have taken a significant step that improves our capital structure, strengthening our opportunity to realize the full value of our late stage pipeline. Our comprehensive refinancing and amended royalty agreement announced this morning extends the vast majority of our debt maturities into 20282029, well beyond the expected data readouts and potential approvals of our 3 Phase 3 programs. Finally, through continued disciplined execution and a concentrated pipeline, we have an expected runway into the end of 2025, providing us with the financial strength to deliver on our pivotal data readouts.

Speaker 2

Mike will discuss the details of the refinancing later on the call. Moving to slide 7, I would now like to turn the call over to Reshma to expand further on our pipeline and the progress we have made. Reshma?

Speaker 4

Thank you, Richard, and good morning, everyone. On Slide 8, you can see our 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. Turning our attention to endometrial cancer on Slide 10. Endometrial cancer is a key focus in our pipeline given the high unmet need and 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 approximately 16,000 patients diagnosed each year.

Speaker 4

The evolving treatment landscape is being driven by molecular classifications. 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 gestarlomab maintenance. For PMMR, which represents the remaining 80% of patients, the primary treatment option is chemotherapy followed by watch and wait. Despite the availability of the checkpoint inhibitors, given the limited efficacy achieved with these agents in this molecular subgroup. DP53 wild type represents a potentially unique, but fundamental biomarker as it is found in the majority of all advanced recurrent endometrial cancer.

Speaker 4

As seen on Slide 11, patients whose tumors who are both PMMR and p53 wild type represent 40% to 55 percent of all advanced or recurrent endometrial cancer patients. The long term follow-up data from the TP53 wild type sub maintenance therapy, has generated substantial enthusiasm from the medical community and highlights selinexor's potential to meaningfully improve outcomes for patients with TP53 wild type endometrial cancer. With the paradigm shift underway, opinion leaders confirm there is a clear unmet need for patients whose tumors are p53 wild type and emphasize the opportunity for new agents. On Slide 12, you can see this long term follow-up data with selinexor treatment. After completion of approximately 6 months of chemotherapy showed a median PFS for selinexor of 27.4 months and 5.2 months for placebo corresponding to a hazard ratio of 0.41.

Speaker 4

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 XP01 inhibition retains p53 within the nucleus, thus enhancing cell kill. As shown on slide 13, 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 has not been reached as of our most recent data cutoff presented. These efficacy data coupled with a generally manageable side effect profile suggest that oral selinexor is uniquely positioned as an optimal maintenance therapy where convenience, tolerability and meaningful efficacy in a precise patient population are the hallmarks of the maintenance option. We look forward to the oral presentation at the ASCO meeting in June, where additional follow-up data and new analyses from this important TP53 wild type subgroup will be reported. On slide 14, you can see the design of our EC-forty 2 pivotal Phase 3 study, which will enroll approximately 220 women whose tumors are TP53 wild type.

Speaker 4

We look forward to presenting top line results from this pivotal trial in the first half of twenty twenty five. Let's now move to myelofibrosis. As you can see on Slide 16, 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 or less and half of those patients achieving a meaningful symptom improvement. Xpi01 inhibition is a fundamental mechanism in myelofibrosis given that it targets both JAK and non JAK pathways, underscoring selinexor additive if not potentially synergistic activity when dosed in combination.

Speaker 4

As you can see on slide 17, we presented updated data last year from our trial evaluating selinexor 60 milligrams with ruxolitinib in JAK inhibitor naive patients. Amongst the 14 patients enrolled to the selinexor 60 milligram dose, a 78% SVR35 at week 24 was observed in the ITT population. Importantly, amongst the evaluable patients, 100% achieved in FCR35 at any time. As we move to Slide 18, when we look at FCR35 and TSS 50 together, we see that 50% of patients experienced both of these responses at week 24 and 75% experienced both SVR35 and TSS 50 response at any time. On slide 19, both TSS-fifty and absolute TSS showed very meaningful improvements at week 24.

Speaker 4

58% of ITT and 78% of the efficacy evaluable achieved a TSS-fifty response. For absolute TSS, an average 18.5 point improvement was observed in the efficacy of valuable population at the same time point. Compare these historical ruxolitinib data where TSS-fifty was observed in 42% to 46% of ruxolitinib treated patients and the average TSS improvement was 11 to 14 points. All symptom domains were substantially improved with selinexor combination and showed that pro inflammatory cytokines demonstrated rapid deep and sustained reductions relative to baseline. Taken together, these data validate 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.

Speaker 4

The subgroup analysis shown on Slide 20, which depicts FCR35 and TSS50 responses despite treatment with suboptimal doses of ruxolitinib is suggestive of potential monotherapy activity. To further demonstrate selinexor's potential fundamental role in myelofibrosis and to build upon the growing data demonstrating monotherapy activity in both treatment naive and JAK exposed myelofibrosis patients, we have initiated the CENTREAT 2 Phase 2 trial as you see on Slide 21. This trial will include treatment naive myelofibrosis patients with moderate thrombocytopenia and has the potential to entrench selinexor as a foundational therapy in approximately 90% treatment naive myelofibrosis patients. As the body of our data grow and positively evolve, we see increasing interest from the medical community on the potential of selinexor in myelofibrosis. We maintain a high level of confidence in our ongoing Phase 3 shown on Slide 22, which evaluates the combination of selinexor 60 milligrams with bruxolitinib versus bruxolitinib alone in 306 JAK naive myelofibrosis patients.

Speaker 4

We remain on track to report top line results in the second half of twenty twenty five. Turning now to multiple myeloma. There is a growing need being discussed amongst myeloma thought leaders to identify and incorporate therapies early into a patient's treatment journey that do not deteriorate a patient's T cell levels and which can be used pre and post T cell redirecting therapies such as bispecifics and CAR Ts. We have been building a body of evidence around selinexor's role in preserving cytotoxic T cell function. As seen on Slide 24, we are further evaluating the effect of selinexor on the immune environment through preclinical, translational and real world data as well as clinical trials.

Speaker 4

We have also been hearing encouraging feedback on the positive evolution of EXPOLVIO, its effectiveness and tolerability at the lower doses real world outcomes observed with use in combination with a well established backbone therapy of pomalidomide and dexamethasone. Seen on Slide 25, we are evaluating selinexor at the low dose of 40 milligrams with this combination in our ongoing Phase 3 trial post anti CD38 antibodies. We expect to report top line data from this trial 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 upon our approved indications. With that, I will now hand it over to Silhania to review our commercial highlights.

Speaker 5

Thank you, Reshma. Turning now to Slide 27, I will discuss our commercial highlights for the Q1 of 2024. In the Q1, exfoliovio net product revenue was $26,000,000 minus 8% year over year and plus 4% quarter over quarter amidst increased competition. Quarter over quarter growth was driven by an increase in new patient starts and partially offset by a softness in refills due to the impact of fewer new patient starts in the prior quarter. Additionally, a higher gross to net discount typical of what we see in the Q1 of the year adversely impacted exovio net product revenue this quarter.

Speaker 5

The community setting contributed to roughly 60% of exfoliovo's net revenues in the Q1. There was increased breadth of use as we added new community prescribers to our customer base and growth in new patient starts offset by softness in refills. This is encouraging as new patient starts have the potential to positively impact exfolio net product revenue in upcoming quarters. In the academic setting, there was quarter over quarter growth in demand as EXPOVIO continues to fulfill patient needs in an evolving competitive multiple myeloma landscape. As Reshma mentioned, XPO1 inhibition provides patients with a potentially T cell sparing treatment option before or after T cell therapies.

Speaker 5

This advantage places selinexor in a flexible position in the treatment paradigm as a novel mechanism of action. In the Q1, EXPOVIO's new patient mix in the second to fourth lines stayed stable quarter over quarter. As we look ahead, we expect to see continuation of selinexor treatment in second to fourth lines, primarily in the community setting and in later lines in the academic setting, typically pre or post T cell therapies. In a highly competitive multiple myeloma landscape, our team is executing with resilience to drive an increasingly important role for selinexor in the treatment paradigm as a novel effective treatment option for patients. We are reaffirming exfoliovio's 2024 net product revenue guidance of $100,000,000 to $120,000,000 Now turning to Slide 28 and shifting to achievements in the ex U.

Speaker 5

S. As exovio continues to expand its global footprint, we are pleased with the positive recommendation the positive recommendation

Speaker 3

by NICE in the

Speaker 6

United Kingdom

Speaker 5

for reimbursement of selinexor in the earlier line treatment setting, inclusion in China's national 2024 and approval for reimbursement in Germany. In conclusion, our multiple myeloma franchise continues to positively impact more patients every year, while being a key driver in funding our pipeline. Our strong commercialization team is focused on expanding our multiple myeloma business and rapidly launching in potential future indications. Now I would like to turn the call over to Mike to discuss our recently announced transactions and give an update on our financials.

Speaker 3

Good morning, everyone, and thank you, Sohanya. Before turning to our 1Q 2024 financial results, I'm incredibly pleased to announce we've extended the vast majority of our debt maturities into 20282029 well beyond expected data readouts from our 3 Phase 3 trials and potential launches positioning Karyopharm sustainable value creation. Now I will walk you through these series of refinancing transactions announced this morning and as outlined on Slide 30, you can see the impact on our balance sheet. First, we retired approximately $148,000,000 or 86 percent of the $172,500,000 existing convertible notes due in 2025 for approximately $111,000,000 of newly issued secured convertible notes due in 2029. This exchange is at a 25% discount to par.

Speaker 3

We now have $24,500,000 remaining of the existing convertible bond due in October 2025. In addition, Healthcare Royalty or HCRX purchased $5,000,000 of the 20 29 convertible notes. 2nd, we issued a new $100,000,000 senior secured term loan due in 2028 with $85,000,000 committed from certain existing convertible note holders and $15,000,000 from HCRX. We used $49,500,000 of the proceeds along with $5,000,000 in 20.29 convertible notes and $15,000,000 of the secured term loan to HCRX to satisfy the remaining principal portion under our existing agreement with HCRX. Lastly, we amended our existing agreement with HCRX eliminating any potential gross up payments and reducing the royalty rate on net revenues to 7%, down from 12.5%.

Speaker 3

Overall, you can see the difference in our debt maturity profile on the right side of the slide. Net net, our total liabilities are reduced slightly and additional approximately $30,000,000 of cash strengthens our balance sheet with cash runway into the end of 2025. The confidence and continued support in Karyopharm's future from Healthcare Royalty and our top convertible note holders reflects their confidence in the potential of selinexor in our late stage pipeline programs. These transactions represent a fundamental change and benefit to our capital structure and the financial health of the company, strengthening our opportunity to deliver the value of our late stage pipeline as we provide benefit to patients in need of new treatment options. 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 are on Slide 31.

Speaker 3

Total revenue for the Q1 of 2024 was $33,100,000 compared to $38,700,000 for the Q1 of 2023. Net product revenue from U. S. Commercial sales of XPOVIO for the Q1 of 2024 was $26,000,000 compared to $28,300,000 for the Q1 of 2023. The gross to net discount for XPOVIO in the Q1 of 2024 was 29%.

Speaker 3

As a reminder, gross to nets are typically higher in the Q1. We expect gross to net discounts to be in the 25% to 30% range for the full year 2024. Our total expenses for the Q1 of 2024 were down year over year 4%, reflecting our ongoing cost reduction initiatives and focus investments in our late stage pipeline. R and D expenses for the Q1 of 2024 were $35,400,000 compared to $32,300,000 for the Q1 of 2023. The increase in R and D expenses is primarily attributable to higher clinical trial costs related to the advancement of our 3 pivotal Phase 3 programs.

Speaker 3

SG and A expenses for the Q1 of 2024 were $29,500,000 compared to $35,900,000 for the Q1 of 2023. The decrease in SG and A expenses was primarily due to our ongoing cost reduction initiatives and lower headcount. Cash, cash equivalents, restricted cash and investments as of March 31, 2024 totaled $149,300,000 compared to $192,400,000 as of December 31, 2023. Based on our current operating plans, we are reaffirming revenue guidance for the full year of 2024 as follows: total revenue expected to be in the range of $140,000,000 to 160,000,000 dollars exovio net U. S.

Speaker 3

Product revenue expected to be in the range of $100,000,000 to $120,000,000 We're also reaffirming our expense guidance for the full year of 2024 as follows: R and D and SG and A expenses are expected to be in the range of $260,000,000 to $280,000,000 which includes approximately $20,000,000 to $25,000,000 of estimated non cash stock based compensation expense. And finally, we expect our existing cash, cash equivalents and investments as well as the revenue we expect to generate from exfolvio net product sales and other license revenues will be sufficient to fund our planned operations into the end of 2025. In summary, we have taken significant steps to improve our capital structure with our recent debt exchange and amended agreement with Healthcare Royalty. We are rapidly advancing our 3 Phase 3 trials and driving commercial performance, while continuing to be very diligent when allocating our resources. I'll now flip to Slide 32 and turn the call over to Richard for some final thoughts.

Speaker 3

Richard?

Speaker 2

Thank you, Mike. As you can see on Slide 33, we have several key milestones across 2024 2025 and are pleased to have extended the vast majority of our debt maturities into 20282029 well beyond the data readouts and potential approvals of our 3 Phase 3 programs. With the substantial improvement in our capital structure, we have strengthened our opportunity to realize the full value of our late stage pipeline with our Phase 3 clinical trials in multiple myeloma, endometrial cancer and myelofibrosis, each of which would be transformative for patients and our organization. With data expected from each of these pivotal trials in 2025, next year is going to be an incredibly exciting time for our organization as we believe the largest opportunities for selinexor are yet to come. We are focused on delivering on our next phase of growth and our organization continues to be fueled by our belief in the extraordinary strength and courage of patients with cancer and the potential of our novel mechanism of action to positively impact their lives.

Speaker 2

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

Operator

Thank you. Ladies and gentlemen, we will now begin the question and answer And your first question comes from the line of Chris Raymond from Piper Sandler. Please go ahead.

Speaker 6

Hey, thanks for taking my question. Just a couple quick ones here. Just on the refinancing and the amended royalty agreement. So there's a lot of moving parts here and I don't think I saw any description of this. You guys have been carrying a pretty consistent interest expense each quarter.

Speaker 6

Can you maybe just sort of boil us down to what the projected new quarterly interest expense might look like? That's the first question. Then secondly, I know you guys have talked for quite a while about the competitive environment between the for ex povio between the sort of academic and community settings. And I think in your prepared comments, you mentioned that gross to net spreads this quarter were fairly consistent with what you'd expect in the Q1. But is there any sort of difference in gross to net spreads between the two settings that you can describe?

Speaker 6

Thanks.

Speaker 2

Yes. Thanks, Chris. As I mentioned, I think a lot of excitement around being able to fundamentally adapt our balance sheet and really strengthen as we move forward. So for the first part of your question, I'll turn to Mike to really talk about from a cash perspective and looking at our interest expense.

Speaker 3

Thanks, Richard. Yes, at a high level, these transactions certainly strengthen our cash balance and improve our cash runway into the end of 2025 beyond our expected data readouts in 2025 based on our current operating plans. And to your specific question on interest expense, so there's 2 components of interest expense for us. There's our interest on our debt as well as our royalty agreement with ACR, which is recorded through interest expense. So going forward, we expect interest expense this year to be around $18,000,000 for the debt component, so that excludes HCR.

Speaker 3

And then if you saw as part of the refinancing, we amended our HCR agreement to reduce our royalty rate from 12% to 7%. So for the rest of this year, we expect that number based on our revenue guidance to be around $8,000,000 So if you combine the 2 together, that's what you'll see. Okay. Thank you.

Speaker 2

Yes. And for the second part, Chris, when you look at the GTN between the community and the academic, I mean, overall, I think as we've talked to the GTN is up 6 points. And so when I look at it, I think it's quite difficult to break it out, really depends on source of business within each one of those areas versus kind of a general statement across academic and community.

Speaker 3

Yes, I would just add, yes, book mix of business is really the key that drives GTN unusually in Q1 up, so that starts higher in the year. So we think we'll still end up in that range of 25% to 30% with some volatility each quarter.

Speaker 6

Thank you.

Speaker 3

Thanks, Chris.

Operator

Your next question comes from the line of Peter Lawson from Barclays. Please go ahead.

Speaker 7

Hi, good morning. This is Alex on for Peter. Thank you for taking our questions. Just we have two questions on the endometrial program. Just wondering if you could what should what could we learn from the updated SIENDO data at ASCO?

Speaker 7

What do you think investors should focus on there? And then related, any differences in the patient population in SIENDO compared to the ongoing pivotal study that we should keep in mind? Thank you.

Speaker 2

Thanks, Alex. For that, I'm going to turn to Duraishma to talk through that.

Speaker 4

Yes. Thanks, Alex, for the great question. So a couple of highlights around ASCO. So first off, it's really an honor from ASCO. We were actually invited to present an update on the p53 wild type subgroup.

Speaker 4

And this is a follow on from the ASCO plenary last year. I think it resonated with a lot of KOLs. ASCO again really wanted us to perform an update from that p53 wild type subgroup. So at this upcoming ASCO, we're going to use this opportunity to really update both efficacy as well as safety and provide some new analyses that I think will further highlight the potential benefit risk that we see with selinexor in this novel population of p53 wild type endometrial cancer. So can't go into more details, but really looking forward to this opportunity.

Speaker 4

And I want to thank Vicki Macher at MSK for presenting on behalf of all of the investigators. In terms of your second question, so really the main differences in this trial relative to SIENDO, once again, it's going to be that patient population. So SIENDO enrolled in all comers population in that all patients with advanced or recurrent endometrial cancer were potentially eligible to be randomized. In the current trial, we're just focusing on those patients who have p53 wild type, which is evaluated by NGS testing with our partner Foundation Medicine. The other key difference, not necessarily related to the patient population, but an important difference is the dose.

Speaker 4

So in SIENDO, we treated everybody with a dose of selinexor at 80 milligrams weekly and this current trial, it's going to be 60 milligrams weekly. So those are the two main differences that I would highlight across the two trials.

Speaker 2

Thanks, Alex.

Operator

Thank you. And your next question comes from the line of Maury Crayford from Jefferies. Please go ahead.

Speaker 8

Hi, good morning. Thanks for taking my question. I was going to ask a couple more specifics on the upcoming data at ASCO. So late last year, you guys presented some initial OS data at the IGCS conference and also in your last cut, medium PFS in the PMMR group was not immature. For the data at ASCO in a couple of weeks, can you say if you're going to have an update on PFS in the PMMR group and also on OS for this study?

Speaker 8

And, yes, maybe I'll start with that question.

Speaker 4

Yes. Thanks, Maury. Really appreciate the question. So I can't at this point just provide any additional details in terms of the exact analyses that we're going to present. Just keep in mind again, we are going to have an opportunity to present updates on efficacy, so both PFS and then these new analyses, right?

Speaker 4

So that will provide additional color on the benefit risk. So more to come in the next few weeks, but really excited to be able to provide this update.

Speaker 8

Got it. That's helpful. And when you speak with doctors about what doctors want to see as on OS, what's the landmark OS that you want to achieve in this study? And also can you talk about some of the drivers of OS that you're focused on in C and O?

Speaker 4

Yes. So the trial is powered to detect a meaningful and statistical difference in terms of PFS, so progression free survival, very similar to the SIENDO trial and very similar to the endpoints in which dastarlimab was approved in combination with chemotherapy followed by dastarlimab maintenance specifically in that DMMR patient population. So the focus is very much going to be on PFS. With that said, OS is a key secondary endpoint and the goal is to really show no detriment at the time of the primary cutoff. And we define no detriment specifically by a hazard ratio of less than 1.

Speaker 4

In terms of the actual median overall survival, I think that's going to take some time for it to mature. These patients are living longer and longer and we'll continue to follow that overall survival. And as that data matures from this ongoing trial, we'll be able to provide those additional data at future with future updates.

Speaker 8

Okay. And just to clarify, is there a benchmark or some sort of a landmark in SIENDO on OS that you want to achieve or that doctors would want to see for that study?

Speaker 4

No, not at this time. I think it's very much evolving. So at this point, I don't have a landmark to be able to provide. Again, I think the focus very much is the no detriment that I mentioned earlier.

Speaker 8

Got it. Okay. And then maybe one last question and then I'll hop back in the queue. You said you could have myelofibrosis Phase 1 data update this year. What could that look like and what venue would make sense for that update?

Speaker 4

Yes. So I think the focus really is going to be on that CENTURY-two trial. So CENTURY-two, it's a new acronym for the trial, but it is that 0.044 trial that we alluded to at JP Morgan. This is that selinexor monotherapy trial that we're evaluating in the JAK naive patient population. That is going to be our focus for this year.

Speaker 4

And we anticipate being able to provide some initial preliminary data, both from an efficacy as well as a safety perspective, sometime in 2024. With that said, the Phase 1 selinexor ruxolitinib trial is still ongoing as well, and we'll be able to provide some additional updates both in efficacy and safety perspective later this year as well.

Speaker 8

Okay, great. Thanks for taking my questions.

Speaker 2

Thanks, Laurie.

Operator

And your next question comes from Colleen Cussey from Baird. Please go ahead.

Speaker 9

Great. Good morning. Thanks for taking our questions and congrats on the refinancing. One on the endometrial Phase 3, How do you expect the enrollment in the Phase 3 will be split among the PMMR and DMMR patients? And what are the characteristics you're stratifying for and would that include MMR status?

Speaker 9

And then I have a follow-up.

Speaker 4

Yes. Great question and thank you, Colleen. So when we look at the endometrial cancer patient population and specifically MMR, the vast majority of patients are going to be that PMMR. They comprise approximately 80% of all patients. When we look at the remaining population or 20%, they're going to be in that DMMR patient population.

Speaker 4

When we look at the P53 subpopulation that breakdown of 8020 is going to be similar within that p53 wild type subgroup. If I have to anticipate the proportion of patients who are DMMR to be enrolled in this trial, I would assume somewhere less than 10%, maybe between 10% 20%, very similar to what we are seeing in the natural population. Yes.

Speaker 9

And is that something you're stratifying for? What are the items that you're stratifying for in that Phase 3 enrollment?

Speaker 4

We're not stratifying yes, thank you for that follow-up. So we're not stratifying, based upon MMR status. So again, because we assume that the majority of patients are going to be PMMR, we assume that there's going to be a similar split across the two arms selinexor and placebo. So again, not stratifying.

Speaker 9

Understood. Helpful. Thank you. And then, in myelofibrosis, I know your ongoing Phase 3 has the co primary endpoint of both SBR-thirty five and TSS-fifty. Just curious if you had any recent interactions with the FDA on kind of the role of TSS-fifty specifically and kind of how you're thinking about the approval endpoints of myelofibrosis?

Speaker 4

Yes. So we don't comment on the specifics with our FDA interactions. With that said, I think in the myelofibrosis space, the focus has always been and continues to be on 2 main endpoints. This is going to be SVR35 as well as TSS analyses and the precedent has always been 50%. So we're very much focused on those endpoints and very encouraged by our Phase 1 data, which really suggests that the combination of selinexor plus ruxolitinib can maximize the benefit we see across these two endpoints.

Speaker 4

It continues to remain that. If you add additional DOR data, it really demonstrates that the patients, once they achieve that SVR35 or TSS50, will remain in those responses. So really encouraged by the compilation of data and I think it just provides further confidence in the potential outcomes for our Phase 3 trial.

Speaker 9

Great. Thank you. And then one commercial question, if I can. Zohania, in the pre and post T cell therapy setting, can you just speak to the type of duration of treatment you're seeing in that patient population versus what you see on average in the second to third line setting or second to 4th? Thanks.

Speaker 5

Yes, absolutely. So there's several ways that selinexor can be used pre and post, as well as hairy T cell therapies. It can in the pre stage, it can be used as a shorter bridge, which could be one cycle or it can be used as a unique line of therapy preceding a T cell therapy, which could be several months long. Now, as you look at the different puts and takes of duration of therapy, there's a couple of key drivers. One is the new patient start volume, right?

Speaker 5

So no higher the new patient starts, you hire your refills. The good news in Q1, we saw a really nice growth versus the prior quarter in new patient starts in the academic setting as well as the community setting. The second area around duration of therapy is how long patients stay on therapy. That is really driven by a couple of different factors. One is what lines of therapy they are on, earlier lines patients stay on therapy longer, that's typically in the community, as well as we've got the offset or balance in the academic setting that we see with the bridge.

Speaker 5

So our goal in balancing out that shorter duration with the bridge in the academic setting is to continue to drive that new patient volume in that pre and post T cell therapy space.

Speaker 9

Great. Thanks for taking our questions.

Speaker 2

Thanks, Colleen.

Operator

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

Speaker 10

Hi there. Good morning. Thanks for taking my questions. 2 for me. I guess first on the endometrial Phase 3, I understand the majority of the patients are likely to be PMMR.

Speaker 10

But I guess I'm curious in light of the maturing data and the longer capital runway now, whether you had any updated thoughts on whether you might consider focusing enrollment for the primary analysis on that PMMR population? Would there be any reason not to do that? And then secondarily, with regard to the updated agreements, any changes to the change in control provisions? I recall previously there were some gross ups in that situation. And just wondering if those are still there or if those have been eliminated as well.

Speaker 10

Thanks.

Speaker 2

Thanks, Brian. Maybe I'll turn to Duraishma to talk to the first part and then Mike to talk to the second part.

Speaker 4

Yes. Thanks, Brian. Great question. One of the reasons that we're focusing on both the PMMR as well as the DMMR patient populations is because if you look at the hazard ratio across the 2 subgroups, they show very meaningful benefit. So in that PMMR p53 wild type subgroup, we're seeing a very impressive 0.32 hazard ratio.

Speaker 4

But when you look at the DMMR patient population, you're also seeing a very strong approximately 0.4 hazard ratio. So the benefit is really seen regardless of MMR status. And it really suggests to me at least that the key biomarker that is driving or predicting the benefit is all going to is going to be about that p53 status. So right now we really want to leverage that p53 status and patient population based upon that unique biomarker and be able to ultimately drive use across this broad population.

Speaker 2

Yes. And for the second part, when we look at the updated agreement, so I'll turn to Mike to touch on that point.

Speaker 3

Sure, Brian. And especially, I think you're referring to the amended agreement with HCR. So that still stays consistent where in that case they do get their return is capped at 1 point 9 5x, so that would stay the same. And as far as the convert, we have customary make whole provisions in the agreement.

Speaker 7

Thank you.

Speaker 2

Thanks, Brian.

Operator

Your next question comes from the line of Ed White from H. C. Wainwright. Please go ahead.

Speaker 2

Good morning. Thanks for taking my questions. Just one for me. The SGA has trended lower and I was just wondering if with all your cost reductions, are they all in place now? Is the sales force right size now?

Speaker 2

And are you expecting to see further lower expenses in SG and A? Or are we sort of at a more stabilized level now? Thanks. Yes. Thanks, Ed.

Speaker 2

I think as you know, we've had a strong focus on really being very diligent with regards to our capital allocation, reducing headcount and being very focused in our pipeline. And we've been able to obviously see those benefits come through over the last year. And overall those benefits will continue. And we don't see the focus right now is on our late stage pipeline and we're going to continue that focus. At the same time, our commercialization capability and our commercial team as we talked to, is profitable with regards to our multiple myoma business, right now, driving a 2 to 1 ROI and really helping to fund our pipeline.

Speaker 2

So I think we have the right resources in place. And maybe Mike, do you want to add some more detail? Yes, just

Speaker 3

a little more detail. I mean, I think we've been running right around 30,000,000 Q3 last year, Q4 last year, Q1 this year, and we expect it to be consistent going forward.

Speaker 2

Okay, great. Thanks for taking my question.

Speaker 3

Thanks, Ed. Thanks, Ed. Thank

Operator

Your next question comes from the line of Jonathan Chang from Leerink Partners. Please go ahead.

Speaker 11

Hi, guys. Good morning and thanks for taking my questions. We're still working through the math on the refinancing agreements and amendments announced this morning. So just a couple of hard level questions for now. One, what are the key implications of these agreements for the equity holder?

Speaker 11

And 2, what is the impact of these agreements on your cash runway guidance? It doesn't seem to have moved that much, but I might

Speaker 6

be missing something. Thank you.

Speaker 2

Yes. I think we'll turn to Mike and maybe Mike we start with number 2 first and then go to number 1.

Speaker 3

Sure. Our cash runway guidance is now into the end of 2025. So it was between the $30,000,000 of cash coming in, our current operating plan as well as the new interest payments offset by the lower royalty payments take us into the end of 2025? And then you want to touch on the first part? I'm happy to.

Speaker 3

So I think overall, the important thing here for equity holders is there's a lot of excitement around our Phase 3 program. So we want to strengthen our balance sheet to unlock value by extending maturity of our debt obligations well beyond our planned data readouts and potential approvals. So we took advantage of the convert trading at a discount and exchange them at a 25% discount to par. From a timing perspective, why now? We wanted to address this before it becomes current.

Speaker 3

So as we've said in the past, we really want to address this within 12 to 24 months maturity and we're sort of right in the middle of that sweet spot. So overall, we're pleased to have the vast majority of our debt obligations well beyond our expected data readouts and potential approvals.

Speaker 11

Got it. Thanks for taking the questions.

Speaker 2

Yes. Thanks, Jonathan.

Operator

Thank you. There are no further questions at this time. And I'd like to hand over the call to Richard Paulson for closing remarks.

Speaker 2

Thank you, operator, and thank you again to everyone today for joining us. As we've really highlighted on the call, we're very pleased with the substantial improvement in our capital structure. We've strengthened our opportunity to realize the full value of our late stage pipeline and with our 3 Phase 3 clinical trials. We've touched on the fact that each one of them would be transformative for patients and transformative for organizations. So we're continuing to be focused on delivering our next stage of growth.

Speaker 2

And once again, I want to thank you for joining us today.

Operator

Thank you. Ladies and gentlemen, this concludes today's conference call. You may now disconnect.

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Earnings Conference Call
Karyopharm Therapeutics Q1 2024
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