Q4 2023 Karyopharm Therapeutics Inc Earnings Call

Ludi: Good morning. My name is Ludi, and I will be your conference operator today. At this time, I would like to welcome everyone to the Karyopharm Therapeutics 4th Quarter and Full Year 2023 Financial Results Conference Call. There will be a question and answer session following. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Elhan Webb, Senior Vice President of Investor Relations. Please go ahead.

Good morning, My name is Judy and that will be a conference operator today.

Judy: This time I would like to welcome everyone to the car you fine Therapeutics fourth quarter and full year 2020 financial results Conference call.

There'll be a question and answer session to follow.

Judy: Please be advised that this call is being recorded at the company's request.

Judy: I would now like to turn the call over to Al <unk> Senior Vice President of Investor Relations. Please go ahead.

Elhan Webb: Thank you, Ludi, and thank you all for joining us on today's conference call to discuss our financial results and recent company progress. We issued a press release this morning detailing our financial results for the fourth quarter and full year 2020. 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 results for the fourth quarter and full year 2023 and recent clinical development. Before we begin our formal comments, I'll remind you that the various remarks we'll make today constitute forward-looking statements, FLAs, for purposes of the Safe Harbor Provision under the Privacy Security Dedication Reform Act of 1995, as outlined on slide 16.

al: Thank you Lucy and thank you all for joining us on today's conference call to discuss the financial results and recent company progress we issued a press release. This morning detailing our financial results for the fourth quarter and full year 2023.

al: This release, along with a slide presentation that we will let's just doing our call today are available on our website.

Speaker Change: For today's call as seen on slide two I'm joined by Richard raised muscle Han Yun, Mike who will provide an update on our results for the fourth quarter and full year 2023, and recent clinical developments.

Speaker Change: Before we begin our formal comments I'll remind you that various remarks, we'll make today constitute forward looking statements for purposes of the safe Harbor provisions under the private Securities Litigation Reform Act of 1995.

Speaker Change: Outlined on slide three.

Elhan Webb: Actual results may differ materially from those indicated by the FLS as a result of various important factors, including those discussed in the risk factors section of our most recent form 10-Q or 10-K, which are on file with the SEC, and in other filings that we may make with the SEC in the future. Any FLS represents our views as of today. While we may elect to update these efforts 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 as representing our views as an emulator. I will now turn the call over to Richard. Please turn to slide four. Good morning.

Speaker Change: Actual results may differ materially from those indicated by these F. L. A as a result of various important factors, including those discussed in the risk factors section of our most recent Form 10-Q, our 10-K, which are on file with the FCC and in other filings that we may make with the SEC seem to feature.

Speaker Change: Any F L X it presents our views as of today only.

Speaker Change: While we may elect to update these 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 specialists as representing our views at the annual later date.

Speaker Change: I'll now turn the call over to Richard Please turn to slide four.

Richard: Good morning, Thank you Anne and thank you for joining us today for carrier farms Q4, and full year 2023 earnings call My.

Richard A. Paulson: Thank you, Elhan. And thank you for joining us today for Karyopharm's Q4 and full year 2023 earnings call. My name is Richard Paulson, President and Chief Executive Officer of Karyopharm.

Richard Dalton: My name is Richard Dalton, President and Chief Executive Officer Cary Apart.

Richard A. Paulson: As you can see on slide five, over the past few years, we have been intently focused on positioning ourselves for our next stage of growth with three late-stage trials, supported by a growing body of unprecedented data in both solid and hematological malignancies that are expected to read out next year. The data we are seeing in myelofibrosis and endometrial cancer are highly encouraging, and we believe the largest opportunities for Selenexor are yet to come. These trials will potentially enhance and create new standards of care for patients and provide significant value creation opportunities in the near term. It is our top priority to advance this eight-stage pipeline, address patients' unmet needs, and, if approved, rapidly expand Salinexor's use in new indications. We are doing this by concentrating our investments in these pivotal programs and leveraging our existing multiple myeloma franchise anchored by our commercial drug Expovio, which is approved in over 40 countries. Generating brand profitability and growing experience with physicians.

Richard Dalton: As you can see on slide five over the past few years, we have been intensely focused on positioning ourselves for our next stage of growth with three late stage trials supported by a growing body of unprecedented data in both solid and Hematological malignancies that are expected.

Richard Dalton: To read out next year.

Richard Dalton: The data we are seeing in myelofibrosis in endometrial cancer are highly encouraging and we believe the largest opportunities for selinexor are yet to come.

Richard Dalton: These trials will potentially enhance and create new standards of care for patients and provide significant value creation opportunities in the near term it.

Richard Dalton: It is our top priority to advance this late stage pipeline address patients' unmet needs and if approved rapidly expand selinexor is used and new indications.

Richard Dalton: We are doing this by concentrating our investments into these pivotal programs and leveraging our existing multi myeloma franchise anchored on our commercial drug exposure.

Richard Dalton: Which is approved in over 40 countries.

Richard Dalton: Generating branded profitability and growing experience with physicians.

Richard A. Paulson: Through ongoing discipline and expense management, we have an expected cash runaway into late 2025, providing us with the financial strength to deliver on key data readouts from our three phase three studies. In 2023, we delivered total revenues of $146 million, meeting our guidance for the full year. And in 2024, we expect to generate $140 to $160 million in total revenues.

Richard Dalton: Through ongoing disciplined expense management, we have an expected cash runway into late 2025.

Richard Dalton: Providing us with the financial strength to deliver on key data readouts from our three phase III studies.

In 2023, we delivered total revenues of 146 million meeting our guidance for full year and in 2024, we expect to generate $140 million to $160 million in total revenues.

Richard A. Paulson: This range reflects the highly competitive nature of the multimile market, with important new entrants in the second half of 2023 and more anticipated this year, which we are mindful of, especially when setting expectations for our financial performance this year. This is balanced by the resilience we have demonstrated and our focus on both near-term and long-term growth. Importantly, our existing commercial infrastructure is profitable today and provides us with the capability to support the rapid and smooth commercial launch of 7XOR in new indications. We are committed to delivering on the opportunities ahead of us and believe Selenexort could generate approximately $2 billion of peak annual revenues in the U.S. alone. And turning now to slide six, let's review some key accomplishments from our core programs in 23, which strengthen our confidence in our ongoing phase three trials.

Richard Dalton: This range reflects the highly competitive nature of the multiple myeloma market with important new entrance in the second half of 2023 and more anticipated this year.

Richard Dalton: Mindful of especially when setting expectations for our financial performance this year.

This is balanced by the resilience, we have demonstrated and our focus on both near term and long term growth.

Richard Dalton: Importantly, our existing commercial infrastructure is profitable today and provides us with the capability to support the rapid and smooth commercial launch of Selinexor in new indications.

Richard Dalton: We are committed to delivering on the opportunities ahead of us and believe selinexor could generate approximately $2 billion of peak annual revenues in the U S alone.

Richard Dalton: And turning now to slide six let's review some key accomplishments from our core programs in 'twenty three.

Strengthen our confidence in our ongoing phase III trials.

Richard A. Paulson: In myofibrosis, we are very encouraged by the comprehensive profile, including tolerability, Spleen Volume Reduction, Symptom Improvement as measured by TSS50, and the long-term durability that we saw in our Phase 1 data of Selenexor plus Ruxolitinib in JAK-naive patients presented at ASH. In endometrial cancer, we are excited by the substantial improvement in medium progression pre-survival for patients who are TP53 wild-type, as reported in the ASCO planetary series.

Richard Dalton: In myelofibrosis, we are very encouraged by the comprehensive profile, including Tolerability.

<unk> volume reduction.

Richard Dalton: Symptom improvement as measured by TSS 50, and a long term durability that we saw in our phase one data of Selinexor plus rux and.

Richard Dalton: In JAK naive patients presented at Ash.

Richard Dalton: And endometrial cancer, we're excited by the substantial improvement in medium progression free survival for patients who are <unk> 53, a wild type <unk>.

Richard Dalton: <unk> reported that the co primary series.

Richard A. Paulson: This highlights the opportunity we may have to deliver unprecedented outcomes for a large and unique population of patients. In multiple myeloma, despite increased competition in the academic setting, we continued to grow expovial in the community setting and shifted its use to earlier lines of treatment. We look forward to the results from our Phase 3 trial, evaluating Salinexor at the low dose of 40 mg in combination with the well-established backbone therapy of pomalidomide and dexamethasone post-anti-C238 antibodies. Turning now to slide seven, as we work to create new standards of care, we expect each of our ongoing phase 3 clinical trials will read out top line results in 2025. Any one of these programs, if approved, represents an incredibly meaningful growth opportunity for our company, with endometrial cancer and myofibrosis representing the largest opportunities. Moving to slide eight, I would now like to turn the call over to Reshma to expand further on our clinical pipeline progress. Reshma.

Richard Dalton: This highlights the opportunity we may have to deliver unprecedented outcomes for a large and unique population of patients.

Richard Dalton: And multiple myeloma despite increased competition in the academic setting we continued to grow <unk> in the community setting and shifted its used to earlier lines of treatment.

Richard Dalton: We look forward to the results from our phase III trial evaluating selinexor at the low dose of 40 milligrams in combination with the well established backbone therapy of panels.

Richard Dalton: And dexamethasone post anti <unk> eight antibodies.

Richard Dalton: Turning now to slide seven as we work to create new standards of care, we expect each of our ongoing phase III clinical trials will read out top line results in 2025.

Richard Dalton: Any one of these programs if approved represents an incredibly meaningful growth opportunity for our company.

Richard Dalton: With endometrial cancer, and myelofibrosis, representing the largest opportunities.

Richard Dalton: Moving to slide eight I would now like to turn the call over duration to expand further on our clinical pipeline progress.

Richard Dalton: Yes.

Reshma Rangwala: Thank you, Richard, and good morning, everyone. As Richard mentioned, on slide 9, we have a very promising late-stage pipeline with Selenexor in three phase 3 studies, all of which incorporate Selenexor doses at 40 or 60 milligrams once weekly. Let's now turn our attention to myelofibrosis on slide 11. Ruxolitinib remains the standard of care for the majority of JAK-naive patients. However, there is an opportunity to improve benefit given that the efficacy of Ruxolitinib is limited, with only about 35% of patients achieving an SVR35, and less than half of all patients achieving meaningful symptom improvement. XPO1 inhibition is a fundamental mechanism in myelofibrosis, given that it targets both JAK and non-JAK pathways.

Duration: Thank you Richard and good morning, everyone as Richard mentioned on Slide nine we have a 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.

Speaker Change: Let's now turn our attention to myelofibrosis on slide 11.

Speaker Change: <unk> 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 Brookfield Loopnet is limited.

Speaker Change: Only about 35% of patients achieving an SCR 35, and less than half of all patients achieving meaningful symptom improvement.

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

Reshma Rangwala: Underscoring selinexor's additive activity is not potentially synergistic activity when dosed in combination, we are evaluating the potential for selinexor in combination with ruxolitinib to provide benefit across all of the hallmarks of the disease, including spleen reduction, symptom improvement, disease modification, and stabilization if not improvement of the cytopenia. As you can see on slide 12, we presented updated data last year from our trial evaluating Selenexor 60 milligrams with rexalitinib in JAK inhibitor-naive patients, which showed an SVR35 of 79% at week 24 in the intent-to-treat population. Importantly, amongst the evaluable patients, 100% achieved an SVR35 at any time. On slide 13, both TSS50 and AbsoluteTSS showed very meaningful improvements at week 24. 58% of the intent to treat and 78% of the efficacy of valuable achieved the TSS50 response. For absolute TSS, an average 18.5 point improvement was observed in the efficacy of the valuable population at the same time point.

Speaker Change: To provide benefit across all of the hallmarks of the disease, including spleen reduction symptom improvement disease modification and stabilization if not improvement of the Cytopenia is.

Speaker Change: As you can see on slide 12, we presented updated data last year from our trial evaluating Selinexor 60 milligrams of <unk> and JAK inhibitor naive patients, which showed an SCR 35 at 79% at week 24 in the intent to treat population.

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

Speaker Change: On slide 13 boats TSS 50 in absolute TSS, so very meaningful improvements at week 24, 58% of the intent to treat and 78% of the efficacy of valuable achieved the TSS 50, a response.

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

Reshma Rangwala: Compared to historical ruxolitinib data, where TSS50 was observed in 42 to 46 percent of ruxolitinib-treated patients, and the average TSS improvement was 11 to 14 points, on slide 14, we see that all symptom domains are substantially improved with the Selenexor combination, with all domains achieving an approximately 50% or greater improvement compared to baseline. The absolute TSS, TSS50, and individual domain improvements are corroborated by cytokine data that show that the pro-inflammatory cytokines, which lead to myelofibrosis symptom development, show rapid, deep, and sustained reductions relative to baseline.

Speaker Change: Compared these two historical <unk> data, where TFS 50 was observed in 42% to 46% of <unk> treated patients and the average TSS improvement with 11% to 14 points.

Speaker Change: Moreover, on slide 14, we see that all symptom domains are substantially improved with the Selinexor combination with all domains, achieving an approximately 50% or greater improvement compared to baseline.

Speaker Change: Absolute PSS PFS 50, and individual domain improvements are corroborated by cytokine data, which showed that the pro inflammatory cytokines, which lead to myelofibrosis symptom development, so rapid deep and sustained reductions relative to baseline taken.

Reshma Rangwala: Taken together, the data demonstrate that the novel combination of selinexor plus ruxolitinib has the potential to maximize symptom improvement relative to ruxolitinib alone in the ongoing phase 3 study. As shown on slide 15, we find the durability data from the Selenexor-Ruxolitinib combination very important for patients. As of the most recent data cutoff, none of the week 24 SVR35 responders dosed at Selenexor 60 milligrams had observed radiographic progressions, and none of the week 24 TSS50 responders had observed symptom progressions.

Speaker Change: Taken together the data demonstrate that the novel combination of Selinexor plus <unk> has the potential.

Speaker Change: Pencil to maximize symptom improvement relative to rock solid nib alone in the ongoing phase III study.

Speaker Change: Shown on slide 15, we filed the durability data from the Selinexor are rock solid and the combination is very important for patients as of the most recent data cutoff. None of the week 24, SVR 35 responders dose that Selinexor 60 milligrams had observed radiographic progression and none of the week 24.

Speaker Change: For TSS 50, responders had observed symptom progressions, while I acknowledge the apparent limitations and cross trial comparisons contrast, these data to <unk> alone in which only approximately 70% of responses were ongoing at 78 weeks.

Reshma Rangwala: While I acknowledge the apparent limitations in cross-trial comparisons, contrast these data to Ruxolitinib alone, in which only approximately 70% of responses were ongoing at 78 weeks. As we move to slide 16, when we look at SVR-35 and TSS-50 together, we see that 50% of patients experienced both of these responses at week 24, and 75% experienced both SVR-35 and TSS-50 responses at any time. On slide 17, we see that in addition to the cytokine data, we also observed signs of disease modification with the stabilization of hemoglobin levels of patients on solanexor 60 milligrams in combination with ruxolitinib. This trend is unique with the solanexor combination, given that with ruxolitinib alone, hemoglobin levels drop after treatment initiation and tend to stay low.

Speaker Change: As we move to slide 16, 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 SPR 35 in TSS 50 response at any time.

Speaker Change: On slide 17, we see that in addition to the cytokine data. We also observed signs of disease modification with the stabilization of the hemoglobin levels of patients on Selinexor 60 milligrams in combination with <unk> <unk>.

Speaker Change: Trend is unique with the Selinexor combination given that with <unk> alone.

Speaker Change: Hemoglobin levels drop after treatment initiation and tend to stay low.

Reshma Rangwala: On slide 18, prominent myelofibrosis leaders in the field are impressed with the profile this unique cell and exer combination may provide to Jack Naive myelofibrosis patients. In fact, one of the most prominent opinion leaders and the principal investigator of the Selenexor plus Ruxelitinib Phase 3 study, Dr. John Mascarenhas, noted that the combination is tolerable and that the spleen and symptom data observed to date from the Phase 1 study may significantly improve these outcomes in first-line myelofibrosis. As the body of data grows and positively evolves, we maintain a high level of confidence in the ongoing phase three study shown on slide 19, which is evaluating the combination of Selenexor 60 milligrams with Ruxolitinib versus Ruxolitinib alone in 306 jack naive myelofibrosis patients.

Speaker Change: On slide 18 prominent in myelofibrosis leaders in the field are impressed with the profile of this unique selinexor combination may provide JAK naive myelofibrosis patients.

Speaker Change: In fact, one of the most prominent opinion leaders and the principal investigator of the Selinexor plus <unk> phase III study Dr. John Mascarenhas noted that the combination is tolerable and the spleen and symptom data observed to date from the phase one study may significantly improve these outcomes in first line myelofibrosis.

Speaker Change: This is.

Speaker Change: As the body of data grow and positively evolve we maintain a high level of confidence in the ongoing phase III study is shown on slide 19, which is evaluating the combination of Selinexor 60 milligrams with <unk> versus <unk> alone in 360, JAK naive myelofibrosis patients.

Reshma Rangwala: We are on track to report top-line results in the second half of 2025. Now, turning now to endometrial cancer. As seen on slide 21, there is a paradigm shift underway for the treatment of women with advanced or recurrent endometrial cancer, the most common form of gynecologic cancer in the United States, with increasing use of molecular classification. TP53 wild type represents a potentially unique but fundamental biomarker in endometrial cancer.

Speaker Change: We are on track to report top line results in the second half of 2025.

Speaker Change: Turning now to endometrial cancer.

Speaker Change: As seen on slide 21, there is a paradigm shift underway for the treatment of women with advanced recurrent endometrial cancer. The most common form of gynecologic cancer in the United States with increasing use of molecular classification.

Speaker Change: P. P 53, wild type represents a potentially unique but fundamental biomarker endometrial cancer.

Reshma Rangwala: 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, checkpoint inhibitors are not approved. As such, the primary treatment option is chemotherapy followed by watch and wait. Patients whose tumors are both PMMR and P53 wild-type represent 40 to 55 percent of all advanced or recurrent endometrial cancer patients.

Speaker Change: Today for D MMR patients, who represent approximately 20% of advanced recurrent endometrial cancer.

Speaker Change: <unk> approved standard is just starlet mab in combination with chemotherapy followed by the start of the Mab maintenance for key MMR, which represent the remaining 80% of patients checkpoint inhibitors are not approved as such the primary treatment option is chemotherapy, followed by watch and wait.

Speaker Change: Patients, whose tumors are both PNM and P 53, wild type represent 40% to 55% of all advanced recurrent endometrial cancer patients.

Reshma Rangwala: As you can see on slide 22, long-term follow-up from the TP53 wild-type subgroup from the CIENDA trial, which evaluated Selenexor as a maintenance therapy and thus after completion of approximately six months of chemotherapy, shows 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 cellinexor's mechanism of action, given that XPO1 inhibition retains P53 within the nucleus, thus enhancing cell kill. As shown on slide 23, the benefit observed with Selenexor in the PMMR subpopulation is even more impressive, with a hazard ratio of 0.32 and a median PSS that was not reached as of our most recent data cutoff.

Speaker Change: As you can see on slide 22 long term follow up from the T. P 53, wild type subgroup from the <unk> trial, which evaluated selinexor as a maintenance therapy and thus after completion of approximately six months of chemotherapy showed the median PFS for Selinexor of 27 four months.

Speaker Change: And five two months for placebo corresponding to a hazard ratio of 0.41.

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

Speaker Change: Kill.

Speaker Change: As shown on slide 23, the benefit observed with Selinexor into P. MMR subpopulation is even more impressive what the hazard ratio of 0.32, and a median PFS that was not reached as of our most recent data cutoff.

Reshma Rangwala: The preliminary overall survival is encouraging, with a hazard ratio of 0.76 observed in all patients with TP53 wild-type and a hazard ratio of 0.57 in the subgroup of patients that are P53 wild-type and PMMR. These efficacy data, coupled with the generally manageable side effect profiles, suggest that oral Selenexor is uniquely positioned as an optimal maintenance therapy where convenience, tolerability, and meaningful efficacy are the hallmarks of a maintenance option.

Speaker Change: The preliminary overall survival is encouraging with a hazard ratio of 0.76 observed in all patients with T. P 53 of wild type and hazard ratio of 0.57 in the subgroup of patients that are P 53, wild type and TMR.

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

Reshma Rangwala: In fact, some of our patients are now reaching their fourth year on therapy. I'm excited to present additional follow-up data later this year. On slide 24, you can see the design of our EC042 Pivotal Phase 3 study, which will enroll approximately 220 women whose tumors are PP53 wild-type. We look forward to presenting top-line results in the first half of 2025. Turning now to multiple myeloma, as seen on slide 26, we are expanding our multiple myeloma franchise with the ongoing phase three trial that is evaluating Selenexor at the low dose of 40 milligrams in combination with the well-established backbone therapy of pomalidomide and dexamethasone, post-anti-CD38 antibodies, which will drive earlier use. We are enrolling patients with relapsed refractory multiple myeloma who have received an anti-CD38 antibody as their most recent therapy. As we are seeing positively evolving data with longer median CFS observed with Selenexor 40 milligrams in combination with pomalidomide and dexamethasone, a beneficial outcome for these patients.

Speaker Change: Back to some of our patients are now reaching their fourth year on therapy I'm excited to present additional follow up data later this year.

Speaker Change: On Slide 24, you can see the design of our U C O <unk> pivotal phase III study, which will enroll approximately 220 women, whose tumors are P. P 53, wild type we look forward to presenting top line results in the first half of 2025.

Speaker Change: Turning now to multiple myeloma.

Speaker Change: On slide 26, we are expanding our multiple myeloma franchise with the ongoing phase III trial that is evaluating selinexor at the low dose of 40 milligrams in combination with the well established backbone therapy of Palmer <unk> Dexamethasone post anti CD 38, antibodies, which will drive earlier use.

Speaker Change: We are enrolling patients with relapsed refractory multiple myeloma, who have received an anti CD 38 antibody is their most recent therapy.

Speaker Change: We are seeing positively evolving data with longer median PFS observed with Selinexor 40 milligrams in combination with <unk> and dexamethasone a beneficial outcome for these patients topline data are now expected in the first half of 2025.

Reshma Rangwala: Top-line data are now expected in the first half of 2025. In summary, we have near-term, late-stage opportunities supported by compelling data in our rapidly advancing pipeline that will potentially benefit multiple cancer patient populations of high unmet need, building on our approved indication. With that, I will now hand it over to Sohanya to review our commercial highlights. Turning now to slide 28 and our commercial highlights for the fourth quarter and full year 2023. In 2023, we achieved 112 million Expovio Net Revenue, meeting our guidance for the year. In the fourth quarter of 2023, Expovio Net Revenues were $25 million.

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 on our approved indications with that I will now hand, it over to <unk> to review our commercial highlights.

Speaker Change: Turning now to slide 28, and our commercial highlights for the fourth quarter and full year of 2023.

Speaker Change: In 2023, we achieved a $112 million <unk> net revenue meeting our guidance for the year in the fourth quarter 2023 exposure net revenues were $25 million.

Sohanya Cheng: During 2023, we achieved total demand growth in the community setting and shifted patient mix into earlier lines consistent with our strategy. We increased our breadth of use, growing our community prescribing sites of care by approximately 20% year over year. The community setting now represents two-thirds of our business and is where the large majority of early-aligned patients are treated. In Q4 2023, Expovio's new patient share was approaching 70% in the second to fourth lines, representing double-digit growth year over year. This shift in mix of patients continues to drive higher refills as early aligned patients tend to stay on therapy longer. We faced some considerable headwinds in 2023, including increased competition from new entrants in the bi-specific class in the later lines, which adversely impacted demand in the academic setting in the second half of 2023. Additionally, higher gross-to-net driven by increased 340B discounts and Medicaid rebates due to the Inflation Reduction Act and a significant increase in free drug or patient assistance program utilization due to closures of multiple myeloma foundations adversely impacted our revenue.

Speaker Change: During 2023, we achieved total demand growth in the community setting and shift the patient mix into earlier lines consistent with our strategy, we increased our breadth of us growing our community prescribing sites of care by approximately 20% year over year.

Speaker Change: Community setting now represents two thirds of our business and is where the large majority of earlier line patients are treated.

Speaker Change: In Q4, 2023 exposure new patient share was approaching 70% in the second to fourth lines, representing double digit growth year over year.

Speaker Change: This shift in mix of patients continues to drive higher refills as earlier line patients tend to stay on therapy longer.

Speaker Change: We faced some considerable headwinds in 2023, including increased competition from new entrants in the bi specific class in the later lines, which adversely impacted demand in the academic setting in the second half of 2023.

Speaker Change: Additionally, higher gross to net driven by increased 340, <unk> discounts and Medicaid rebates due to the inflation reduction act and a significant increase in the free drug or patient assistance program utilization due to closures of multiple myeloma foundation's adversely impacted our revenue.

Sohanya Cheng: In 2023, PAP contributed to 10% of total demand versus 5% in 2022, resulting in roughly a $6 million impact in 2023. As we turn to 2024, we are working to grow our multiple myeloma business versus last year and are guiding to a U.S. Expovio net product revenue range of $100 to $120 million. We believe our guidance range reflects a balance of conviction in our near-term growth strategy for Expovio while also recognizing the increasingly competitive nature of the myeloma landscape. For Expovio, we remain focused on growth in three key areas. First, the community setting.

Speaker Change: In 2023 pop contributed 10% of total demand versus 5% in 2022, resulting in roughly a $6 million impact in 2023.

Speaker Change: As we turn to 2024, we are working to grow our multiple myeloma business versus last year and are guiding to a U S exposure net product revenue range of $100 million to $120 million.

We believe our guidance range reflects a balance of conviction in our near term growth strategy for <unk>.

Speaker Change: While also recognizing the increasingly competitive nature of the myeloma landscape.

Speaker Change: Our exposure, we remain focused on growth in three key areas.

Speaker Change: First the community setting this is where a majority of physicians tend to treat earlier line patients and are looking for agents that are effective manageable and convenient we believe that as Dar select use expands in the frontline, particularly in the community setting it opens up new opportunities for <unk>.

Sohanya Cheng: This is where a majority of physicians tend to treat early-aligned patients and are looking for agents that are effective, manageable, and convenient. We believe that as Darzalec use expands on the front line, particularly in the community setting, it opens up new opportunities for Expovio on the second or fourth line. This is strengthened by our new data and elevation of selinexor in the MPCM guidelines. Second, earlier lines of therapy. We will remain focused on further shifting the use of felinexor into earlier lines of therapy where we see the benefit of increasing the duration of therapy. Third, self-examination. We plan to further build on the evidence around the effectiveness of Expovio pre- and post-T cell redirecting therapy, enabling a flexible position for Selinexor in the treatment paradigm as a novel mechanism of action.

Speaker Change: <unk> in the second to fourth lines.

Speaker Change: This is strengthened by our new data an elevation of selinexor in the Mtc and guidelines.

Speaker Change: Second earlier lines of therapy, we will remain focused on further shifting the use of selinexor into earlier lines of therapy, where we see the benefit of increasing duration of therapy.

Speaker Change: Third T cell fitness, we plan to further build on the evidence around the effectiveness of exposure.

Speaker Change: <unk> and post T cell redirecting therapies, enabling a flexible position for selinexor in the treatment paradigm as a novel mechanism of action.

Sohanya Cheng: As we look to the future of a multiple myeloma franchise, we believe that as a profitable business, generating a two-to-one ROI, it will continue to provide a steady inflow of cash to fuel our pipeline and continue to drive confidence and experience in our product at a lower dose as we prepare for future launches, including the potential approval of the all-oral SPD regimen, which could unlock further growth. Our story in multiple myeloma has been one of resilience and steadfastness in a highly competitive and rapidly evolving environment where the disease remains incurable, and Expovio continues to be an effective option for many patients. Finally, a commercial organization is well established and has developed deep relationships in the community, which represents a key overlapping customer base in both myelofibrosis and endometrial cancer to enable rapid launches in these areas. Now I would like to turn the call over to Mike to give an update on our finances. Good morning, everyone.

Speaker Change: As we look to the future of multiple myeloma franchise, we believe that as a profitable business generating a two to one ROI. It will continue to provide a steady inflow of cash to fuel our pipeline and continue to drive confidence and experience in our product at a lower dose.

Speaker Change: As we prepare for future launches, including the potential approval of the all oral SPD regimen, which could unlock further growth.

Speaker Change: Our story multiple myeloma has been one of resilience and steadfastness in a highly competitive and rapidly evolving environment, whether disease remains incurable and exposure continues to be an effective option for many patients.

Speaker Change: Finally, our commercial organization is well established and has developed deep relationships in the community, which represents a key overlapping customer base in both myelofibrosis and endometrial cancer to enable rapid launches in these areas.

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

Mike: Good morning, everyone and thank you so turning to our financials since we issued a press release earlier today with the full financial results I will just focus on the highlights which begin on slide 13 total revenue for the fourth quarter of 2023 was $33 7 million.

Mike: And thank you, Sohanya. Turning to our financials, since we issued a press release earlier today with the full financial results, I will just focus on the highlights, which begin on slide 30. Total revenue for the fourth quarter of 2023 was $33.7 million, similar to total revenue in the fourth quarter of 2022. Total revenue for the full year 2023 was $146 million, compared to $157.1 million for the full year 2022. Net product revenue from U.S. commercial sales of Expovio for the fourth quarter of 2023 was $25.1 million, compared to $31.1 million for the fourth quarter of 2022. Net product revenue from US commercial sales of Expovio for the full year 2022 was $112 million, compared to $120.4 million for the full year 2022.

Mike: Similar to total revenue in the fourth quarter of 2022 total revenue for the full year 2023 was $146 million compared to $157 1 million for the full year of 2022 net product revenue from U S. Commercial sales of <unk> for the fourth quarter of 2023 was $25 1 million compared.

Mike: With $31 1 million for the fourth quarter of 2022.

Mike: Net product revenue from U S commercial sales of <unk> for the full year 2022 was $112 million compared to $120 4 billion for the full year of 2022.

Mike: The growth to net discount for Expovio in the fourth quarter of 2023 was 23.5%, and for the full year 2023, it was 22%. We expect the growth to net discount to be in the 25 to 30% range for the full year 2024. And as seen in previous years, it is expected to be at the higher end of the range for Q1. R&D expenses for the fourth quarter of 2023 were $39.4 million compared to $30.9 million for the fourth quarter of 2022 and $138.8 million for the full year of 2023 compared to $148.7 million for the full year of 2022.

Mike: The gross to net discount for <unk> in the fourth quarter of 2023 was 23, 5% and for the full year 2023 was 22%.

Mike: We expect the gross to net discount to be in the 25% to 30% range for the full year 2024, and as seen in previous years. It is expected to be at the higher end of the range for Q1.

Mike: R&D expenses for the fourth quarter of 2023 were $39 4 million compared to $30 9 million for the fourth quarter of 2022.

Mike: $138 8 million for the full year of 2023 compared to $148 7 million for the full year of 2022.

Mike: The decrease in R&D expenses was primarily attributable to the decrease in personnel costs as a result of the reduction in headcount in line with the prioritization of our late-stage clinical pipeline and decrease in severance-related expenses. However, these decreases were partially offset by an increase in clinical trial and related costs, primarily due to the advancement of our three pivotal phase three studies, which is expected to slightly increase our R&D expenses in 20 SG&A expenses for the fourth quarter of 2023 were $30.7 million compared to $34.6 million for the fourth quarter of 2022. SG&A expenses for the full year 2023 were $131.9 million compared to $145.4 million for the full year 2022.

Mike: The decrease in R&D expenses was primarily attributable to the decrease in personnel costs as a result of the reduction in head count in line with our prioritization of our late stage clinical pipeline and decrease in severance related expenses.

Mike: These decreases were partially offset by an increase in clinical trial and related costs, primarily due to the advancement of our three pivotal phase III studies.

Mike: Which is expected to slightly increase our R&D expenses in 2024.

SG&A expenses for the fourth quarter of 2023, or $30 7 million compared to $34 6 million for the fourth quarter of 2022.

Mike: SG&A expenses for the full year 2023 were $331 9 million compared to $145 4 million for the full year 2022.

Mike: A decrease in SG&A expenses in 2023 compared to 2022 was due to a decrease in stock-based compensation because of severance-related expenses incurred in 2022. In 2024, we expect our SG&A expenses to slightly decrease as we continue to see the benefits of our cost optimization effort. On a non-GAAP basis, which excludes stock-based compensation, our total R&D and SG&A expenses in 2023 were $249.3 million, in line with our guidance for the year. Cash, cash equivalents, restricted cash, and investments as of December 31, 2023 totaled $192.4 million compared to $279.7 million as of December 31, 2022.

Mike: The decrease in SG&A expenses in 2023 compared to 2022 were due to a decrease in stock based compensation because of severance related expenses incurred in 2022.

Mike: In 2024, we expect our SG&A expenses to slightly decrease as we continue to see the benefits of our cost optimization efforts.

Mike: On a non-GAAP basis, which excludes stock based compensation, our total R&D and SG&A expenses in 2023 or $249 3 million in line with our guidance for the year.

Mike: Cash cash equivalents restricted cash and investments as of December 31, 2023 totaled $192 4 million compared to $279 7 million as of December 31, 2022.

Mike: Based on our current operating plans, we are expecting total revenue of $140 to $160 million for 2024, consisting of the US Expovio net product revenue and license, royalty, and milestone revenue expected to be earned from our partners, primarily Manarini and Antigena. We expect US Expovio net product revenue of $100 to $120 million. R&D and SG&A expenses are expected to be in the range of $260 to $280 million for the full year of 2024, including expected stock-based compensation expense of $20 to $25 million.

Mike: Based on our current operating plans we are expecting.

Mike: Total revenue of $140 million to $160 million for 2024, consisting of U S exposure net product revenue and license royalty and milestone revenue expected to be earned from our partners, primarily mentoring and entergy.

Mike: We expect U S exposure net product revenue of $100 million to $120 million.

Mike: R&D and SG&A expenses to be in the range of $260 million to $280 million for the full year of 2024, including expected stock based compensation expense of $20 million to $25 million.

Mike: And finally, that our existing cash, cash equivalents, and investments, as well as the revenue we expect to generate from Expovio net product sales and other licensed revenues, will be sufficient to fund our planned operations into late 2025. In summary, we continue to be very diligent in the allocation of our resources, and looking at our projected 2024 expenses, we see the results of our pipeline prioritization and headcount reductions over the past couple of years. We are rapidly advancing our three phase three trials and driving our commercial performance while keeping overall expense growth minimal. I'll now flip to slide 31 and turn the call over to Richard for some final thoughts. Richard.

Mike: And finally that our existing cash cash equivalents and 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 late 2025.

Mike: In summary, we continue to be very diligent and allocation of our resources and looking at our projected 2020 for expenses, we see the results of our pipeline prioritization and head count reductions over the past couple of years.

Mike: We are rapidly advancing our three phase III trials and driving our commercial performance, while keeping overall expense growth minimal.

Mike: I'll now flip to slide 31, and turn the call over to Richard for some final thoughts Richard.

Richard A. Paulson: Thank you, Mike. As you can see on slide 32, we're excited about our innovation and growth strategy with our phase three clinical trials in multiple myeloma, endometrial cancer, and myofibrosis, each of which would be transformative for patients and our organization. As I mentioned at the start of the call, we believe the largest opportunities for Cellinexor are yet to come. With data expected from these three phase three trials next year, it's going to be an incredibly exciting time for our organization. We are focused on delivering on our next phase of growth as our people continue to strive each day for patients with high unmet needs, working to generate value for patients and shareholders. Thank you again for joining us today. And I would now like to ask the operator to open the call up to the Q&A portion of today's call. Operator?

Richard Dalton: Thank you Mike as you can see on slide 32, we are excited about our innovation and growth strategy with our phase III clinical trials in multiple myeloma endometrial cancer and myelofibrosis, each of which would be transformative for patients and our organization.

Richard Dalton: As I mentioned at the start of the call. We believe the largest opportunities for selinexor are yet to come.

Richard Dalton: With data expected from these three phase III trials next year is it going to be an incredibly exciting time for our organization.

We are focused on delivering on our next phase of growth as our people continue to strive each day for patients with high unmet needs and working to generate value for patients and shareholders.

Speaker Change: Thank you again for joining us today, and I would now like to ask the operator to open the call up to the Q&A portion of today's call operator.

Operator: Thank you. And, ladies and gentlemen, we will now begin the question and answer session. Should you have a question, please press the star followed by the number one on your telephone keypad. You will hear a prompt as if your hand has been raised. Should you wish to decline the polling process, please press the star followed by the number two. And if you're using a speaker phone, please keep the handset before pressing any keys.

Speaker Change: Thank you and ladies and gentlemen, we will now begin the question and answer session should you have a question. Please press the star followed by the number one on your telephone keypad you will hear from like your hand, that's been raised should you wish to decline from the polling process. Please press the star followed by the number two and if youre using.

Speaker Change: A speaker phone please keep the handset before pressing any key one moment. Please for your first question.

Operator: One moment please for your first question. And your first question comes from the line of Peter Lawson from Barclays. Your line is open. Great. Thank you so much. Do we have questions for Mike or Sohanya just around? Any way to kind of quantify the community? Kind of what you think that looks like.

Speaker Change: And your first question comes from the line of Peter Lawson from Barclays. Your line is open.

Peter Richard Lawson: Great. Thanks, so much.

Peter Richard Lawson: Maybe a question for Mike So just around.

Peter Richard Lawson: If there's any way to kind of quantify the community versus academic setting growth.

Peter Richard Lawson: <unk> III.

Peter Richard Lawson: Kind of what that you think that looks like.

Unknown Executive: Yeah, thanks, Peter, for the question. And you know, when I look overall, I think it's on you to talk to during our prepared comment. You really need to differentiate the environment between the community setting and the academic setting, and I'll turn to Sohanya to kind of elaborate on that, looking at 23 into 24.

Peter Richard Lawson: Exiting the year and into 2024.

Yes, Thanks, Peter for the question I think when I look overall I think I saw in your talk to during our prepared comments.

Speaker Change: You really need to differentiate the environment between the community setting and academic setting and I'll turn Tucson to kind of elaborate on that looking at 'twenty three into 'twenty four.

Sohanya Cheng: Thanks, Peter, for the question. In 2023, as we take a step back, despite the rapid evolution in the competitive landscape, we did achieve total demand growth year over year in 2023 in the community setting. This is an area of hyper-focus for us and a clear growth driver for us in 2024. Another key accomplishment in the community for us in 2023 was that we really broadened our sites of care. So, we now have a broad base of prescribers. We have increased our prescriber base by about 20% year over year.

Tucson: Thank you Peter for the question in 2023, as we take a step back.

Tucson: The rapid evolution in the competitive landscape, we did achieve total demand growth year over year in 2023 in the community setting. This is an area of hyper focus for us and a clear growth driver for us in 2024.

Tucson: Another key accomplishment in the community for Us in 2020 threes, we've really broadened our sites of care. So we now have a broad base of prescribers, we increased our prescriber base by about 20% year over year that is an area, where we want to drive depth in the community in 2024 again.

Sohanya Cheng: That is an area where we want to drive depth in the community in 2024. Again, this is the largest contributor to our business. It's about two-thirds of our business.

Tucson: This is the largest contributor of our business. It's about two thirds of our business switching to the academic setting that contributes to about a third of our business and this is where we see.

Sohanya Cheng: Switching to the academic setting, that contributes to about a third of our business, and this is where we see a rapid evolution of the competitive landscape. So last year, we were really in the eye of the storm, especially in the second half of the year, where we saw downward demand pressure as a result of the uptake of the bi-specific class. Two of the three bi-specifics launched in the second half of last year. Now, as we move into 2024, we do see a couple of new dynamics come into play, potential approval of a fourth bispecific, and potential shifts of CAR T's into earlier lines. However, in terms of defending our business in the academic setting, it's really around enabling a flexible position for Selenexor as a novel mechanism that's easily combinable and supported by our T cell fitness data. So that allows us to really play in the potential pre and post T cell. Therapy space in the academic setting.

Sohanya Cheng: Thank you. And then just, contacted BCMA therapists. Do you think that kind of continues through 24 if you've seen a kind of, major shift already? Yeah, so the bi-specifics, you know, as I touched on, really posed a significant competitive threat in the academic setting, particularly in the second half of last year. As I mentioned, two of the three launched in the second half.

Tucson: Perfect. Thank you and then just the impact of <unk> do you think that.

Tucson: Gotta continues through 24 have you seen kind of the <unk>.

Tucson: A major shift already kind of happened.

Speaker Change: Yeah. So so the bite specifics you know as I touched on a really posed a significant competitive threat in the academic setting, particularly in the second half of last year as I mentioned two of the three launched in the second half now we haven't seen that that up.

Sohanya Cheng: Now, we haven't seen that uptake in the community. We think, you know, that there will be minimal impact in the near term in the community, but in the academic setting, we definitely saw impact. Now, in the real world, we are seeing that these patients are on bi-specific for about eight to nine months. Many are progressing, so it's not a curable option.

Speaker Change: Taken the community. We think you know that's that's going to be minimal impact in the near term in the community, but in the academic setting we definitely saw impact now in real World. We are seeing that these patients are on dice specifics for about eight to nine months. Many are progressing so it's it's it's not.

Speaker Change: Terrible option as we think about the role of Selinexor relative to the by specifics we have published data on positive outcomes post B C. M. A failures. So that really allows us to position ourselves after a by specific and in many cases pre bys.

Sohanya Cheng: As we think about the role of Selenexol relative to the bi-specifics, we have published data on positive outcomes post-BCMA failures, so that really allows us to position ourselves after a bi-specific, and in many cases, pre-bi-specifics as well. Thank you so much, Jim. Thanks, Peter. Thank you. And your next question comes from the line of Maury Raycroft from Japan. Your line is open.

Speaker Change: Specifics as well.

Speaker Change: Alright, thank you so much <unk>.

Speaker Change: Thanks, Peter <unk>.

And your next question comes from the lineup Merry way crop Punjab Police your line is open.

Reshma Rangwala: Hi, good morning, and thanks for taking my questions. I was going to ask one or two about myelofibrosis. I was wondering what your thoughts are on the recent acquisition of Morphosis and what read-throughs there would be to Karyopharm based on how the regulatory process could play out, particularly on the TSS endpoint, which was their key secondary but is your co-primary endpoint. And could you potentially have further conversations with FDA prior to filing and or change the study design if need be? Thanks, Maury.

Merry: Hi, good morning, and thanks for taking my questions I was gonna ask one or two of myelofibrosis wondering what your thoughts are on the recent acquisition of Morphoses and what Readthroughs there would be two carrier farm based on how the regulatory process could play out, particularly on the T. S. S N.

Merry: Which was their queue secondary but as your co primary unemployed.

Merry: And could you potentially have for their conversations would that be a prior to filing in her cage. The study design if need be.

Richard A. Paulson: I'll take the first part of that, and then I'll turn it over to Reshma to take the second part of that. You know, I think when you look at the Novartis and Morphosis acquisition, I think it really validates the high unmet need in the myofibrosis space and really talks to the value of the opportunity for myofibrosis. So, you know, I think that's a strong validation of the value and the unmet need in myofibrosis. And I'll turn to Reshma to talk about, you know, what we're looking at in terms of evolution. And I think we're really in a strong opportunity to watch the evolution of space as it moves forward. Yeah, exactly.

Speaker Change: Thanks for right now I'll take the first part of that and then I'll I'll turn it over to the duration wanted to take the second part of that.

Speaker Change: I think when you look at the.

Speaker Change: Artist more process acquisition.

Speaker Change: Validates the high unmet need in the myelofibrosis space and really talks to the value of the opportunity of myelofibrosis. So.

Speaker Change: That's a strong validation of the the value and the unmet need in myelofibrosis.

Duration: And I'll turn duration better talk about you know what we're looking at in terms of the evolution and I think we're really in a strong opportunity to watch the evolution of the space as as it moves forward.

Speaker Change: Yeah, exactly and thank you for the question Maury.

Reshma Rangwala: And thank you for the question, Maury. You know, I think what we presented today really just outlines the strength that we have across the entire profile of Selenex or Ruxolitinib, specifically the optimal spleen volume reduction, the symptom improvement, right? Not only from a TSS50 perspective, but also now from an absolute TSS50.

Speaker Change: You know I think what we presented today really just outlines the strength that we have across the entire profile of Selinexor ruxolitinib, specifically the optimal spleen volume reduction the symptom improvement right not only from a T. S has 50 perspective, but also now.

Speaker Change: <unk>. That's 50, we further looked at you know individual domains seeing maximum effect across each of the individual domains too and all of that is of course underscored by the side of <unk> data, so really our wealth and growing you know sort of data sat around that symptom score that really suggests that we can maximize benefit <unk>.

Reshma Rangwala: We further looked at, you know, individual domains, seeing maximal effect across each of the individual domains, too. And all of that is, of course, underscored by the cytokine data. So, really, a wealth and growing sort of data set around that symptom score that really suggests that we can maximize benefit across both of those endpoints. Let's not forget disease modification.

<unk> both of those end points, let's not forget disease modification, and then of course improvement and stabilization of the side opinion. So again really just emphasizing that we have the totality profile that is going to be optimal for this Jack naive patient population were very incurred.

Reshma Rangwala: And then, of course, improvement and stabilization of the cytopenia. So, again, really just emphasizing that we have the overall profile that is going to be optimal for this JAK-naive patient population. We're very encouraged, and we're very confident that when we look at symptoms in our Phase 3, it will show meaningful benefit compared to Selenexor alone. As Richard mentioned, I think we've got the best opportunity, right?

Speaker Change: We're very confident that when we look at symptoms in our phase three it is going to show meaningful benefit compared to Selinexor alone as as Richard mentioned I think we've got the best opportunity right. We have an ongoing phase three it's currently enrolling we do know that the environment is evolving both for.

Reshma Rangwala: We have an ongoing Phase 3. It's currently enrolling patients. We do know that the environment is evolving, both from a physician perspective, but also from an FDA perspective, and we're going to capitalize on that.

Speaker Change: A physician perspective, but also from an F D. A perspective, and we're going to capitalize on that so you know if there's an opportunity to evolve the end point, we have an opportunity to then of course incorporate those into our study you know prior to that the database lock.

Reshma Rangwala: So, if there's an opportunity to evolve the endpoints, we have an opportunity to then, of course, incorporate those into our study prior to the database launch. Okay, that's helpful. And maybe one other question.

Okay. That's helpful and maybe one other question you plan to report the preliminary results from the mono therapy pays to Jack naive myelofibrosis with moderate thrombocytopenia in the second half of this year can you talk more about what the strategy is for that study is this for.

Reshma Rangwala: You plan to report the preliminary results from the monotherapy phase to inject naive myelofibrosis with moderate thrombocytopenia in the second half of this year. Can you talk more about what the strategy is for that study? Is this for a potential standalone monotherapy approval path or more for supplementing the combination filing? Yeah, great question. So one of the unique aspects of Selenexor is that when we look at preclinical data, obviously clinical data from a relapsed refractory myelofibrosis study, which is the essential study, and then, of course, the subgroup data from our phase one Selenexor plus Ruxolitinib phase, it all points to very intriguing monotherapy activity. Again, this is unique. When you look at other mechanisms of action, whether it's a BET inhibitor or a BCL-2 inhibitor, those agents, by and large, do not have that critical monotherapy activity.

Potential standalone monitor P approval path or more for supplementing the combination filing and Michael.

Speaker Change: Yeah, Great question. So one of the unique aspects of Selinexor is that when we look at preclinical data obviously clinical data from a relapse refractory Myelofibrosis study, which is the essentials study and then of course, the subgroup data from our phase one Selinexor pus Ruxolitinib <unk>.

Michael: All points to very intriguing monotherapy activity again. This is unique when you look at other mechanisms mechanisms of action, whether it's a button inhibitor D. C. L. Two inhibitor those agents by and large do not have that critical monotherapy activity. It's key that <unk> that physicians ultimately have that flexibility.

Reshma Rangwala: It's key that physicians ultimately have that flexibility and that dosing. We want to use this phase two study to further investigate this monotherapy activity in this high-at-net patient population. We'll have an opportunity to read out some data later this year and really be able to identify whether that activity is meaningful, again, in that high-at-net-need patient population. We're really looking at this as a proof of concept study. Potentially, we can expand it, potentially get some NCCN, but right now, it's really to double down and better test this hypothesis that we have with Selenexor again in this JAK-naive population.

Michael: That dosing uhm.

Michael: We want to use this phase two study to further investigate this monotherapy activity in this high at net patient population will have an opportunity to read out some data up later this year and and really be able to identify whether that activity is meaningful again isn't that high net need patient popular.

Michael: <unk>, we're really looking at this as a proof of concept study you know potentially we can expand it potentially get some M. C. C N, but right now it's really the double down and better test. This hypothesis that we have with selling next door again and distract naive population.

Reshma Rangwala: Got it. Okay. Thanks for taking my question. Thanks, Maury. And your next question comes from the line of Jonathan Chang from Leering Partners. Your line is open.

Speaker Change: Got it okay. Thanks for taking my questions.

Speaker Change: Thanks for Ya.

Speaker Change: And your next question comes from the line Jonathan Chang from leaving partners. Your line is open.

Richard A. Paulson: Hi guys, thanks for taking my questions. First question, can you speak to the enrollment experience for the phase three SPD triplet study in multiple myeloma? And then, second question, can you talk about how you're thinking about your cash position and runway and the converts due to mature in October of 2020? Yeah, thanks, Jonathan. For the first part of that, I'll turn to Reshma, and then I'll let Mike talk about the second part of that.

Jonathan Chang: Hi, guys. Thanks for taking my questions first.

Jonathan Chang: First question can you speak to the enrollment experience of the Faith Street S. P. D. Triplets study in multiple myeloma and then second question can you talk about how you're thinking about your cash position and runway and the converts due to mature in October of 2025. Thank you.

Jonathan Chang: Yeah. Thanks, Jonathan for the first part of that I'll I'll turn to duration Madden N O at Mike touch on the second part of that.

Reshma Rangwala: Yeah, thanks, Jonathan, for the question. So the enrollment is going well with that XPD trial. It's an all oral, as Sohanya mentioned, you know, SPD really represents the only all oral therapy.

Nolan: Yeah. Thanks, Jonathan further questions. So the enrollment is going well with that X P. D trial. It's an all oral is behind you mentioned you know S. P. D really represents the only all oral therapy. Obviously it has some unique data pre and post T cell therapies, which in this evolving environment.

Reshma Rangwala: Obviously, it has some unique data pre and post T cell therapy, which in this evolving environment is going to be a key attribute for this combination. There's a lot of interest in this study, both in the US as well as in the EU. So we're driving towards enrollment and look forward to announcing completion of enrollment later this year. Thanks. And on the second question, yes, we finished 2023 with $192 million in cash, and we burned approximately $88 million in 2023, which gives us a cash runway with, you know, our plans for Expovio Net Revenues here in the US, as well as partnership revenues offset by, you know, spend over the next couple years into late 2025. And as far as the convert goes, the convert is due in October 2025. So it certainly gives us some time. It's very closely held, with the top five holders owning greater than 85% of the bond.

Nolan: It's gonna be a key attribute for this combination there's a lot of interest in this study both in the U S as well as the E. U. So we're driving towards enrollment and look forward to yeah announcing completion of the enrollment later this year.

Speaker Change: Thanks and on the second question, Yes, we finished 2023 with $192 million in cash weed burner, approximately 88 million in 2023, which gives us a cash run away with.

Speaker Change: You know what we're planning for Expo your net revenues here in the U S as well as partnership revenues offset by <unk>.

Speaker Change: Spend over the next couple of years until late 2025.

Speaker Change: And as far as the convert goes to the convert is due in October 2025. So it certainly gives us some time, that's very closely held with the top five holders owning a greater than 85 per cent of the bonds. So, we'll certainly be opportunistic and evaluate our options around the around the corner.

Mike: So we'll certainly be opportunistic, you know, in evaluating our options around that around the convert. Got it. Thanks for taking my question. Thanks, Jonathan. And your next question comes from the line of Colleen Kusy from Baird. Your line is open. Great. Good morning.

Speaker Change: Got it thanks for taking my questions.

Speaker Change: Mmm.

Speaker Change: Thanks, Jonathan.

Speaker Change: And your next question comes from the line of <unk>. Your line is open.

Unknown Executive: Thanks for taking our questions. Any comments you can offer on 1Q so far? I think you had mentioned last year that the third party reimbursement foundations wouldn't be as impactful this year with IRA coming online. So can you just give us anything notable with the IRA rollout so far this year, any seasonality you're seeing yet?

Speaker Change: Great. Good morning, Thanks for taking our questions any come in you can offer on one too. So far I think you you had mentioned last year that the third party reimbursement foundations wouldn't be as impactful this year with I R. A coming on online. So can you just uhm anything notable with the I R. A roll out so far this year at any she's now you're seeing yeah, one too.

Unknown Executive: Yeah, thanks, Colleen. I mean, I'll just talk about that at a high level, you know; we just don't provide comments in this kind of interquarter. So we'll update you on Q1. But, you know, as we're progressing through Q1 here, we feel very good about being able to deliver our full year guidance. Unknown Speaker Great. And then, with some exciting label expansion opportunities ahead, can you just make some comments, remind us of your IP position for Selenex, or when does the composition of matter expire? And how long do you think you could be protected beyond that?

Speaker Change: Yeah, Thanks for calling out I mean, I was talking about that at a at a high level you know we were.

Speaker Change: We just don't provide comments kind of intraquarter, so well, we'll update on on Q1, but.

Speaker Change: Progressing in Q1 here, we feel very good about being able to deliver a full year guidance.

Speaker Change: Great and then <unk> wisdom exciting label experienced opportunity. The head can you just make some comments remind us on your I P physician for Selinexor when does the composition matter expire and how long do you think you could be protected beyond that.

Richard A. Paulson: Yeah, thanks, Colleen. You know, as you know, I think we've had some really positive evolution with regard to our IP position. And obviously, we work, we work very hard to make sure we protect our valuable inventions here in the US and globally.

Speaker Change: Yeah. Thanks for calling you know as you know I think we've had some really positive evolution with regards to our our I T position and obviously, we work we work very hard to make sure we protect our valuable inventions here in the U S and globally.

Richard A. Paulson: Last year, you know, in Q3, we were able to achieve kind of almost one year and 342 days of extension to our Composition of Matter patent. So that takes us to July of 2033. And then in Q4 of last year, actually, we were able to, you know, really work with the Patent Office and enabled to enhance our patents with regard to the polymorphic form of Selenexor, and the newly issued patents expire in August of 2035. And we really believe that these polymorphic forms used our API differentiated from other forms and really offers clear and novel benefits. So you know, for us, there is a long runway in front of us with regard to patent protection. Great, that's helpful.

Speaker Change: Last year, you know in Q3, we were able to achieve kind of <unk>.

Speaker Change: Most one year 342 days of extension to our composition of matter pattern. So that takes us to July of 2033.

Speaker Change: And then in Q4 of last year actually we were able to really work with with fat in the office and and able to enhance our patents with regard to the pollen mulford form of Selinexor and the newly issued patents expire in August of 2035, and we really believe that these polymorphic form use.

Speaker Change: <unk> R. I a P. I, it's differentiated from other forums and really offers clear and all the benefits. So you know for US a long runway in front of us with regards to that and protection.

Speaker Change: Great. That's helpful. Thanks for taking my questions.

Colleen Margaret Kusy: Thanks for taking our, Thanks Colleen. And your next question comes from the line of Brian Abrahams from RBC Capital Markets. Markets, your line is open.

Speaker Change: Excellent.

Speaker Change: And your next question comes from the lineup, Brian Apprehends spam RBC capital markets.

Mike: Hi, this is Joanne for Brian. Thanks for taking our question. Question on the new monotherapy study in MS. I believe you're allowing add-on therapies in the study. Can you talk about how many patients are expected to go on add-on therapies over the course of the study? And also any synergistic benefits you may expect to see with Pecoritinib and Momoletinib? Thank you. Yeah, thanks, Joe.

Brian: Your line is open.

Brian: Hi, This is Joanne for Brian. Thanks for taking my question question on the New monotherapy study in M. S. I believe you are allowing had on therapies in the study.

Joanne: Can you talk about how many patients are expected to <unk> head on therapies over the course of the study and also any synergistic benefits. You may you may expect to see them with that great Nathan I'm on my leg ma'am. Thank you.

Brian: Yeah. Thanks, Thanks, Joe I think when when.

Speaker Change: I'm sorry, [laughter] go go ahead ratio, but [laughter] I I <unk> I apologize. This is a great question Joe Uhm. So the monotherapy study as you mentioned correctly does allow the option to add on different therapies as early as week 12, now with that said you know if the patient is.

Unknown Executive: Go ahead, Reshma. I jumped the gun. I apologize. It's a great question, Joe. So the monotherapy study, as you mentioned correctly, does allow the option to add different treatments as early as week 12. Now, with that said, you know, if the patient is deriving benefit, both from an SVR and TSS perspective, we really want them to continue on Selenix or monotherapy. And as I mentioned earlier, given all of the preclinical and clinical data, we really do feel confident that Selenix or monotherapy is going to drive that benefit across those two endpoints, which really suggests that a very small proportion of patients are likely going to need an add-on therapy in the form of momoletinib, picritinib, or rexalitinib.

Speaker Change: Arriving benefit both from an F. B R. A N T. S. S perspective, we really want them to continue on Selinexor monotherapy N. As I mentioned earlier, given all of the preclinical and clinical data, we really do feel confident that selinexor monotherapy is going to drive that benefit across those two end points. We truly suggests that a very small proportion.

And if that is likely going to need an AD on therapy in the form of <unk> or Ruxolitinib. So you know, we'll we'll wait to see is the study continues to roll out and as we see additional patients receive patients you know being enrolled on the study, but but again I I think it is going to be <unk>.

Reshma Rangwala: So, you know, we'll wait to see as the study continues to roll out. And as we see additional patients, we see patients, you know, being enrolled in the study. But again, I think it is going to be a small proportion of patients. Thanks so much. Thanks, Joe. And your next question comes from the line of Steve Bursey from H.C. Wainwright. Your line is open.

Speaker Change: <unk> proportion of patients.

Speaker Change: Thank you so much.

Speaker Change: Thanks, Joe.

Speaker Change: And your next question comes from the line that says Steve Bursey from H C. Wainwright. Your line is open.

Reshma Rangwala: Hey, this is Steve on for Ed. So you were saying there was a shift, more of a shift than the earlier lines of therapy and the increased duration of patient on drug therapy. Can you put any numbers to that?

Steve Bursey: Hey, this is Steven for.

Steve Bursey: You were saying there was a shift more of a shift into earlier lines of therapy and the increased duration.

Steven: A patient on drug can you put any numbers to that and.

Unknown Executive: And, Is there a difference between the second line, the fourth line, and penile refractory patients? Yeah, thanks, Steve. I'm just at a high level to talk about that. We know that looking at the numbers in detail is very difficult, and it's more directional. And I'll turn to Sohanya to talk about that impact as we're looking at the ongoing shift into the earlier lines, which again is right in line with our strategy and where we're going to continue to focus. Sohanya.

Steve Bursey: Is there a difference between a second line the fourth one and pen refractory patients.

Speaker Change: Yeah. Thanks to even I was just at a high level you talk to that we know that you know looking at the numbers in detail is very difficult and smart directional I'll turn to so I need to talk about the impact as we're looking at the ongoing shift into the airlines. Once again. It is right now my Arthur strategy in and we're going to continue to focus Sonya.

Sohanya Cheng: Yeah, so we continue to see an upward trend in our duration of therapy, and that is really primarily driven by the earlier line patients who do tend to stay on therapy much longer than the later line patients. We are also seeing the duration increase because our physicians are getting more comfortable managing these patients with the right supportive care at the lower dose and so on. So, again, we won't disclose the specifics of the duration, but we see an upward trend and we expect to continue to see a positive shift in our duration as we move forward. Okay, thanks for taking our question. Thanks, Steve. Thank you. Our Q&A session has now ended. I would like to turn it back to Richard Paulson, President and Chief Executive Officer of Karyopharm, for closing comments.

Speaker Change: Yeah. So we continue to see an upward trend in duration of therapy and that is really primarily driven by the earlier line patients who do tend to stay on therapy much longer than the Layla later lying patients.

Speaker Change: We are also seeing the duration increase because our physicians are getting more comfortable in managing these patients with the right supportive care at the lower dose and so on so again, what won't disclose the specifics of the duration, but we see an upward trend N and we expect to continue to see a policy shift in our.

Speaker Change: Our duration as we move forward.

Speaker Change: Okay. Thanks for taking our questions.

Speaker Change: Thanks to you.

Speaker Change: Thank you I can eat session has now ended I would like to turn it back to reach Mike Paulson, President and Chief Executive Officer, <unk>, the closing comments.

Richard A. Paulson: Thank you Odie and once again, thank you everyone for joining us today I think as I mentioned before we're very excited about our innovation and growth strategy.

Richard A. Paulson: Phase three clinical trials are are moving forward rapidly and we believe the largest opportunities for selinexor yet to come as we focus on delivering this next phase of growth and as I mentioned, everybody inside a carryover arm is focused on his driving each day for patients I unmet needs and working to generate value for our patients and shareholders. So once again, thank you for joining.

Sohanya Cheng: Thank you, Udi. And once again, thank you, everyone, for joining us today. I think, as I mentioned before, we're very excited about our innovation and growth strategy. Our phase three clinical trials are moving forward rapidly. And we believe, you know, the largest opportunities for selling XOR are yet to come, as we focus on delivering this next phase of growth. And as we mentioned, everybody inside Karyopharm is focused on flourishing each day for patients with high unmet needs and working to generate value for our patients and shareholders. So once again, thank you for joining us today. Thank you, and ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. www.thevenusproject.com

Yesterday.

Speaker Change: Thank you and ladies and gentlemen, this <unk> conference call. Thank you for participating you may not disconnect.

Speaker Change: [noise].