Q1 2024 Karyopharm Therapeutics Inc Earnings Call

Liz: 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. I would now like to turn the call over to Elhan Webb, Senior Vice President, Investor Relations.

Good morning, My name is listen I'll be your conference operator today at this time I'd like to welcome everyone to the care, you'll find therapeutics first quarter 2024 financial results Conference call.

There will be a question and answer session to follow.

Used to be advised that this call is being recorded at the company's request.

I would now like to turn the call over to Al <unk> Senior Vice President Investor Relations.

Elhan Webb: Thank you, Liza, and thank you all for joining us on today's conference call to discuss Karyopharm'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 of 2024. This release, along with a slide presentation that we will reference during our call today, is available on our website. For today's call, as seen on slide two, I'm joined by Richard, Reshma, Sohanya, and Mike, who will provide an update on our first quarter results and recent financing transactions that we announced this morning as well.

al: Thank you Lisa and thank you all for joining us on today's conference call to discuss the tariff on the first quarter 'twenty 'twenty four financial results and recent company progress.

al: We issued a press release this morning detailing our financial results for the first quarter of 'twenty 'twenty four.

al: It really is along with the slide presentation that we will reference during our call today are available on our website.

Speaker Change: Core to this call as seen on slide two I'm joined by Richard raise your muscle I am Mike who will provide an update on our first quarter results and recent financing transaction that we announced this morning as well.

Elhan Webb: Before we begin our formal comments, I'll remind you that various remarks we will make today constitute Forward-Looking Statements, or FLS, for purposes of the safe harbor provisions under the Private Securities Reduction Reform Act of 1995, as outlined on slide 16. However, actual results may differ materially from those indicated by this 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 Any FLS represents our views as of today only.

Speaker Change: Before we begin our formal comments I'll remind you that various remarks, we'll make today constitute forward looking statements or effortless for purposes of the safe Harbor provisions under the private Securities Litigation Reform Act of 99 to five as outlined on slide three.

Speaker Change: Actual results may differ materially from those indicated by these SLS 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 plywood does he see and in other filings that we may make with the SEC seem to feature and yes. That's it.

Speaker Change: Presenting our views as of today only.

Elhan Webb: 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.

Speaker Change: While we may elect to update these and thought that 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 SLS that'd be presenting our views as of in the later date.

Speaker Change: I will now turn the call over to reach at least talk to slide four.

Richard: Good morning. Thank you, Elhan, 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 a moment.

Rebecca: Good morning, Thank you Alan and thank you all for joining today for carryover arms Q1 2024 earnings call.

Rebecca: 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.

Speaker Change: I'll touch more on this in a moment.

Richard: 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. Reshma will talk about our pipeline program. Commercially, in the United States, we are pleased with the results this quarter in the highly competitive multivitamin market, including Expovio's growing role pre and post T cell therapy. Additionally, with our partners, we continue to expand Cellinex Horse Presence. Including recent reimbursement decisions in both China and the United Kingdom.

Speaker Change: 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.

Speaker Change: Rachel will talk to our pipeline progress.

Speaker Change: Commercially in the United States, we are pleased with our results this quarter in the highly competitive multiple myeloma market, including exposure is growing role premium post T cell therapies.

Speaker Change: Additionally, with our partners, we continue to expand <unk> presence, including recent reimbursement decisions in both China and the United Kingdom, Johnny will talk to our commercial performance in the quarter.

Richard: Sohanya will talk about our commercial performance in the quarter. As we look to the future, the commercial infrastructure that we have built provides us with the capability to support the rapid and smooth commercial launch of Selenexor in new indications, if approved. We continue to believe that Cellinexor can generate up to $2 billion in annual peak sales in the United States alone, depending on the outcome of our three pivotal phase three data readouts in 2025.

Johnny: As we look to the future the commercial infrastructure built provides us with the capability to support the rapid and smooth commercial launch of Selinexor in new indications if approved.

Johnny: We continue to believe that Selinexor can generate up to $2 billion of annual peak sales.

Johnny: The United States alone depending on the outcome of our three pivotal phase III data Readouts in 2025.

Richard: 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 readout.

Johnny: As seen on slide six importantly from a financial perspective, we have taken a significant step that improves our capital structure.

Johnny: Strengthening our opportunity to realize the full value of our late stage pipeline.

Johnny: Our comprehensive refinancing and amended royalty agreement announced this morning extended the vast majority of our debt maturities into 2028 and 2029.

Johnny: Well beyond the expected data readouts and potential approvals of our three phase III programs.

Johnny: Finally through continued disciplined execution in a concentrated pipeline, we have and expect runway into the end of 2025, providing us with the financial strength to deliver on our pivotal data readouts.

Richard: Mike will discuss the details of the refinancing later on in 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. Thank you.

Johnny: Nick will discuss the details of the refinancing later on the call.

Nick: Moving to slide seven I would now like to turn the call over to <unk> to expand further on our pipeline and the progress we have made for Asia.

Reshma: Thank you, Richard. And good morning, everyone.

Nick: Thank you Richard and good morning, everyone on slide eight you can see are very promising late stage pipeline with Selinexor in three phase III studies, all of which incorporate selinexor doses at 40 or 60 milligrams once weekly.

Reshma: On slide 8, you can see our very promising late-stage pipeline with Felinexor in three Phase III studies, all of which incorporate Felinexor 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.

Turning our attention to endometrial cancer on slide 10.

And Dmitry <unk> cancer is a key focus in our pipeline given the high unmet need and substantial benefit observed in patients whose tumors are P 53, wild type advanced and recurrent endometrial cancer is the most common form of gynecologic cancer in the United States with approximately 16000 patients diagnosed each year.

Reshma: 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. TP53 wild type represents a potentially unique but fundamental biomarker as it is found in the majority of all advanced recurrent endometrial cancer.

Nick: All of the treatment landscape is being driven by molecular classifications.

Nick: Today, four D MMR patients, who represent approximately 20% of advanced recurrent endometrial cancer. The new SBA approved standard has just started that in combination with chemotherapy followed by <unk> maintenance.

Nick: And then the <unk>, which represent the remaining 80% of patients the primary treatment options chemotherapy, followed by watching weight. Despite the availability of the checkpoint inhibitors given the limited efficacy achieved with these agents in this molecular subgroup.

Nick: P. P 53, 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 PNM and pizza, particularly wild type represents 40% to 55% of all advanced era.

Reshma: As seen on slide 11, patients whose tumors 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 SIENDA trial, which evaluated Selonexor as a maintenance therapy, have generated substantial enthusiasm from the medical community and highlight Selonexor's potential to meaningfully improve outcomes for patients with With the paradigm shift underway, opinion leaders confirm that there is a clear unmet need for patients whose tumors are P53 wild-type and emphasize the opportunity for new agents.

Nick: Current endometrial cancer patients.

Nick: The long term follow up data from the <unk> 53, a wild type subgroup of the <unk> trial, which evaluated selinexor as a maintenance therapy has generated substantial enthusiasm from the medical community and highlights Selinexor has potential to meaningfully improve outcomes for patients with key pieces between wild type endometrial Ken.

Speaker Change: Sir but.

Speaker Change: But the paradigm shift underway opinion leaders confirm there is a clear unmet need for patients whose tumors are P 53, wild type and emphasize the opportunity for new agents.

Reshma: On slide 12, you can see that long-term follow-up data with Selenexor treatment after completion of approximately six months of chemotherapy showed a median PFS for Selenexor 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 Selenexor's mechanism of action, given that XPO1 inhibition retains P53 within the nucleus, thus enhancing cell kill.

Speaker Change: On Slide 12, you can see this long term follow up data, which saw an extra treatment. After completion of approximately six months of chemotherapy. So the median PFS for selinexor or 27, four months and $5 two months for placebo, a corresponding to a hazard ratio of 0.41.

Speaker Change: Robust subgroup data demonstrate the potential to provide substantial benefit to a unique and sizable population defined by piece of <unk> three status, which directly ties to selinexor. Its mechanism of action given that <unk> inhibition retains P 53 within the nucleus, thus enhancing celtel.

Reshma: As shown on slide 13, the benefit observed with Selenexor 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.

Speaker Change: As shown on slide 13, the benefit observed with Selinexor in the P. MMR subpopulations, even more impressive with a hazard ratio of 0.32 and the median PFS that has not been reached as of our most recent data cutoff presented.

Speaker Change: These efficacy data coupled with a generally manageable side effect profile suggests that oral selinexor is uniquely positioned as an optimal maintenance therapy, where convenience tolerability.

Speaker Change: Meaningful efficacy in a precise patient population are the hallmarks of a maintenance option.

Speaker Change: We look forward to the oral presentation at the Astro meeting in June where additional follow up data and new analyses from this important T. P 53, Wildcat subgroup will be reported.

Reshma: 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. Now, let's move to myelofibrosis.

Speaker Change: On Slide 14, you can see the design of our E. C. O <unk> two pivotal phase III study, which will enroll approximately 220 women, whose tumors are <unk> 53, wild type we look forward to presenting top line results from this pivotal trial in the first half of 2025.

Reshma: 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, xp01 inhibition is a fundamental mechanism in myelofibrosis given that it targets both jack and non-jack pathways, underscoring felinexor additive if not potentially synergistic activity when dosed in combination.

Speaker Change: Let's now move to myelofibrosis.

Speaker Change: As you can see on slide 16, Russell Loopnet remains the standard of care for the majority of JAK naive patients. However, there is an opportunity to improve benefit given the efficacy with <unk>, There's limited with only about 35% of patients achieving an SCR 35 or less than half of those pay.

Speaker Change: <unk>, achieving a meaningful symptom improvement.

Speaker Change: <unk> inhibition is a fundamental mechanism in myelofibrosis, given that it targets the check and non JAK pathways underscoring selinexor additive if not potentially synergistic activity when dosed in combination.

Reshma: As you can see on slide 17, we presented updated data last year from our trial evaluating selenix or 60 milligrams with ruxolitinib in JAK inhibitor naive patients. Amongst the 14 patients enrolled to the Selenexor 60 mg dose, a 78% Svr35 at week 24 was observed in the IPT population. Importantly, amongst the valuable patients, 100% achieved an SVR 35 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 responses at any time.

Speaker Change: As you can see on slide 17, we presented updated data last year from our trial evaluating Selinexor 60 milligrams with <unk> and JAK inhibitor naive patients a.

Speaker Change: Most of the 14 patients enrolled to the solid looks a 60 milligram dose of 78% SCR 35 at week 24 was observed in the ITT population.

Speaker Change: Portly amongst the Evaluable patients, 100% achieved an SCR 35 at any time.

Speaker Change: As we move to slide 18, when we look at SVR 35 in TSS 50, together, we see that 50% of patients experienced both of these responses at week 24, and 75% experienced both SVR 35 in TSS 50 response at any time.

Reshma: 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 of valuable population at the same time point.

Speaker Change: On slide 19, both T. S. That's 15 absolute TSS showed very meaningful improvements at week 24.

Speaker Change: 58% of the ITT and 78% of the efficacy Evaluable achieved TSS 15 response for.

Speaker Change: Absolute TSS and averaged $18 five point improvement was observed efficacy evaluable population at the same time point.

Reshma: 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 Stolenexor combination, and 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 Change: Compare this historical <unk> data for TSS 50 was observed in 42% to 46% of <unk> treated patients.

Speaker Change: Average TSS improvement was 11% to 14 points all symptom domains were substantially improve the selinexor combination and show that pro inflammatory cytokines demonstrated rapid deep and sustained reductions relative to baseline taken.

Speaker Change: Taken together these data validate that the novel combination of Selinexor, plus <unk> has the potential to maximize symptom improvement relative to rux letting them below.

Speaker Change: Ongoing phase III study.

Reshma: 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 Selenexor'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 This trial will include treatment-naive myelofibrosis patients with moderate thrombocytopenia and has the potential to replace Selenexor as a foundational therapy in approximately 90% of treatment-naive myelofibrosis patients.

Speaker Change: The subgroup analysis shown on slide 20, which depicts a <unk> 35 in TSS 50 responses. Despite treatment with suboptimal doses of Rux Loopnet is suggestive of a potential monotherapy activity.

Speaker Change: To further demonstrate solid X was potential fundamental role in myelofibrosis and to build upon the growing data demonstrating monotherapy activity in both treatment naive and Jack expose myelofibrosis patients. We have initiated the century to phase two trial as you see on slide 21. This.

Speaker Change: Trial will include treatment naive myelofibrosis patients with moderate thrombocytopenia and has the potential to infringe selinexor as a foundational therapy and approximately 90% of treatment naive myelofibrosis patients.

Reshma: As the body of our data grows and positively evolves, we see increasing interest from the medical community on the potential of thalanexor in myelofibrosis. We maintain a high level of confidence in our ongoing phase 3, shown on slide 22, which evaluates the combination of Selenix or 60 milligrams with Ruxolitinib versus Ruxolitinib alone in 306 Jack Naive myelofibros We remain on track to report top-line results in the second half of 2025.

Speaker Change: 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 Brookfield Loopnet versus rux letting them alone.

Speaker Change: And 360, JAK naive myelofibrosis patients.

Speaker Change: We remain on track to report topline results in the second half of 2025.

Reshma: 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 Selenexor's role in preserving cytotoxic T-cell function.

Speaker Change: Turning now to multiple myeloma.

Speaker Change: There is a growing need being discussed amongst myeloma thought leaders to identify and incorporate therapies early into a patient's treatment journey, but do not deteriorate a patient's T cell levels in which can be used pre and post T cell redirection therapies, such as bi specifics and car Ts.

Speaker Change: We've been building a body of evidence around selinexor his 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.

Reshma: As seen on slide 24, we are further evaluating the effect of Selenexor 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 lower doses, and real-world outcomes observed with use in combination with a well-established background therapy of pomalidomide and dexamethasone. As seen on slide 25, we are evaluating Selinexor at the low dose of 40 milligrams with this combination in our ongoing phase 3 trial against post-antiperspirant 38 antibodies.

Speaker Change: We have also been hearing encouraging feedback on the positive evolution of exposure. It is.

Speaker Change: Septimus and Tolerability at the lower doses real world outcomes observed with <unk>.

Speaker Change: With the Houston combination with a well established backbone therapy of <unk> and dexamethasone.

Speaker Change: On slide 25, we are evaluating selinexor at the low dose of 40 milligrams with this combination in our ongoing phase III trial post anti CD 38 antibodies, we expect to report topline data from this trial in the first half of 2025.

Sohanya: 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 Sohanya to review our commercial highlights. Thank you, Reshma.

Speaker Change: 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 <unk> to review our commercial highlights.

Sohanya: Turning now to slide 27, I will discuss our commercial highlights for the first quarter of 2024. In the first quarter, Expovio's 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've seen 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.

Speaker Change: Thank you raised turning now to slide 27, I will discuss our commercial highlights for the first quarter of 2024 and.

Speaker Change: In the first quarter exposure net product revenue was 26 million minus 8% year over year, and plus 4% quarter over quarter amid increased competition.

Speaker Change: 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.

Speaker Change: Additionally, our higher gross to net discount typical of what we see in the first quarter of the year adversely impacted <unk> net product revenue this quarter.

Speaker Change: The community setting contributed to roughly 60% of exposing those net revenues in the first quarter.

Sohanya: 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 Exposio continues to fulfill patient needs in an evolving competitive multiple myeloma landscape. As Reshma mentioned, xp01 inhibition provides patients with a potentially T cell sparing treatment option before or after T cell therapy. This advantage places Selenexor 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.

Speaker Change: It 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.

Speaker Change: This is encouraging as new patient starts have the potential to positively impact <unk> net product revenue in upcoming quarters.

Speaker Change: In the academic setting that was quarter over quarter growth in demand as exposure continues to fulfill patient needs.

Speaker Change: Evolving competitive multiple myeloma landscape.

Speaker Change: As <unk> mentioned <unk> inhibition provides patients with a potentially T cell sparing treatment option before or after T cell therapies.

Speaker Change: Advantage places selinexor in a flexible position in the treatment paradigm as a novel mechanism of action.

Speaker Change: In the first quarter expose yields new patient mix in the second to fourth line states.

Speaker Change: Stable quarter over quarter.

Sohanya: As we look ahead, we expect to see continuation of cellinexor 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 therapy. In a highly competitive multiple myeloma landscape, our team is executing with resilience to drive an increasingly important role for telenethor 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.

Speaker Change: As we look ahead, we expect to see continuation of Selinexor treatment in second third and fourth lines, primarily in the community setting and in later lines in the academic setting typically pre or post T cell therapies.

Speaker Change: 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.

Speaker Change: We are reaffirming exposure 2024, net product revenue guidance of $100 million to $120 million.

Sohanya: Now turning to slide 28 and shifting to achievements in the ex-U.S., as Explovio 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 on 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.

Speaker Change: Now turning to slide 28, and shifting to achievements in the ex U S. As <unk> continues to expand its global footprint.

Speaker Change: We're pleased with the positive recommendation by nice in the United Kingdom for reimbursement of Selinexor in the earlier line treatment setting.

Speaker Change: <unk> in China's national reimbursement drug list as of January one 2024.

Speaker Change: <unk> approval for reimbursement in Germany.

Speaker Change: In conclusion, our multiple myeloma franchise continues to positively impact more patients every year, while being a key driver in funding our pipeline.

Sohanya: 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. Good morning, everyone, and

Speaker Change: Our strong commercialization team is focused on expanding our multiple myeloma business and rapidly launching in potential future indications.

Speaker Change: Now I would like to turn the call over to Mike to discuss our recently announced transactions and give an update on our financials.

Mike: 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 so far.

Mike: Good morning, everyone. And thank you, Sohanya. Before turning to our OneQ 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 3 trials and potential launches, positioning Karyopharm 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.

Mike: Good morning, everyone and thank you so on your <unk>.

Mike: Turning to our <unk> 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 III trials and potential launches.

Mike: <unk> carrier for them for sustainable value creation.

Mike: We now have $24.5 million remaining on the existing convertible bond due in October 2025. In addition, Healthcare Royalty, or HERX, 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 HCRX, eliminating any potential gross up payments and reducing the royalty rate on net revenues to 7%, down from 12.5%.

Mike: 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.

Mike: First we retired approximately $148 million or <unk>, 86% of the $172 5 million existing convertible notes due in 2025 for approximately $111 million of newly issued secured convertible notes due in 2020.

Mike: This exchange is at a 25% discount to par.

Mike: We now have $24 5 million remaining of the existing convertible bond due in October 2025.

Mike: In addition, health care royalty or <unk> purchased $5 million of the 2029 convertible notes.

Mike: 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 HRS, we used $49 $5 million of the proceeds along with $5 million in 2021 convertible notes and <unk> 15.

Mike: Of the secured term loan to <unk> to satisfy the remaining principal portion under our existing agreement with HCR X.

Mike: Lastly, we amended our existing agreement with HCR, <unk>, eliminating any potential growth of payments and reducing the royalty rate on net revenues to 7% down from 12, 5%.

Mike: 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. 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 Karyopharm's future from Healthcare Royalty and our top convertible note holders reflects their confidence in the potential of Cellinexor in our late-stage pipeline program.

Mike: Overall, you can see the difference in our debt maturity profile on the right side of the slide.

Mike: Our total liabilities to reduce slightly an additional approximately $30 million of cash strengthens our balance sheet with cash runway into the end of 2025.

Mike: The confidence and continued support carrier farms' future from healthcare royalty and Archrock convertible noteholders reflects their confidence in the potential of Selinexor in our late stage pipeline programs.

Mike: 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 benefits 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.

Mike: These transactions represent a fundamental change in benefit to our capital structure and the financial health of the company.

Mike: <unk>, our opportunity to deliver the value of our late stage pipeline as we provide benefit to patients in need new treatment options.

Mike: Net product revenue from U.S. commercial sales of Expovio 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 Expovio for the first quarter of 2024 was 29%.

Mike: 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.

Mike: Total revenue for the first quarter of 2024, it was $33 4 million compared to $38 7 million for the first quarter of 2023.

Mike: Net product revenue from U S commercial sales of <unk> for the first quarter of 2024 was $26 million.

Mike: Fair to $28 3 million for the first quarter of 2023.

Mike: As a reminder, gross to net is typically higher in the first. We expect gross net discount to be in the 25 to 30% range for the full year 2024. Our total expenses for the first quarter of 2024 were down year over year by 4%, reflecting our ongoing cost reduction initiatives and focused investment, and our Lake 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.

Mike: The gross to net discount for <unk> in the first quarter of 2024 was 29% as a reminder, gross to nets 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 2024.

Mike: Our total expenses for the first quarter of 2024 were down year over year, 4%, reflecting our ongoing cost reduction initiatives and focused investments in our <unk>.

Mike: Late stage pipeline.

Mike: 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 program.

Mike: The increase in R&D expenses is 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.

Mike: 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.

Mike: The decrease in SG&A expenses was primarily due to our ongoing cost reduction initiatives and lower headcount.

Mike: Cash, cash equivalents, restricted cash, and investments as of March 31, 2024 totaled $149.3 million compared to $192.4 million as of December 31, 2023. Nathan, 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 to 160 million, Spovio Net U.S. Product revenue is expected to be in the range of $100 to $120 million. We're 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 expenses.

Mike: Cash cash equivalents restricted cash and investments as of March 31, 2024 totaled $149 3 million compared to $192 4 million as of December 31, 2023 Nathan.

Based on our current operating plans, we are reaffirming revenue guidance for the full year of 2024 as follows total revenue is expected to be in the range of $140 million to $160 million.

Mike: <unk> net U S product revenue expected to be in the range of $100 million to $120 million.

Mike: We're also reaffirming our expense guidance for the full year of 2024. It follows R&D and SG&A expenses are expected to be in the range of $2 $60 million to $280 million, which includes approximately $20 million to $25 million of estimated noncash stock based compensation expense.

Richard: And finally, we expect our existing cash and cash equivalents, as well as the revenue we expect to generate from ExpovioNet product sales and other licensed 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 free 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.

Mike: Finally, we expect our existing cash cash equivalents investments as well as the revenue we expect to generate from exposure net product sales and other license revenues will be sufficient to fund our planned operations into the end of 2025.

Mike: In summary, we have taken significant steps to improve our capital structure with our recent debt exchange an amended agreement with healthcare royalty. We are rapidly advancing our three phase III trials and driving commercial performance, while continuing to be very diligent when allocating our resources.

Mike: Now flip to slide 32, and turn the call over to Richard for some final thoughts Richard.

Richard: 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 three 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.

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.

Mike: 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.

Richard: 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. And we believe the largest opportunities for Salinexor 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 for the Q&A portion of today's call. Operator.

Mike: Each of which would be transformative for patients and our organization.

Mike: 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.

Mike: As we believe the largest opportunities for selinexor are yet to come.

Mike: 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 encourage of patients with cancer and the potential of our novel mechanism of action to positively impact their lives.

Speaker Change: 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 operator.

Operator: 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 touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline 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 key. And your first question comes from the line of Chris Raymond from Piper Sandler. Please go ahead.

Speaker Change: 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 Touchtone phone you will hear from that you had has been raised should you wish to decline from that.

Operator: Ruling process. Please press the star followed by the <unk>.

Operator: You are using a speaker phone please lift the handset before pressing NTT east.

Operator: And your first question comes from the line of Chris Raymond from Piper Sandler. Please go ahead.

Chris Raymond: Hey, thanks for taking my question. Just a couple quick ones here.

Chris Raymond: 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.

Chris Raymond: Just on the refinancing and the amended royalty agreement, so there are 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 us down to what the projected new quarterly interest expense might look like? That's the first question.

Chris Raymond: A description of the you guys have been carrying a pretty consistent interest expense each quarter.

Chris Raymond: Can you, maybe just sort of boils down to what the projected new quarterly interest expense might look like.

Chris Raymond: Then secondly, I know you guys have talked for quite a while about the competitive environment between the 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?

Speaker Change: The first question and then secondly.

Speaker Change: I know you guys have talked for quite a while about the competitive environment between the for exposure between the air.

Speaker Change: Academic and community settings.

Speaker Change: And I think in your prepared comments, you mentioned that gross to net spreads.

Speaker Change: This quarter were fairly consistent with what you would expect in the first quarter, but is there any sort of yeah.

Speaker Change: Difference in gross to net spreads between the two settings that you could describe thanks.

Chris Raymond: Thanks. Yeah, thanks, Chris.

Richard: Yeah, thanks, Chris. As I mentioned, I think there is a lot of excitement around being able to fundamentally change 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 look at our interest expense. Thanks, Richard.

Speaker Change: Yeah. Thanks, Chris.

Speaker Change: As I mentioned, I think a lot of excitement around being able to fundamentally adapt our balance sheet and really strengthen 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. Thanks, Richard Yes at a high level. These transactions certainly strengthen our cash balance and improve our cash run.

Mike: 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, there are two components of interest expense for us. There's our interest on our debt, as well as our royalty 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.

Mike: Into the end of 2025 beyond our expected data Readouts from <unk> 25 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 is our interest on our debt as well as our royalty.

Mike: <unk> 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 ACR agreement to reduce our royalty rate from 12% to 7% so for the rest of.

Mike: So that excludes HCR. And then, 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. Thank you.

Mike: 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.

Mike: 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, 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 really depends on the source of business within each one of those areas versus kind of a general statement across, you know, academic and community.

Speaker Change: Great. Thank you.

Speaker Change: And for the second part Chris when you look at the GTS between the community and the academic I mean overall I think as we've talked to the GTS.

Speaker Change: Is up six points.

Chris Raymond: And so when we look at it I think.

Chris Raymond: Quite difficult to break it out really depends on source of business within each one of those areas.

Chris Raymond: Versus kind of a general statement across academic and community.

Chris Raymond: I would just add book mix of business is really the key that drives TTM unusually in Q1 up so that starts higher in the year. So we think we'll wind up in a range of 25% to 30% with some.

Mike: Yeah, I'll just add a mix of business is really the key that drives P10. And I'm usually in Q1 up, so that starts higher in the year. So, you know, we think we'll end up in that our range of 25 to 30% with some, you know, volatility.

Chris Raymond: Volatility each quarter.

Speaker Change: Thank you.

Speaker Change: Thanks, Chris.

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

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

Alex: Hi, good morning. This is Alex on behalf of Peter.

Speaker Change: Hi, Good morning. This is Alex on for Peter Thank you for taking our questions.

Alex: We have two questions on the endometrial program.

Alex: Thank you for taking our questions. We have two questions on the endometrial program. Just wondering what we could learn from the updated Siendo data at ASCO. What do you think investors should focus on there? And then, related, are there any differences in the patient population in Siendo compared to the ongoing pivotal study that we should keep in mind? Thank you.

Speaker Change: Just wondering if you could.

Speaker Change: What could we learned from the updated <unk> data at <unk>.

Speaker Change: What do you think investors should focus on there.

Speaker Change: And then related.

Speaker Change: Any differences in the patient population.

Speaker Change: Endo compared to the ongoing pivotal study that we should keep in mind. Thank you.

Reshma: Yeah, thanks, Alex. For that, I'm going to turn to Reshma to talk through that. Yeah, thanks, Alex, for the great question.

Speaker Change: Yes, Thanks, Alex.

Speaker Change: I'm going to turn to duration when you talk through that yeah. Thanks, Alex for the great question.

Reshma: 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 on that P53 wild type subgroup.

Speaker Change: So a couple of highlights around <unk>, so first off.

Speaker Change: Really an honor from the IOSCO, we were actually invited to present, an update on the P. 53, Wild type subgroup and this is a follow on from the ASIC a plenary last year I think it resonated with a lot of Kols ESCO again really wanted us to perform an update from that P 53, wild type subgroup.

Speaker Change: So at this upcoming IOSCO, we're going to use this opportunity to really update both efficacy as well as safety.

Reshma: 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 Selenexor and this novel population of P53 wild-type endometrial cancer. So can't go into more details, but really looking forward to this opportunity.

Speaker Change: And provide some new analyses that I think will further highlight the potential benefit risk that we see with solid export and this novel population of P. 53, Wild type endometrial cancers. So can't go into more details, but really looking forward to this opportunity and I want to thank Vicki marker at M. S K for presenting.

Reshma: And I want to thank Vicky Mocker at MSK for presenting on behalf of all of the investigators. In terms of your second question, really, the main differences in this trial relative to Siendo are going to be that patient population. So Siendo enrolled an all-comers population, meaning 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.

Speaker Change: On behalf of all of the investigators.

Speaker Change: In terms of your second question so.

Speaker Change: The you know the main differences in this trial relative to <unk>. Once again, it's going to be that patient population. So <unk> enrolled in all comers population and that all patients with advanced or recurrent endometrial cancer, where potentially eligible to be randomized in the current trial.

Speaker Change: We're just focusing on those patients who have P 53, wild type, which is evaluated by MTS testing with our partner Foundation medicine and the other key difference not necessarily related to the patient population, but an important differences to dose.

Reshma: 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 Selenoxor 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 between the two trials.

Speaker Change: So in <unk>, we treated everybody with a dose of Selinexor 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.

Speaker Change: Thanks, Alex.

Speaker Change: Yes.

Speaker Change: Okay.

Speaker Change: Thank you Anne.

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

Speaker Change: Your next question comes from the line of Martin <unk> from Jefferies. Please go ahead.

Maury: 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 this study? And yeah, maybe I'll start with that.

Martin: Hi, good morning.

Martin: Thanks for taking my question.

Martin: I was going to ask our cause.

Martin: A couple more specifics on the upcoming data at <unk>. So late last year you guys presented some initial OS data at the <unk> Conference and also in your last cut.

Martin: Median PFS in the <unk> group was not yet mature for the data at Ash a couple of weeks.

Martin: Can you say, if youre going to have an update on PFS in the P. M. Our group and also on OS for this study.

Speaker Change: And yes, maybe.

Speaker Change: Maybe I'll start with that question.

Reshma: Yeah, thanks, thanks, Maury. I really appreciate the question. At this point, I can't at this point 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, so that will, you know, provide additional color on the benefit risk. So more to come in the next few weeks, but I'm really excited to be able to provide this update.

Speaker Change: Yeah, I think thanks, Maury I really appreciate the question.

Speaker Change: Can't at this point just provide any additional details in terms of the exact analyses that were going to present.

Speaker Change: Keep in mind again, you know we are going to have an opportunity to present updates on efficacy. So both PFS.

Speaker Change: And then this new analyses right. 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.

Maury: Got it. That's helpful. And when you speak with doctors about what doctors want to see as an 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?

Speaker Change: Got it that's helpful.

Speaker Change: When you speak with doctors about what doctors want to see.

Speaker Change: On OS what's the landmark OS that you want to achieve in this study and.

Speaker Change: Also can you talk about some of the drivers of AUM that you're you're focused on <unk>.

Reshma: Yeah, so the trial is powered to detect a meaningful and statistical difference in terms of PFS, so progression-free survival, very similar to the Sando trial and very similar to the endpoints for which distalimab was approved in combination with chemotherapy, followed by distalimab 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.

Speaker Change: Yeah. So.

Speaker Change: The trial is powered to detect a meaningful and statistical difference in terms of PFS or progression free survival very similar to the <unk> trial and very similar to the endpoints in which <unk> was approved in combination with chemotherapy followed by the starlet by maintenance specifically in that DMA.

Speaker Change: Ah patient population. So the focus is very much going to be on PFS with that said <unk> is a key secondary endpoint and the goal is to really show no detriment at the time of the primary cut off and we define no detriment, specifically by a hazard ratio of less than one.

Reshma: In terms of the actual median overall survival, I think that's going to take some time for that data to mature. You know, 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 with future updates.

Speaker Change: In terms of the actual median overall survival I think that's going to take some time for it to mature or you know these patients are living longer and longer and well continue to follow that overall survival and as that data matures from this ongoing trial will be able to provide those additional data at future with future update.

Maury: 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 Change: <unk>.

Speaker Change: Okay, and just to clarify is there a benchmark or some sort of a landmark and see endo on OS that that you want to achieve or that doctors would want to see.

Speaker Change: For that study.

Reshma: No, not at this time. You know, 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 Change: No no not at this time.

Speaker Change: You know I think it's very much of all things. So you know at this point I don't have a landmark to be able to provide them again I think the focus very much is the no detriment that I mentioned earlier.

Maury: You said you could have a myelofibrosis Phase 1 data update this year. What could that look like, and what venue would make sense for that update?

Speaker Change: Got it Okay and then maybe one last question and then I'll hop back in the queue.

Speaker Change: You said you could have myelofibrosis phase one data update this year, what could that look like and what venue would make sense for for that update.

Reshma: Yeah, so I think the focus really is going to be on that CENTRI2 trial. CENTRI2, 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 the Selenexor monotherapy trial that we're evaluating in the Jack 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.

Speaker Change: Yeah. So I think the focus really is going to be on that century, two trials with century to it's a it's a new acronym for the trial, but it is that 0.0 44 trial that we alluded to at J P. Morgan on this is that Selinexor monotherapy trial that we're evaluating in the JAK naive patient.

Speaker Change: Population that is going to be our focus for this year.

Speaker Change: And do we anticipate being able to provide some initial preliminary data both from an efficacy as well as the safety perspective sometime in 2024.

Reshma: You know, with that said, the phase one Selenexor ruxolitinib trial is still ongoing as well, and we'll be able to provide some additional updates, both in efficacy and safety, later this year as well. Okay, great. Thanks.

Speaker Change: With that said the phase one <unk> trial is still ongoing as well and we'll be able to provide some additional updates both an efficacy and safety perspective later this year as well.

Maury: Okay, great. Thanks for taking my question.

Speaker Change: Okay, great. Thanks for taking my questions.

Speaker Change: Thanks Laurie.

Operator: And your next question comes from Colleen Kusy from BEARD. Please go ahead.

Speaker Change: And your next question comes from Choline Kathy from Baird. Please go ahead.

Speaker Change: Sure.

Colleen Margaret Kusy: Great. Good morning.

Speaker Change: Yeah.

Colleen Margaret Kusy: Great. Good morning, Thanks for taking our questions and congrats on the refinancing.

Colleen Margaret Kusy: Thanks for taking our questions, and congrats on the refinancing. One, on the endometrial Phase III, how do you expect the enrollment in the Phase III will be split among the PMMR and DMMR patients? And what are the characteristics you're stratifying for, and would that include MMMR status? And then I have a follow-up. Yeah, great.

Colleen Margaret Kusy: One on net the endometrial phase III, how do you expect enrollment in the phase III will be split among the P MMR and DMR patients and what are.

Colleen Margaret Kusy: The characteristics are stratified for and would that include MMR animal Maher status and then I have a follow up.

Reshma: Yeah, a 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 those with P-MMR. They comprise approximately 80% of all patients. When we look at the remaining population, or 20%, they're going to be in that D-MMR patient population. You know, when we look at the P53 subpopulation, that breakdown of 80-20 is going to be similar within that P53 wild-type subgroup.

Speaker Change: Yeah, Great question and thank you Colleen.

Speaker Change: So when we look at the endometrial cancer patient population and specifically MMR. The vast majority of patients are going to be that Pete MMR. They comprise approximately 80% of all patients. When we look at the remaining population of 20%, they're going to be in that DMR patient population.

Speaker Change: When we look at the P 53, subpopulation that breakdown of 80 20 is going to be similar.

Reshma: If I had to anticipate the proportion of patients who are D-MMR 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.

Speaker Change: Within that within that pay 53, wild type subgroup, if I have to anticipate the proportion of patients who are D. MMR 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.

Speaker Change: Yeah.

Speaker Change: Okay.

Reshma: And is that something you're stratifying for? What are the items that you're stratifying for in that PACE re-enrollment? We're not stratifying.

Speaker Change: And is that something you stratify inquiry or what are the items that you start to think we're at that phase three enrollment we're not stratified yes. Thank you for that follow up so we're not strive defying based upon MMR status. So again, because we assume that the majority of patients are going to be P. MMR, we assume that there's going to be a similar split across the two.

Reshma: We're not stratifying. Yes, thank you for that follow up.

Colleen Margaret Kusy: 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, we aren't stratifying.

Speaker Change: Two arms Selinexor and placebo.

Speaker Change: Again not stratify.

Colleen Margaret Kusy: And then in myelofibrosis, I know your ongoing phase three has the co-primary endpoint of both SBR35 and TSS50. Just curious if you've had any recent interactions with the FDA on the role of TSS50 specifically and kind of how you're thinking about the approvable endpoints for myelofibrosis.

Speaker Change: Understood helpful. Thank you and then in Myelofibrosis I know your ongoing phase III has the co primary end point of both SPR thirty-five at TSS 50, just curious have you had any recent interactions with the FDA I'm kind of the role of GSS 50, specifically and kind of how youre thinking about the approvable endpoints in myelofibrosis.

Reshma: Yeah, so we don't comment on the specifics of our FDA interactions. You know, 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%.

Speaker Change: Yeah. So we don't comment on the specifics with our FDA interactions.

Speaker Change: With that said I think in the myelofibrosis space. The focus has always been and continues to be on two main endpoints. This is gonna be SVR 35, 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 one.

Reshma: So we're very much focused on those endpoints and very encouraged by our phase one data, which really suggests that the combination of Selenexor plus Ruxolitinib can maximize the benefit we see across these two endpoints. However, 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 I am really encouraged by the compilation of data, and I think it just provides further confidence in the potential outcomes for our phase three trial.

Speaker Change: Data, which really suggests that the combination of Selinexor plus rux I'll, let Ned can maximize the benefit we see across these two endpoints.

Speaker Change: <unk> to remain that if you add additional DLR data it really demonstrates that the patients once they achieve that SVR 35, or TSS 50 remain in dose responses. So really encouraged by the compilation of data and I think it just provides further confidence in the potential outcomes for our phase <unk>.

Speaker Change: Ah trial.

Sohanya: And then one commercial question, if I can. Sohanya, 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.

Speaker Change: Great. Thank you and then one commercial question if I can.

Speaker Change: In the pre and post T cell therapy, setting can you speak to the type of duration of treatment you are seeing in that patient population versus what you see on average in the second to third line setting or is that going to four things.

Sohanya: Yeah, absolutely. So there are several ways that Selenexor can be used pre and post, as well as during T cell therapy. In the pre stage, it can be used as a shorter bridge, which could be, you know, one cycle, or it can be used as a unique line of therapy preceding T cell therapy, which could be several months long. Now, as you look at the different puts and takes of duration of therapy, there are a couple of key drivers.

Speaker Change: Yeah, absolutely so.

Speaker Change: There are several ways that somebody makes or can be used pre and post as well as Perry T cell therapies.

Speaker Change: It can in the pre stage it can be used as a shorter bridge, which could be you know 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.

Sohanya: One is the new patient start volume, right? So the higher the new patient starts, your higher refills. The good news is that in Q1, we saw really nice growth versus the prior quarter in new patient starts in the academic setting, as well as in 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.

Speaker Change: There's a couple of key drivers one is the new patient start volume right. So no higher than new patient starts you hire of 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.

Speaker Change: Area around duration of therapy, how long patients stay on therapy that is really driven by a couple of different factors. One is what lines of therapy. They are they are on earlier line patients stay on therapy longer that's typically in the community as well as we've got the offset our balance in the academic setting that.

Sohanya: Earlier lines, patients stay on therapy longer, that's typically in the community, as well as in the academic setting, where we see 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.

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

Colleen Margaret Kusy: and Post T-Cell Therapy Space. Great, thanks for taking our questions.

Speaker Change: Great. Thanks for taking our questions.

Speaker Change: Thanks Colin.

Operator: And your next question comes from the line of Ryan Abrahams from RBC Capital Markets. Please go ahead.

Speaker Change: And your next question comes from the line of Ryan <unk> from RBC capital markets. Please go ahead.

Unknown Attendee: Hi there. Good morning. Thanks for taking my questions. Two for me.

Ryan: Hi, there good morning, Thanks for taking my questions. Two from me I guess first on the endometrial phase III.

Unknown Attendee: I guess first, on 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.

Ryan: I understand the majority of the patients are likely to be <unk>, 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 PMO population would there be any reason not to do that.

Ryan: 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 and in that situation and I'm. Just wondering if those are still there or if those have been eliminated as well. Thanks.

Richard: Thanks, Brian. Maybe I'll turn to Duresh when I talk to the first part and then Mike to talk to the second part.

Speaker Change: Thanks, Brian maybe I'll turn to duration when I talked to the first part and then Mike to talk to the second part.

Reshma: Yeah, thanks, Brian. A great question.

Duration: Yeah, Thanks, Brian Great question.

Duration: One of the reasons that.

Reshma: 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.

Duration: We're focusing on both the <unk> as well as the DMR patient populations is because if you look at the hazard ratio.

Mike: Across the two subgroups they shows very meaningful benefit so when that TMR pizza three wall type subgroup were seeing a very impressive three.

Mike: <unk> two hazard ratio, but when you look at the TMR patient population.

Mike: So seeing a very strong you know approximately point for 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 thriving or predicting the benefit. It's all it's going to be about that P. 53 status. So right now we really.

Reshma: 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 again going to be about that P53 status. So, you know, 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. Yeah, and for the second part, when I look at the updated agreements.

Mike: We want to leverage that piece of the three status and determined the patient population based upon that unique biomarker.

Mike: And be able to ultimately drive use across this broad population.

Reshma: Yeah, and for the second part, we're going to look at the updated agreement, so I'll turn to Mike to touch on that point. Sure, Brian, 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 is concerned, you know, we have customary make-hold provisions in the agreement.

Mike: For the second part when you look at the updated agreement. So I will turn to Mike to touch on that point sure Bryan, especially referring to the amended agreement with HCR. So thats still stays consistent where in that case do you get.

Mike: The return is capped at 195 extra that would that would you.

Mike: Stay the same and as far as the convert we have customary make whole provisions in the agreement.

Mike: Thank you.

Mike: Thanks, Brian.

Mike: Your next question comes from the line of Ed White from HC Wainwright. Please go ahead.

Mike: Your next question comes from the line of Ed White from each Wainright. Please go ahead.

Operator: Good morning. Thanks for taking my question. Just one for me.

Unknown Attendee: Good morning, Thanks for taking my question.

Unknown Attendee: Just one for me.

Unknown Attendee: Okay.

Unknown Attendee: The SGA has trended lower, and I was just wondering if, you know, with all your cost reductions, are they all in place now? Is the sales force the right size now? And are you expecting to see further lower expenses in SG&A, or are we sort of at a more stabilized level now? Thanks.

Unknown Attendee: It's trended lower and was just wondering if you know with all your cost reductions are they all in place now as the sales force right sized now and are you expecting to see further lower expenses and SG&A or are we sort of at a more stabilized level level now.

Unknown Attendee: <unk>.

Richard: Yeah, thanks, Ed. I think, as you know, we've had a strong focus on being very diligent with regard to our capital allocation, reducing headcount, and being very focused on 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 that the focus right now is on our late stage pipeline.

Speaker Change: Yes, Thanks, Ed I think as you know we've got a strong focus on really.

Speaker Change: Being very diligent with regards to our capital allocation, reducing head count 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.

Unknown Attendee: And we don't see.

Mike: And we're going to continue that focus. At the same time, our commercialization capability and our commercial team, as we've talked about, are profitable with regard to our multi-myoma business. Right now, they are 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 can go on and add some more. Yeah, just a little more detail. I mean, I think we've been running right around 30 million, Q3 last year, Q4 last year, and Q1 this year. And we expect it to be consistent going forward.

Unknown Attendee: <unk> right now is on our late stage pipeline.

Unknown Attendee: And we're going to continue that focus at the same time, our commercialization capability and our commercial team.

Unknown Attendee: As we've talked to is profitable with regard terminal to myeloma business right now driving a two to one ROI and really helping to fund our pipeline. So I think we have the right resources in place.

Speaker Change: And maybe it might go on to add 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 going forward.

Speaker Change: Okay.

Unknown Attendee: Okay, great. Thanks for taking my question. Thank you. Thank you.

Speaker Change: Okay, great. Thanks for taking my question.

Speaker Change: Thanks, Ed.

Operator: And as a reminder, if you wish to ask a question, please press star one. Your next question comes from the line of Jonathan Chang from Lear Inc. Partners. Please go ahead.

Speaker Change: And as a reminder, if you wish to ask a question. Please press star one.

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

Jonathan Chang: Hi, guys. Good morning, and thanks for taking my questions.

Jonathan Chang: Hi, guys. Good morning, and thanks for taking my questions.

Jonathan Chang: We're still working through the math on the refinancing agreements and amendments announced this morning, so just a couple higher-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. Thank you.

Jonathan Chang: We're still working through the math on the refinancing agreements and amendments announced this morning.

Jonathan Chang: So just a couple high level questions for now.

Jonathan Chang: One what are the key implications of these agreements with the equity holder.

Jonathan Chang: And two what is the impact of these agreements on your cash runway guidance it.

Speaker Change: It doesn't seem to have moved that much but I might be missing something thank you.

Mike: Yeah, I think we'll turn to Mike, maybe Mike, we start with number two first and then go to number one. Sure, our cash run guidance is now into the end of 2025. So it was, you know, between the $30 million of cash coming in based on our current operating plan, as well as the new interest payments offset by the lower royalty payments that will take us into the end of 2025. And then you want to touch on that first part. I'm happy to oblige.

Speaker Change: Yes, I think I'll turn to Mike maybe we start with number two first and then go to number one.

Mike: Sure our cash runway guidance is now on to the end of 2025.

Mike: Between the $30 million of cash coming in.

Mike: Based on our current operating plan as well as the new interest payments offset by the lower royalty payments will take us into the end of 2025, and then you went.

Speaker Change: To touch on the first part.

Mike: So I think overall, the important thing here for equity holders is, you know, there's a lot of excitement around our phase three program. So we want to strengthen our balance sheet to unlock value by extending the maturity of our debt obligation well beyond our planned data readouts and potential approval. So we took advantage of the Convert trading at a discount and exchanged them for them at a 25% discount to PAR. From a timing perspective, you know, why now? We wanted to address this before it becomes current.

Speaker Change: I'm happy to so I think overall the important thing here for equity holders is and there's a lot of excitement around our phase III 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 at this.

Speaker Change: And exchange them at a 25% discount to par.

Speaker Change: From a timing perspective, you know why now we wanted to address this before the before it becomes current so as we've said in the past we really wanted to address this within 12 to 24 months maturity and we're sort of Reagan.

Mike: 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 approval.

Speaker Change: In the middle of that sweet spot so overall.

Speaker Change: We were pleased to have the vast majority of our debt obligations well beyond our expected data readouts and potential approvals.

Jonathan Chang: Got it. Thanks for taking the question. Yep. Thanks, John.

Speaker Change: Got it thanks for taking the questions.

Speaker Change: Yes, thanks, Jonathan.

Operator: Thank you. And again, if you wish to ask a question, please press star one. There are no further questions at this time, and I'd like to hand over the call to Richard Paulson for closing remarks.

Speaker Change: Thank you and again, if you wish to ask a question. Please press star one.

Speaker Change: There are no further questions at this time.

Speaker Change: And I'd like to hand over to Carl to Richard Paulson for closing remarks.

Richard A. Paulson: Thank you, operator. And thank you again to everyone today for joining us.

Carl: Thank you operator, and thank you again to everyone today for joining us as we really highlighted on the call.

Richard A. Paulson: You know, as we really highlighted on the call, we are 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 three phase three clinical trials. We've touched on the fact that each one of them would be transformative for patients, you know, 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.

Carl: Very pleased with the substantial improvement in our capital structure, we have strengthened our opportunity to realize the full value of our late stage pipeline and with our three phase III clinical trials.

Carl: And we've touched on the fact that each one of them would be transformative for patients and transformative for organization. So we're continuing to be focused on delivering our next stage of growth and once again want to thank you for joining us today.

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

Speaker Change: Thank you ladies and gentlemen. This concludes today's conference call you may now disconnect.

Carl: [music].

Carl: Yes.

Carl: Okay.