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spk07: 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 CarioFarm 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. I would now like to turn the call over to Alhan Webb, Senior Vice President, Investor Relations.
spk10: Thank you, Lysol, and thank you all for joining us on today's conference call to discuss CARA Farm's first quarter 2024 financial results and recent company progress. We issued a press release this morning detailing our financial results for the first quarter 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 two, I'm joined by Richard, Reshma, Sohani, and Mike, who will provide an update on our first quarter 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 will make today constitute forward-looking statements, or FNS, for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide three. Actual results may differ materially from those indicated by these FLS as a result of various important factors, including those discussed in the risk factors section of our most recent form 10-K, which is on file with the SEC, and in other filings that we may make with the SEC in the future. Any FLS represents our views as of today only. While we may elect to update 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. Please turn to slide four.
spk14: Good morning. Thank you, Elhan, and thank you all for joining today for CarioFarm'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 a moment. Turning to slide five, 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 multi-myeloma market, including Exposio's growing role pre and post T cell therapies. Additionally, with our partners, we continue to expand Cellinexor's presence, including recent reimbursement decisions in both China and the United Kingdom. Sohani will talk to our commercial performance in the quarter. 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 Cell and XOR in new indications if approved. We continue to believe that Cell and XOR can generate up to 2 billion of annual peak sales in the United States alone, depending on the outcome of our three pivotal phase three data readouts in 2025. As seen on slide six, 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 2028 and 2029, well beyond the expected data readouts and potential approvals of our three phase three 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. Mike will discuss the details of the refinancing later on the call. Moving to slide seven, I would now like to turn the call over to Reshma to expand further on our pipeline and the progress we have made. Reshma?
spk06: Thank you, Richard, and good morning, everyone. On slide 8, you can see our very promising late-stage pipeline with felonexor in three Phase III studies, all of which incorporate felonexor 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-end 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. 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 dostarlimab in combination with chemotherapy, followed by dostarlimab 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. PP53 wild type represents a potentially unique but fundamental biomarker, as it is found in the majority of all advanced recurrent endometrial cancer. As seen on slide 11, patients whose tumors who are both PMMR and p53 wild-type represent 40 to 55% of all advanced or recurrent endometrial cancer patients. The long-term follow-up data from the TP53 wild-type subgroup of the FIENDER trial, which evaluated selenoxor as a 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 treatments. after completion of approximately six 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. These robust subgroup data demonstrate the potential to provide substantial benefit to a unique and sizable population defined by P53 status. which directly ties to Selinexor's mechanism of action, given that XPO1 inhibition retains P53 within the nucleus, thus enhancing cell kill. As shown on slide 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 Selenexor 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 EC042 pivotal phase 3 study, which will enroll approximately 220 women whose tumors are TP53 wild type. We look forward to presenting top-line results from this pivotal trial in the first half of 2025. 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. XPO1 inhibition is a fundamental mechanism in myelofibrosis given that it targets both JAK and non-JAK pathways. underscoring selenexor additive, if not potentially synergistic activity, when dosed in combination. As you can see on slide 17, we presented updated data last year from our trial evaluating selenexor 60 milligrams with ruxolitinib in JAK inhibitor-naive patients. Amongst the 14 patients enrolled to the selenexor 60 milligram dose, a 78% SVR35 at week 24 was observed in the ITT population. Importantly, amongst the evaluable patients, 100% achieved an SVR35 at any time. As we move to slide 18, 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 19, both TSS50 and absolute TSS showed very meaningful improvements at week 24. 58% of the ITT and 78% of the efficacy of valuable achieved a TSS50 response. For absolute TSS, an average 18.5-point improvement was observed in the efficacy-evaluable population at the same time point. Compare these to historical ruxolitinib data, where TSS50 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 Stalinex or 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 selenexor plus ruxolitinib has the potential to maximize symptom improvement relative to ruxolitinib alone in the ongoing Phase III study. The subgroup analysis shown on slide 20, which depicts SCR35 and TSS50 responses, despite treatment with suboptimal doses of ruxolitinib, is suggestive of potential monotherapy activity. To further demonstrate salinexor'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 Century 2 Phase 2 trial, as you see on slide 21. This trial will include treatment-naive myelofibrosis patients with moderate thrombocytopenia and is the potential to entrench Selinexor as a foundational therapy in approximately 90% of 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 III, shown on slide 22, which evaluates the combination of Selinexor 60 milligrams with Bruxolitinib versus Bruxolitinib alone, in 306 JAK-naive myelofibrous patients. We remain on track to report top-line results in the second half of 2025. 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. We have also been hearing encouraging feedback on the positive evolution of Expovio, its effectiveness and tolerability at the lower doses and real-world outcomes observed with its use in combination with the well-established backbone therapy of pomalidomide and dexamethasone. Seen on slide 25, we are evaluating Selenixor at the low dose of 40 milligrams with this combination in our ongoing Phase III 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 Silhanya to review our commercial highlights.
spk05: Thank you, Reshma. Turning now to slide 27, I will discuss our commercial highlights for the first quarter of 2024. In the first quarter, Expovio net product revenue was 26 million, 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 first quarter of the year, adversely impacted Expovio net product revenue this quarter. The community setting contributed to roughly 60% of Expovio's net revenues in the first quarter. 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 Expovio 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. This advantage places Selinexor in a flexible position in the treatment paradigm as a novel mechanism of action. In the first quarter, 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 Expovio's 2024 net product revenue guidance of $100 to $120 million. Now turning to slide 28 and shifting to achievements in the ex-U.S. as Expovio continues to expand its global footprint, we are pleased with the positive recommendation by NICE in the United Kingdom for reimbursement of Selinexor in the early aligned treatment setting. inclusion in China's national reimbursement drug list as of January 1, 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.
spk02: 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 2028 and 2029, well beyond expected data readouts from our three phase three trials and potential launches, positioning Keriopharm for sustainable value creation. Now, I will walk you through the 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 million, or 86% of the 172.5 million existing convertible notes due in 2025 for approximately $111 million of newly issued secured convertible notes due in 2029. This exchange is at a 25% discount to PAR. We now have $24.5 million remaining of the existing convertible bond due in October 2025. In addition, Healthcare Royalty or ACRX purchased $5 million of the 2029 convertible notes. Second, we issued a new $100 million senior secured term loan due in 2028 with $85 million committed from certain existing convertible note holders and $15 million from HCRX. We used $49.5 million of the proceeds along with $5 million in 2029 convertible notes and $15 million 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 HDRX eliminating any potential gross-up payments and reducing the royalty rate on net revenues to 7% down from 12.5%. 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 an additional approximately $30 million of cash strengthens our balance sheet with cash runway into the end of 2025. The confidence and continued support in carrier farm suture from Healthcare Royalty and our top convertible note holders reflects their confidence in the potential of Cellinexor and 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. Total revenue for the first quarter of 2024 was $33.1 million, compared to $38.7 million for the first quarter of 2023. Net product revenue from U.S. commercial sales of Expobio for the first quarter of 2024 was $26 million, compared to $28.3 million for the first quarter of 2023. The gross-to-net discount for Expobio in the first quarter of 2024 was 29%. As a reminder, gross to net are typically higher in the first quarter. We expect gross to net discounts to be in the 25% to 30% range for the full year of 2024. Our total expenses for the first quarter of 2024 were down year-over-year 4%, reflecting our ongoing cost reduction initiatives and focus investments in our late-stage pipeline. R&D expenses for the first quarter of 2024 were $35.4 million, compared to $32.3 million for the first quarter of 2023. The increase in R&D expenses was primarily attributable to higher clinical trial costs related to the advancement of our three pivotal Phase III programs. SG&A expenses for the first quarter of 2024 were $29.5 million, compared to $35.9 million for the first quarter of 2023. The decrease in SG&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, total of $149.3 million, compared to $192.4 million as of December 31, 2023. Next, in 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 to $160 million. ExpovioNet U.S. product revenue expected to be in the range of $100 to $120 million. We are also reaffirming our expense guidance for the full year of 2024 as follows. R&D and SG&A expenses are expected to be in the range of $260 to $280 million. which includes approximately 20 to 25 million of estimated non-cash stock-based compensation expense. And finally, we expect our existing cash, cash equivalent investments, as well as the revenue we expect to generate from ExpovioNet 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 three phase three 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. Richard?
spk14: Thank you, Mike. As you can see on slide 33, we have several key milestones across 24 and 25 and are pleased to have extended the vast majority of our debt maturities into 2028 and 2029. well beyond the data readouts and potential approvals of our three Phase III 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 III clinical trials in multiple myeloma, endometrial cancer, and myelofibrosis, each of which would be transformative for patients and our organizations. 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 saline XOR 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. Thank you again for joining us today, and I would now like to ask the operator to open up the call to the Q&A portion of today's call.
spk08: Operator?
spk07: Thank you. Ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press star followed by the number one on your touchstone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number two. If you are using a speakerphone, please lift the handset before pressing any keys. And your first question comes from the line of Chris Raymond from Piper Sandler. Please go ahead.
spk12: Hey, thanks for taking my question. A couple quick ones here. Just on the refinancing and the amended royalty agreement, so 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. Can you maybe just sort of boil this 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 for Expovio between the sort of academic and community settings. And I think in your prepared comments, you mentioned that gross net spreads this quarter were fairly consistent with what you'd expect in the first quarter. But is there any sort of difference in gross net spreads between the two settings that you can describe?
spk14: Thanks. Yeah, thanks, Chris. As I mentioned, I think a lot of excitement around being able to fundamentally adapt our balance sheet and really strengthen it as we move forward. So For the first part of your question, I'll turn to Mike to really talk about, you know, from a cash perspective and looking at our interest expense.
spk02: 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 two components of interest expense for us. There's our interest on our debt as well as our royalty expense. agreement with HCR, which is recorded through interest expense. So going forward, we expect interest expense this year to be around $18 million for the debt component. So that excludes HCR. 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 million. So if you combine the two together, that's what you'll see.
spk12: Thank you.
spk14: Yeah. 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 to six points. And so when I look at it, I think, you know, it's quite difficult to break it out. It really depends on source of business within each one of those areas versus kind of a general statement across, you know, academic and community.
spk02: Yeah, I just added it. A mix of business is really the key that drives PTN, and I'm usually in Q1 up, so that starts higher in the year. So, you know, we think we'll end up in our range of 25% or 30% with some, you know, volatility each quarter.
spk08: Thank you. Thanks, Chris.
spk07: Your next question comes from the line of Peter Lawson from Barclays. Please go ahead.
spk01: 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, you know, what could we learn from the updated Siendo data at ASCO? You know, what do you think investors should focus on there? And then related, any differences in the patient population, you know, in Siendo compared to the ongoing pivotal study that we should keep in mind? Thank you.
spk14: Yeah, thanks, Alex. For that, I'm going to turn to Raish. I'm going to talk through that.
spk06: Yeah, thanks, Alex, for the great question. So a couple of highlights around ASCO. So first off, you know, it's really an honor from ASCO. We were actually invited to present an update on the P53 wild-type subgroup. 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, you know, 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 saline XOR in this novel population. of p53 wild-type endometrial cancer. So can't go into more details, but really looking forward to this opportunity, and I want to thank Vicki Mocker at MSK for presenting on behalf of all of the investigators. In terms of your second question, so really the, you know, the main differences in this trial relative to Siendo, once again, it's going to be that patient population. So C&O 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. So in Siendo, we treated everybody with a dose of Selenaxor at 80 milligrams weekly. In 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.
spk08: Thanks, Alex.
spk07: Thank you. And your next question comes from the line of Maury Crayford from Jefferies. Please go ahead.
spk03: 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 yet mature. For the data at ASCO in a couple weeks, Can you say if you're going to have an update on PFS in the PMMR group and also on OS for the study? And, yeah, maybe I'll start with that question.
spk06: Yeah, thanks, Maury. Really appreciate the question. 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, you know, we are going to have an opportunity to present, you know, updates on efficacy, so both PFS and then these new analyses, right, so that will, you know, 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.
spk03: Got it. That's helpful. When you speak with doctors about what doctors want to see 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&O? Yeah.
spk06: 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 distarlimab was approved in combination with chemotherapy, followed by distarlimab 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 one. In terms of the actual median overall survival, I think that's going to take some time for it to mature. You know, these patients are living longer and longer. 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.
spk03: Okay. And just to clarify, is there a benchmark or some sort of a landmark in Ciendo on OS that you want to achieve or that doctors would want to see for that study?
spk06: No, not at this time. You know, I think it's very much evolving. So, you know, 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.
spk03: Got it. Okay. And maybe one last question and then I'll hop back in the queue. You said you could have myelofibrosis phase one data update this year. What could that look like and what venue would make sense for that update?
spk06: Yeah, so I think the focus really is going to be on that Century 2 trial. So Century 2, it's a new acronym for the trial, but it is that 0.044 trial that we alluded to at J.P. Morgan. This is that Selenexor monotherapy trial that we're evaluating in the JAK-Naive patient population. That is going to be our focus, you know, for this year. And we anticipate being able to provide some initial preliminary data, both from an efficacy as well as a safety perspective sometime in 2024. You know, with that said, the phase one 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.
spk08: Okay, great. Thanks for taking my questions. Thanks, Maureen.
spk07: And your next question comes from Colleen Cussie from Beard. Please go ahead.
spk04: 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? And then I will follow up.
spk06: Yeah, 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. You know, when we look at the P53 subpopulation, that breakdown of 80-20 is going to be similar to 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% and 20%, very similar to what we are seeing in the natural population.
spk08: Yes. And is that something you're stratifying for?
spk04: What are the items that you're stratifying for in that phase three enrollment?
spk06: 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, selenexor and placebo. So again, not stratifying.
spk04: Understood. Helpful. Thank you. And then in myelofibrosis, I know your ongoing phase three has the co-primary endpoint of both SPR35 and TSS50. Just curious if you've had any recent interactions with the FDA on kind of the role of TSS50 specifically and kind of how you're thinking about the approvable endpoints of myelofibrosis.
spk06: Yeah, 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 two 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 I data, which really suggests that the combination of selenexor plus ruxolitinib can maximize the benefit we see across these two endpoints. It continues to remain that. If you add additional DOR data, it really demonstrates that the patients, once they achieve that SVR35 or TSS50, 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 III trial.
spk04: Great, thank you. And then one commercial question, if I can. So, Hanya, in the pre- and post-T cell therapy setting, can you 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 fourth? Thanks.
spk05: Yeah, absolutely. So, there's several ways that Selinexor can be used pre- and post- as well as peri-T cell therapies. 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? So higher the new patient starts, your higher refills. The good news in Q1, we saw 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 line 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. 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.
spk08: Great. Thanks for taking our questions. Thanks Colleen.
spk07: And your next question comes from the line of Ryan Abrahams from RBC Capital Markets. Please go ahead.
spk11: Hi there. Good morning. Thanks for taking my questions. Two for me. I guess first on the endometrial phase three, I understand the majority of the patients are likely to be PMMR, 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 I'm just wondering if those are still there or if those have been eliminated as well. Thanks.
spk14: Thanks, Brian. Maybe I'll turn to Dr. Raishman to talk to the first part, and then Mike to talk to the second part.
spk06: Thanks, Brian. Great question. You know, 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 two subgroups, they show very meaningful benefits. So in that PMMR, P53 wild-type subgroup, we're seeing a very impressive 0.32 hazard ratio. But when you look at the DMMR patient population, you're also seeing a very strong, you know, 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 going to be about that P53 status. So right now, we really want to leverage that P53 status and determine the patient population based upon that unique biomarker and be able to ultimately drive use across this broad population.
spk14: Yeah, and for the second part, when we look at the updated agreement, so I'll turn to Mike to touch on that point.
spk02: Sure, Brian, you know, and especially, I think, referring to the amended agreement with HCR, so that still stays consistent where, you know, in that case, they do get, you know, their return is capped at 1.95x, so that would stay the same. And as far as the convert, you know, we have customary make-hold provisions in the agreement.
spk08: Thank you. Thanks, Brian.
spk07: Your next question comes from the line of Ed White from H.C. Wainwright. Please go ahead.
spk13: Good morning. Thanks for taking my question. Just one for me. The SGA has trended lower and was just wondering if, you know, with all your cost reductions, are they all in place now? Is the sales force right size now? And are you expecting to see further lower expenses in SG&A or are we sort of at a more stabilized trend? level now. Thanks.
spk14: Yeah, thanks, Ed. I think, as you know, we've had a strong focus on really being very diligent with regards to our capital allocation, reducing, you know, 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, you know, the focus right now is on our late stage pipeline. And we're going to continue that focus. At the same time, you know, our commercialization capability and our commercial team, as we've talked to, is profitable with regard to our multi-myeloma business. You know, right now, you know, driving a two-to-one ROI and really helping to fund our pipeline. So I think we have the right resources in place. And maybe Mike, you want to add some more?
spk02: Yeah, just a little more detail. I mean, I think we've been running right around 30 million, Q3 last year, Q4 last year, Q1 this year, and we expect it to be consistent, you know, going forward.
spk08: Okay, great. Thanks for taking my question. Thanks, Ed.
spk07: And as a reminder, if you wish to ask a question, please press star 1. Your next question comes from the line of Jonathan Chang from Learing Partners. Please go ahead.
spk09: 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 hard level questions for now. One, what are the key implications of these agreements for the equity holder? And two, what is the impact of these agreements on your cash runway guidance? It doesn't seem to have moved that much, but I might be missing something.
spk14: Thank you. Yeah, I think we'll turn to Mike. Maybe, Mike, we start with number two first and then go to number one.
spk02: Sure. Our cash runway guidance is now into the end of 2025. So it was, you know, between the $30 million of cash coming in, you know, our current operating plan, as well as the new interest payments offset by the lower royalty payments, you know, take us into the end of 2025. And then you want to touch on that first part? I'm happy to. So I think overall, the important The 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 exchanged them at a 25% discount so far. You know, from a timing perspective, you know, why now? We wanted to address this, you know, before it becomes current. So, as we've said in the past, we really wanted to address this within 12 to 24 months of maturity, and we're sort of right in the middle of that sweet spot. So, overall, you know, we're pleased to have the vast majority of our data obligations well beyond our expected data readouts and potential approvals.
spk08: Got it. Thanks for taking the questions. Yep. Thanks, Jonathan.
spk07: Thank you. And again, if you wish to ask a question, please press star 1. There are no further questions at this time. And I'd like to hand over the call to Richard Paulson for closing remarks.
spk14: Thank you, operator. And thank you again to everyone today for joining us. You know, 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 with our three Phase III 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. And once again, I want to thank you for joining us today.
spk07: Thank you. Ladies and gentlemen, this concludes today's conference call. You may now disconnect.
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