Q2 2024 Karyopharm Therapeutics Inc Earnings Call

Carolyn: Good morning, my name is Carolyn and I will be your conference operator today. At this time, I would like to welcome everyone to Karyopharm Therapeutics' second quarter 2024 financial results conference call.

Operator: At this time, I would like to welcome everyone to Karyopharm Therapeutics' 2nd 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 premises.

Operator: There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request.

Elhan Webb: 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.

Unknown Executive: I would now like to turn the call over to Elhan Webb's Senior Vice President, Investor Relations.

Elhan Webb: Thank you, Carolyn, and thank you all for joining us on today's conference call to discuss Care of Farm second quarter, Q2, 2024 financial results and recent company progress. We issued the press release this morning, detailing our financial results for Q2 2024. This release, along with a slide presentation that will reference during our call today, are available on our website.

Unknown Executive: Thank you, Carolyn. And thank you all for joining us on today's conference call to discuss Karyopharm's second quarter Q2 2024 financial results and recent company progress. Before we begin our formal comments, I remind you that various remarks we'll make today constitute forward-looking statements, FLS.

Elhan Webb: Thank you, Carolyn. And thank you all for joining us on today's conference call to discuss Karyopharm's second quarter Q2 2024 financial results and recent company progress.

Speaker Change: We issued a press release this morning detailing our financial results for Q2 2024.

Speaker Change: This release, along with a slide presentation that we'll reference during our call today, are available on our website.

Elhan Webb: For today's call, I've seen on slide 2, I'm joined by Richard Rajma, Sohanya, and Mike. We'll provide an update on our results for Q2, 2024, and recent clinical developments.

Speaker Change: For today's call, as seen on slide 2, I'm joined by Richard, Reshma, Sohanya, and Mike who will provide an update on our results for Q2 2024 and recent clinical developments.

Elhan Webb: Before we begin our formal comments, I'd remind you that various remarks will make today constitute forward-looking statements, SLS, for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995, as outlined on slide 3. As she results made, if her material is from those indicated by this SLS, as a result of various important factors, including those discussed in the risk factor section of our most recent report, which is on file with the SEC, and in other filings that we may make with the SEC in the future, any SLS 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, FLS,

Speaker Change: for purposes of the safe harbor provisions under the Privacy, Security, and Litigation Reform Act of 1995, as outlined on slide 3.

Speaker Change: Actual results may differ materially from those indicated by this FLS.

Speaker Change: As a result of various important factors, including those discussed in the risk factors section of our most recent Form 10-Q , which is on file with the SEC, and in other filings that we may make with the SEC in the future, any FLS represent our views as of today only.

Elhan Webb: While we may elect to update these SLS at some point in the future, we specifically display an annual obligation to do so, even if our views change. Therefore, you should not rely on these SLS as representing our views as of any later date.

Speaker Change: While we may elect to update these FLS at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these FLS as representing our views as of any later date.

Elhan Webb: I will now turn the call over to Richard, so you start to slide forth.

Speaker Change: I will now turn the call over to Richard. Please turn to slide 4.

Richard Rajma: Good morning. Thank you all, hand, and thank you all for joining us today for Cario Farms Q2, 2024 earnings call.

Richard: Good morning. Thank you, Elhan, and thank you all for joining us today for Karyopharm's Q2 2024 earnings call.

Richard Rajma: Turning to slide 5, I would like to first focus on our innovation and growth strategy, as we work to deliver our next stage of growth by advancing our late stage pipeline, while continuing to strengthen our foundation in multiple Maywama. Starting with Maywama fibrosis, we are more excited than ever regarding seven exorce potential opportunity in this indication. Physician interest in rolling patients into our phase 3 study is strong, and the competitive environment continues to evolve favorably for us. Building on our strong clinical data, the new pre-clinical data that we presented at EHA further reinforces the role that SLS might play in Maywama fibrosis.

Richard: Turning to slide five, I would like to first focus on our innovation and growth strategy as we work to deliver our next stage of growth by advancing our late-stage pipeline while continuing to strengthen our foundation in multiple myeloma.

Richard: Starting with myelofibrosis, we are more excited than ever regarding Selenexor's potential opportunity in this indication.

Richard: Physician interest in enrolling patients into our Phase 3 study is strong, and the competitive environment continues to evolve favorably for us.

Richard: Building on our strong clinical data, the new preclinical data that we presented at EHA further reinforces the role that Salinexort might play in myofibrosis.

Reshma Rangwala: In Endometrial Cancer, we presented updated data at ASCO demonstrating nearly 40 months of progression-free survival when Selenexor is used as a maintenance therapy in patients whose tumors are TP53 wild-type PMMR, giving us confidence to raise the low end of our revenue guidance for 2024.

Richard Rajma: In endometrial cancer, we presented updated data at ASCO demonstrating nearly 40 months of progression-free survival. When seven exor is used as a maintenance therapy in patients whose tumors are TPP-53 wild type PMMR. This population represents approximately half of all patients who are diagnosed with endometrial cancer. It is noteworthy that the progression-free survival that cell next door is demonstrating in the maintenance setting in this subgroup exceeds the overall survival that is achieved by the checkpoint inhibitors in patients whose tumors are PMMR. As we continue to enroll patients in our EC-042 phase 3 trial and endometrial cancer, we are also confronting the complexities of a molecularly targeted maintenance trial and are taking proactive action, both of what Hiroshima will expand on.

Richard: In Endometrial Cancer, we presented updated data at ASCO demonstrating nearly 40 months of progression-free survival when Selenexor is used as a maintenance therapy in patients whose tumors are TP53 wild-type TMMR.

Richard: This population represents approximately half of all patients who are diagnosed with endometrial cancer.

Richard: It is noteworthy that the progression-free survival that CellNexor is demonstrating in the maintenance setting in this subgroup exceeds the overall survival that is achieved by the checkpoint inhibitors in patients whose tumors are PMMR.

Richard: As we continue to enroll patients in our EC042 Phase III trial on endometrial cancer, we are also confronting the complexities of a molecularly targeted maintenance trial and are taking proactive actions, both of which Reshma will expand on.

Richard Rajma: As a result, we now expect to deliver top-line data in early 2026.

Reshma: As a result, we now expect to deliver top-line data in early 2026.

Richard Rajma: In multiple myeloma, we are pleased to report our second consecutive quarter of growth in expolvio revenue, giving its confidence to raise the low end of our revenue guidance for 2024. The importance of Expolvio's differentiated mechanism of action, its all oral administration, and potentially T-cell-sparing impact, is increasingly resonating with community and academic physicians, which Sohanya will expand on. As we work to build on our commercial foundation in multiple myeloma, we expect to leverage our positively evolving SPD data at the 40 milligram dose to update the design of the phase 3 AMN 29 trial, which will include targeting fewer participants for enrollment and lowering the projected cost of this trial.

Reshma: In multiple myeloma, we are pleased to report our second consecutive quarter of growth in expovial revenue.

Reshma: Giving us confidence to raise the low end of our revenue guidance for 2024.

Sohanya: The importance of Expovio's differentiated mechanism of action, its all-oral administration, and potentially T-cell-sparing impact is increasingly resonating with community and academic physicians, which Sohanya will expand on.

Sohanya: As we work to build on our commercial foundation of multiple myeloma, we expect to leverage our positively evolving SPD data at the 40 mg dose to update the design of the Phase III EMN29 trial.

Sohanya: which will include targeting fewer participants for enrollment and lowering the projected cost of this trial.

Richard Rajma: Finally, in light of our strengthening commercial performance, disciplined cost management, and focused approach to clinical development, we believe we're in a strong financial position to deliver on our prioritized late-stage pipeline. Mike will expand on our lowered 2024 R&D and SG&A expense guidance. We continue to be very optimistic about our next stage of growth, and our well position to capitalize on the opportunities for Selenex or with our diversely built late stage pipeline across three different cancer indications. We continue to believe the annual peak revenue opportunity for Selenex or could be two billion dollars in the U.S.

Sohanya: Finally, in light of our strengthening commercial performance, disciplined cost management, and focused approach to clinical development, we believe we're in a strong financial position to deliver on our prioritized late-stage pipeline.

Sohanya: Mike will expand on our lowered 2024 R&D and SG&A expense guidance.

Mike: We continue to be very optimistic about our next stage of growth and are well positioned to capitalize on the opportunities for Cellinexor with our diversely built late-stage pipeline across three different cancer indications.

Mike: We continue to believe the annual peak revenue opportunity for Selenexor could be $2 billion in the U.S. alone.

Richard Rajma: alone.

Reshma Rangwala: I would now like to turn the call over to Raishima to expand on our recent data announcements and discuss our progress with each of the programs in our pipeline.

Reshma: I would now like to turn the call over to Reshma to expand on our recent data announcements and discuss our progress with each of the programs in our pipeline. Reshma.

Reshma Rangwala: Raishima. Thank you, Richard.

Reshma Rangwala: Turning to slide 7, I'd like to highlight our promising late-stage pipeline led by Selenex or three ongoing phase 3 studies, each of which has the potential to enable a new standard of care, continuing to build upon the growing body of data and utilizing the once-weekly lower doses of either 40 or 60 milligrams. We continue to be very encouraged by the data generated to date, supporting our three pivotal phase 3 trials, including the improving long-term follow-up data and endometrial cancer from the exploratory subgroup analysis in the CNDO trial that was presented at ASCO, which I'll expand on shortly.

Reshma: Thank you, Richard.

Reshma: Turning to slide 7, I'd like to highlight our promising late-stage pipeline led by Selenexor's three ongoing Phase III studies.

Reshma: Each of which has the potential to enable a new standard of care, continuing to build upon the growing body of data and utilizing the once weekly lower doses of either 40 or 60 milligrams.

Reshma: We continue to be very encouraged by the data generated to date supporting our three pivotal Phase 3 trials, including the improving long-term follow-up data in endometrial cancer from the exploratory subgroup analysis in the CIENDO trial that was presented at ASCO, which I'll expand on shortly.

Reshma Rangwala: Starting with MiloFibrosis on slide 9, we are incredibly excited by both our evolving data and physician interest in our work in this area. In June, we presented new preclinical data at the European Hematology Association hybrid congress. These data demonstrated the strong mechanistic rationale of XP01 inhibition in MiloFibrosis and the ability to target both the Jack and non-Jack pathways. In light of our data that show that XPO1 inhibits both Jack and non-Jack pathways, we believe that Selenexor can be leveraged both in combination and as a monotherapy.

Reshma: Starting with myelofibrosis on slide 9, we are incredibly excited by both our evolving data and physician interest in our work in this area.

Reshma: In June , we presented new preclinical data at the European Hematology Association Hybrid Congress.

Reshma: These data demonstrated the strong mechanistic rationale of XPO1 inhibition in myelofibrosis and its ability to target both the JAK and non-JAK pathways.

Reshma: In light of our data that show that XPO1 inhibits both JAK and non-JAK pathways, we believe that Selenexor can be leveraged both in combination and as a monotherapy.

Reshma Rangwala: We presented data from our phase one trial in mylofibrosis last year, as seen on slide 10. Selenexor 60 milligrams was evaluated in combination with rectilitinib in Jack and Hibiter naïve patients. Of the 14 patients who received the 60 milligram dose of Selenexor, 79% and 58% achieved a SVR 35 and TSS 50 at week 24, respectively. Absolute TSS demonstrated very meaningful improvements, with an average reduction of 18.5 points at week 24 in the efficacy of valuable population. Diving deeper into the important aspect of durability on slide 11, as of the data cut off, there was 100% probability of continuing responses in both the SVR 35 and TSS 50 over a median duration of follow-up of 32 weeks and 51 weeks respectively when Selenexor 60 milligrams was used in combination with rectilitinib, indicating that the responses are maintained well beyond 24 weeks.

Reshma: We presented data from our Phase 1 trial in myelofibrosis last year, as seen on slide 10.

Reshma: Felinexor 60 mg was evaluated in combination with rexalitinib and JAK inhibitor naïve patients.

Reshma: Of the 14 patients who received the 60 mg dose of Selenexor, 79% and 58% achieved a SVR35 and TSS50 at week 24, respectively.

Reshma: Absolute TSS demonstrated very meaningful improvements with an average reduction of 18.5 points at week 24 in the efficacy of valuable population.

Reshma: Diving deeper into the important aspect of durability on slide 11.

Reshma: As of the data cutoff, there was 100% probability of continuing responses in both the SCR35 and TSS50 over a median duration of follow-up of 32 weeks and 51 weeks, respectively.

Reshma: when Selenexor 60 mg was used in combination with ruxolitinib, indicating that the responses are maintained well beyond 24 weeks.

Reshma Rangwala: These findings support the potential of the combination of Selenexor plus rectilitinib to offer greater symptom improvement than rectilitinib alone, as our ongoing phase three study may demonstrate.

Reshma: These findings support the potential of the combination of selinexor plus ruxolitinib to offer greater symptom improvement than ruxolitinib alone, as our ongoing Phase 3 study may demonstrate.

Reshma Rangwala: Moving to slide 12, we outlined the trial design for our Phase Three-Century trial, evaluating the combination of Selenexor 60 milligrams with Rectilitinib compared to Rectilitinib alone in 306 Jack Nyev Milo-Fibrosis patients. We are encouraged by the strong enrollment into our phase three clinical trial given by the positive feedback that we are hearing from clinical trial investigators regarding Selenexor's unique mechanism and clinical profile. Our momentum is also fueled by minimal competitive clinical activity and posse as effective therapies. Our guidance for reporting top-line results remains firmly on track for the second half of 2025.

Reshma: Moving to slide 12, we outline the trial design for our phase 3 sentry trial, evaluating the combination of Selenexor 60 mg with Ruxolitinib compared to Ruxolitinib alone in 306 jack-naive myelofibrosis patients.

Reshma: We are encouraged by the strong enrollment into our Phase 3 clinical trial given by the positive feedback that we are hearing from clinical trial investigators regarding Selenexor's unique mechanism and clinical profile.

Reshma: Our momentum is also fueled by minimal competitive clinical activity and POSSE as effective therapies. Our guidance for reporting top-line results remains firmly on track for the second half of 2025.

Reshma Rangwala: Turning our attention to endometrial cancer on slide 14, one of Selenexor's primary mechanisms is to suppress the export of p53 from the nucleus to the cytoplasm. The accumulation of P53 in the nucleus leads to impaired DNA repair, cell cycle arrest, and ultimately increased apoptosis. Clinically, this mechanism is what drives anti-tumor activity in tumors dependent upon p53, including endometrial cancer. Advanced and recurrent endometrial cancers, the most common form of gynecologic cancer in the United States, with approximately 16,000 patients diagnosed each year. We believe Selenexor could play an important role for greater than half of these patients as the first novel oral maintenance therapy for patients with P53 wild-type tumors.

Speaker Change: Turning our attention to endometrial cancer on slide 14, one of Felinexport's primary mechanisms is to suppress the export of P53 from the nucleus to the cytoplasm.

Speaker Change: The accumulation of p53 in the nucleus leads to impaired DNA repair, cell cycle arrest, and ultimately increased apoptosis.

Speaker Change: Advanced and Recurrent Endometrial Cancer is the most common form of gynecologic cancer in the United States, with approximately 16,000 patients diagnosed each year.

Speaker Change: We believe Selenexor could play an important role for greater than half of these patients as the first novel oral maintenance therapy for patients with TP53 wild-type tumors.

Reshma Rangwala: Selenexor's slide 15, P53 wild type status has an emerging role in the evolving landscape of advanced and recurrent endometrial cancer. Checkpoint inhibitors were recently improved by the FDA in combination with chemotherapy, followed by checkpoint inhibitor maintenance for advanced recurrent endometrial cancer patients, regardless of MMR status. However, the efficacy observed in patients whose tumors are PMMR is markedly less than in the DMMR, consistent with the mechanistic rationale for checkpoint inhibitor effectiveness in DMMR solid tumors. These checkpoint inhibitors have been included in combination with chemotherapy followed by checkpoint inhibitor maintenance in the NCCN guidelines for all patients regardless of MMR status since March of 2023. Patients whose tumors are both PMMR and P53 wild type represent roughly 50% of all exams are recurrent endometrial cancer patients.

Speaker Change: As seen on slide 15, TP53 wild-type status has an emerging role in the evolving landscape of advanced and recurrent endometrial cancer.

Speaker Change: Checkpoint inhibitors were recently improved by the FDA in combination with chemotherapy, followed by checkpoint inhibitor maintenance for advanced recurrent endometrial cancer patients, regardless of MMR status.

Speaker Change: However, the efficacy observed in patients whose tumors are pMMR is markedly less than in the dMMR, consistent with the mechanistic rationale for checkpoint inhibitor effectiveness in dMMR solid tumors.

Speaker Change: These checkpoint inhibitors have been included in combination with chemotherapy, followed by checkpoint inhibitor maintenance in the NCCN guidelines for all patients, regardless of MMR status, since March of 2023.

Speaker Change: Patients whose tumors are both PMMR and p53 wild-type represent roughly 50% of all advanced or recurrent endometrial cancer patients.

Reshma Rangwala: Turning to slide 16 at ASCO, we presented very encouraging long-term follow-up data from the exploratory analysis of C&O, which evaluated cell and exorbitant in therapy patients with P53 wild type PMMR tumors. Experienced a median PFS at 39.5 months with cell and exor compared to 4.9 months with placebo, resulting in a hazard ratio of 0.36. Acknowledging the limitations in cross trial comparisons, the median PFS improvement achieved with cell and exor in the subgroup exceeds the median overall survival achieved by checkpoint inhibitors and PMMR patients, underscoring the meaningful efficacy achieved with cell and exor in these patients.

Speaker Change: Turning to slide 16, at ASCO we presented very encouraging long-term follow-up data from the exploratory analysis of Siendo, which evaluated Selenexor as a maintenance therapy.

Speaker Change: Patients with P53 wild-type PMMR tumors experienced a median PFS of 39.5 months with Selenexor compared to 4.9 months with placebo, resulting in a hazard ratio of 0.36.

Speaker Change: Acknowledging the limitations in cross-trial comparisons, the median PFS improvement achieved with Selenexor in this subgroup exceeds the median overall survival achieved by checkpoint inhibitors in PMMR patients.

Speaker Change: Underscoring the meaningful efficacy achieved with Selenexor in these patients.

Reshma Rangwala: In all patients with P53 wild type tumors, cell and exor demonstrated promising benefit, with a median PFS of 28.4 months compared to 5.2 months for placebo, resulting in a hazard ratio of 0.44. These robust exploratory subgroup data from C&O continued to demonstrate the potential of cell and exor to provide substantial benefit in a unique and sizable population. In a survey of US positions who were provided long-term follow-up data achieved with cell and exor in patients with tumors are P53 wild type from the C&O study, as well as efficacy with the checkpoint inhibitors, 75% indicated future intent to prescribe cell and exor as a maintenance therapy for P53 wild type PMMR endometrial cancer patients.

Speaker Change: In all patients with P53 wild-type tumors, Selenexor demonstrated promising benefit with a median PFS of 28.4 months, compared to 5.2 months for placebo, resulting in a hazard ratio of 0.44.

Speaker Change: These robust exploratory subgroup data from CIANDO continue to demonstrate the potential of Selenexor to provide substantial benefit in a unique and sizable population.

Speaker Change: In a survey of U.S. physicians who were provided long-term follow-up data achieved with Selenexor in patients whose tumors are P53 wild-type from the Ciendis study, as well as efficacy with the checkpoint inhibitors,

Speaker Change: 75% indicated future intent to prescribe Felinexor as a maintenance therapy for P53 wild-type PMMR endometrial cancer patients.

Reshma Rangwala: Overall, we believe that cell and exor were to be approved in this indication, a majority of patients could benefit from this treatment option.

Speaker Change: Overall, we believe if Selenexor were to be approved in this indication, a majority of patients could benefit from this treatment option.

Reshma Rangwala: Let's also review the updated safety data on endometrial cancer from the Sander trial that we presented at ASCO, as shown on slide 17. Adverse events were generally manageable and well tolerated. The most common AES observed with cell and exor, regardless of grade, were nausea of vomiting and diarrhea. It is important to note that dual antiemetics were not required in this trial. Grade 3 plus treatment-emergent adverse events were rare, with the most common events being neutropenia, thrombocytopenia, and nausea.

Speaker Change: Let's also review the updated safety data on endometrial cancer from the CANDOR trial that we presented at ASCO, as shown on slide 17.

Speaker Change: Adverse events were generally manageable and well-tolerated. The most common AEs observed with sulinexor, regardless of grade, were nausea, vomiting, and diarrhea.

Speaker Change: It is important to note that dual anti-emetics were not required in this trial. Grade 3 plus treatment emergent adverse events were rare, with the most common events being neutropenia, thrombocytopenia, and nausea.

Reshma Rangwala: Finally, on Slide 18, and as Richard mentioned, we are shifting our expected timeline for the top-line data readout for our pivotal Export EC042 Phase 3 trial to early 26. Based on recent observations, an increasing interval between biopsy evaluation and chemotherapy completion has led to a higher than expected screen failure rate. Availability of new therapies is also impacting our enrollment, albeit to a lesser degree. Based upon these observations, we are enhancing our investments by adding additional sites to increase the total number of patients that will need to be screened for this trial. Overall, I continue to be extremely enthusiastic about the potential fuselanexor to provide clinically meaningful outcomes in the maintenance setting for patients with P53 wild type endometrial cancer, especially those with PMMR tumors, where our exploratory subgroup data has demonstrated a median PSS of nearly 40 months, which again exceeds the median overall survival observed with checkpoint inhibitors in patients with PMMR tumors.

Speaker Change: Finally, on slide 18, and as Richard mentioned, we are shifting our expected timeline for the top-line data readout for our Pivotal Export EC042 Phase 3 trial to early 26.

Richard: Based on recent observations, an increasing interval between biopsy evaluation and chemotherapy completion has led to a higher-than-expected screen failure rate.

Richard: Availability of new therapies is also impacting our enrollment, albeit to a lesser degree.

Richard: Based upon these observations, we are enhancing our investments by adding additional sites to increase the total number of patients that will need to be screened for this trial.

Richard: Overall, I continue to be extremely enthusiastic about the potential for Selenexor.

Richard: to provide clinically meaningful outcomes in the maintenance setting for patients with P53 wild-type endometrial cancer, especially those with PMMR tumors.

Richard: where our exploratory subgroup data has demonstrated a median PFS of nearly 40 months, which again, exceeds the median overall survival observed with checkpoint inhibitors in patients with PMMR tumors.

Reshma Rangwala: Lastly, turning to multiple myeloma on Slide 20, we are very encouraged with the results from our STONP and MMO-028 trials that evaluated celinexor 40 milligrams in combination with pomolidamide-indexamethazone. The promising data published in the Frontiers Among College journal in May of this year underscores celinexor's potential to expand its position in the multiple myeloma landscape. Celinexor 40 milligrams demonstrated an updated median PSS of 18.4 months and a very tolerable safety profile. Nausea rates were observed in only 32 percent of patients in the 40 milligram arm, a meaningful improvement relative to the 50 percent that was observed with cellinexor 100 milligram in the Boston trial.

Speaker Change: Lastly, turning to multiple myeloma on slide 20, we are very encouraged with the results from our STOMP and MMO28 trials that evaluated Selenexor 40 milligrams in combination with pomalidomide and dexamethasone.

Speaker Change: The promising data published in the Frontiers of Oncology Journal in May of this year underscored Selenexor's potential to expand its position in the multiple myeloma landscape.

Speaker Change: Selenexor 40 mg demonstrated an updated median PFS of 18.4 months and a very tolerable safety profile.

Speaker Change: Nausea rates were observed in only 32% of patients in the 40 mg arm, a meaningful improvement relative to the 50% that was observed with Selenexor 100 mg in the Boston trial.

Reshma Rangwala: Our ongoing phase 3 trial has the potential to build upon and improve the already favorable data, given that the SOMP and MMO-028 cohorts did not require dual anti-emetics.

Speaker Change: Our ongoing Phase 3 trial has the potential to build upon and improve the already favorable data, given that the SOMP and MMO28 cohorts did not require dual anti-emetics.

Reshma Rangwala: Our Phase 3 EMN-29 SPD trial in multiple myeloma is outlined on Slide 21. This trial is designed to address the unmet need presence in patients with multiple myeloma with an all oral triplet treatment option that can be beneficial to pre and post T-cell engaging therapies. We will be working with a European myeloma network, the sponsor of this study, to leverage the positively evolving PSS data observed with SPD 40 and amend the statistical analysis plan to enable a meaningful interpretation of the efficacy and safety of SPD versus EPD. Importantly, we are also seeing a slowdown in enrollment rates due to an increasingly global competitive trial environment, with an increased number of phase 3 studies targeting the same sites and a similar patient population.

Speaker Change: Our Phase 3 EMN 29 SPD trial in multiple myeloma is outlined on slide 21.

Speaker Change: This trial is designed to address the unmet need present in patients with multiple myeloma with an all-oral triplet treatment option that can be beneficial to pre- and post-T cell engaging therapies.

Speaker Change: We will be working with the European Myeloma Network, the sponsor of this study.

Speaker Change: to leverage the positively evolving PFS data observed with SPD-40 and amend the Statistical Analysis Plan to enable a meaningful interpretation of the efficacy and safety of SPD versus EPD.

Speaker Change: Importantly, we are also seeing a slowdown in enrollment rates due to an increasingly global competitive trial environment, with an increased number of Phase III studies targeting the same sites and a similar patient population.

Reshma Rangwala: In fact, as of today, four large phase 3 trials have already been initiated in 2024. The same number of trials initiated in all of 2023. We now plan to enroll approximately half of the planned sample size, and pending the strength of the data. We will engage with regulatory agencies accordingly. Based upon these revised plans, we continue to anticipate top-line results in the first half of 2025.

Speaker Change: In fact, as of today, four large phase three trials have already been initiated in 2024, the same number of trials initiated in all of 2023.

Speaker Change: We now plan to enroll approximately half of the planned sample size, and pending the strength of the data, we will engage with regulatory agencies accordingly.

Speaker Change: Based upon these revised plans, we continue to anticipate top-line results in the first half of 2025.

Reshma Rangwala: In conclusion, our rapidly advancing pipeline presents near-term late-stage opportunities backed by increasingly compelling data. Solanexor has the potential to benefit multiple cancer patient populations with higher net needs in the near future, enhancing our existing approved indications in multiple myeloma.

Speaker Change: In conclusion, our rapidly advancing pipeline presents near-term, late-stage opportunities backed by increasingly compelling data.

Speaker Change: Selinexor has the potential to benefit multiple cancer patient populations with high unmet needs in the near future, enhancing our existing approved indications in multiple myeloma.

Sohanya Cheng: I will now turn the call to Sohanya for a review of our commercial highlights.

Speaker Change: I will now turn the call to Sohanya for a review of our commercial highlights.

Sohanya Cheng: Thank you, Reshma, and good morning, everyone. On slide 23, I will discuss our commercial highlights for the second quarter of 2024. In the second quarter, exposure net product revenue was 28 million, up 8% compared to our results in the first quarter. And second quarter-over-quarter growth was driven by growth in both new patient starts and refills as exposure is increasingly utilized in a flexible position across the treatment paradigm as a convenient oral regimen with a differentiated mechanism of action.

Unknown Executive: Thank you, Reshma, and good morning, everyone. On slide 23, I will discuss our commercial highlights for the second quarter of 2024. In the second quarter, following the positive recommendation from NICE, expanded reimbursement was achieved in the UK as well as South Korea. Additionally, Expovio continued to expand its global footprint with additional regulatory approvals in China and other international markets. A dedicated commercialization team and partners have the capabilities for rapid launches in potential future indications as well.

Sohanya: Thank you, Reshma, and good morning, everyone. On slide 23, I will discuss our commercial highlights for the second quarter of 2024.

Sohanya: In the second quarter, Expovio net product revenue was $28 million, up 8% compared to our results in the first quarter.

Sohanya: Consecutive quarter-over-quarter growth was driven by growth in both new patient starts and refills as Expovio is increasingly utilized in a flexible position across the treatment paradigm as a convenient oral regimen with a differentiated mechanism of action.

Sohanya Cheng: The results and momentum from the first half of this year and continued strong execution have led us to raise the low end of our net product revenue guidance by 5 million to a new range of 105 to 120 million. New patient mix remains stable in the second to 4 treatment lines, with early aligned use primarily coming from the community setting, which contributed to approximately 60% of exposure net revenues in the second quarter. Demand in the community setting grew more than 10% from the first quarter. Demand in the academic setting remains consistent with the first quarter, with exposure being increasingly used immediately before or after T cell therapies as a way to potentially preserve T cell fitness.

Sohanya: The results and momentum from the first half of this year and continued strong execution have led us to raise the low end of our net product revenue guidance by $5 million to a new range of $105 to $120 million.

Sohanya: New patient mix remained stable in the second to fourth treatment lines, with earlier line use primarily coming from the community setting, which contributed to approximately 60 percent of ExpovioNet revenues in the second quarter.

Sohanya: Demand in the community setting grew more than 10% from the first quarter.

Sohanya: Demand in the academic setting remained consistent with the first quarter with Expovio being increasingly used immediately before or after T-cell therapies as a way to potentially preserve T-cell fitness.

Sohanya Cheng: In academic institutions using expo as a bridging regimen prior to T cell therapy use, we see shorter duration of therapy of expo, but this was offset by the increase in new starts in this setting.

Sohanya: In academic institutions using Expovio as a bridging regimen prior to T-cell therapy use, we see shorter duration of therapy of Expovio, but this was offset by the increase in new starts in this setting.

Sohanya Cheng: Overall, in a highly competitive marketplace, we're very pleased with the results that our commercial organization has delivered in the first half of the year, with consecutive quarter-over-quarter growth.

Speaker Change: Overall, in a highly competitive marketplace, we are very pleased with the results that our commercial organization has delivered in the first half of the year with consecutive quarter-over-quarter growth.

Sohanya Cheng: Now I'd like to turn to slide 24 and shift our focus towards milestones accomplished outside of the US. I'm pleased with our momentum as we expand our global footprint with continued regulatory and reimbursement approvals of Selenex or across the world. In the second quarter following the positive recommendation from NICE, expanded reimbursement was achieved in the UK as well as South Korea. Additionally, EXPOVO continued to expand its global footprint with additional regulatory approvals in China and other international markets. In summary, carrier farms, multiple myeloma franchise continues to impact an increasingly number of patients globally while remaining a profitable business and serving as a critical driver in funding our pipe.

Speaker Change: Now, I'd like to turn to slide 24 and shift our focus towards milestones accomplished outside of the U.S. I am pleased with our momentum as we expand our global footprint with continued regulatory and reimbursement approvals for Selenexor across the world.

Speaker Change: In the second quarter, following the positive recommendation from NICE, expanded reimbursement was achieved in the UK as well as South Korea. Additionally, Expovio continued to expand its global footprint with additional regulatory approvals in China and other international markets.

Speaker Change: In summary, Karyopharm's multiple myeloma franchise continues to impact an increasingly number of patients globally, while remaining a profitable business and serving as a critical driver in funding our pipeline.

Sohanya Cheng: A dedicated commercialization team and partners have the capabilities for rapid launches in potential future indications as well.

Speaker Change: A dedicated commercialization team and partners have the capabilities for rapid launches and potential future indications as well. Now I'd like to turn the call over to Mike to give an update on our financials.

Mike: Now I'd like to turn the call over to Mike to give an update on our financials.

Mike: Good morning everyone, 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 are on slide 26. Total revenue for the second quarter of 2024 was 42.8 million. Reflecting strong momentum compared to 37.6 million for the second quarter of 2023, net US expovia revenue for the second quarter of 2024 was 28 million compared to 28.5 million for the second quarter of 2023. The growth can at discount for expovio in the second quarter of 2024 was 29% as compared to 22% in the second quarter of 2023.

Mike: Good morning, everyone, 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 are on slide 26.

Mike: Total revenue for the second quarter of 2024 was $42.8 million, reflecting strong momentum, compared to $37.6 million for the second quarter of 2023.

Mike: Net U.S. Expovio revenue for the second quarter of 2024 was $28 million, compared to $28.5 million for the second quarter of 2023.

Mike: The GrossConnect discount for Expovio in the second quarter of 2024 was 29%, as compared to 22% in the second quarter of 2023. This was driven by increased 340B utilization, Medicare rebates, and expired product returns.

Mike: This was driven by increased 340 V utilization, Medicare rebates, and expired product returns. We continue to expect 25 to 30% GTN for the full year 2024. Our total expenses for the second quarter of 2024 were up slightly year over year by 6%, driven by our investments in our late stage clinical pipeline with three ongoing phase three trials. R&D expenses for the second quarter of 2024 with 38.4 million compared to 31.5 million for the second quarter of 2023. The increase in R&D expenses is primarily attributable to higher clinical trial costs related to our pivotal phase three programs. SG&A expenses for the second quarter of 2024 were 31 million compared to 34.5 million for the second quarter of 2023.

Mike: We continue to expect 25 to 30% GTM for the full year 2024. We reported net income of $23.8 million for the second quarter of 2024 compared to a net loss. Based on our current operating plans, we are raising the lower end of our guidance for both total revenue and explosive net product revenue by $5 million and lowering and tightening our overall range of expense guidance by $10 to $15 million. Expovio net US product revenue is expected to be in the range of 105 to 120 million as compared to the previous guidance of 100 to 120. In summary, we are focused on the advancement of our three phase three trials and driving commercial performance while continuing I'll now flip to slide 27 and turn the call over to Richard for some final thoughts.

Mike: We continue to expect 25-30% GTN for the full year 2024.

Mike: Our total expenses for the second quarter of 2024 were up slightly year-over-year by 6%, driven by our investments in our late-stage clinical pipeline with three ongoing phase 3 trials.

Mike: R&D expenses for the second quarter of 2024 were $38.4 million, compared to $31.5 million for the second quarter of 2023. The increase in R&D expenses is primarily attributable to higher clinical trial costs related to our pivotal Phase III programs.

Mike: SG&A expenses for the second quarter of 2024 were $31 million compared to $34.5 million.

Mike: The decrease in SGNA expenses was primarily due to ongoing cost reduction initiatives and lower headcount, partially offset by approximately $1 million in debt financing-related expenses. We reported net income of 23.8 million for the second quarter of 2024 compared to a net loss of 32.6 million for the second quarter of 2023. Mostly due to a one-time non-cash net gain of 44.7 million on the extinguishment of debt and 14.3 million in gains that were recognized in connection with the refinancing transactions that we concluded in May, which you can see in detail on the related slide in the appendix.

Mike: for the second quarter of 2023.

Mike: The decrease in SG&A expenses was primarily due to ongoing cost-reducting initiatives and lower headcount, partially offset by approximately $1 million in debt financing related expenses.

Mike: We reported net income of $23.8 million for the second quarter of 2024, compared to a net loss.

Mike: of $32.6 million for the second quarter of 2023.

Mike: Mostly due to a one-time non-cash net gain of $44.7 million on the extinguishment of debt and $14.3 million in gains that were recognized in connection with the refinancing transactions that we concluded in May, which you can see in detail on the related slide in the appendix.

Mike: As a reminder, these transactions extended the vast majority of our majorities into 2028 and 2029, well beyond our expected data readouts from our three phase three trials and potential launches. Cash cash equivalent restricts cash and investments as of June 30th, 2024, total 152.5 million compared to 192.4 million as of December 31, 2023. Based on our current operating plans, we are raising the lower end of our guidance for both total revenue and exposure net product revenue by 5 million and lowering and tightening our overall range of expense guidance by 10 to 15 million. The operating expense reductions for the remainder of 2024 include lower expected expenses for our EMN 29 trial with the plan resizing, as well as continued discipline in our operating costs, including headcount.

Mike: As a reminder, these transactions extended the vast majority of our maturities into 2028 and 2029, well beyond our expected data readouts from our three phase three trials and potential launches.

Mike: Cash, cash equivalents for restricted cash and investments as of June 30, 2024, totaled $152.5 million, compared to $192.4 million as of December 31, 2023.

Mike: Based on our current operating plans, we are raising the lower end of our guidance for both total revenue and explosive net product revenue by $5 million and lowering and tightening our overall range of expense guidance by $10 to $15 million.

Mike: The operating expense reductions for the remainder of 2024 include lower expected expenses for our EMN 29 trial, with the plan resizing, as well as continued discipline in our operating costs, including headcount.

Mike: Specifically, since the beginning of last year, we have reduced our budget headcount by approximately 30%. Our updated guidance ranges for the full year of 2024 hours falls. Total revenue expects to be in the range of 145 to 160 million, as compared to previous guidance of 140 to 169. Exfolio and net US product revenue expected to be in the range of 105 to 120 million, as compared to the previous guidance of 100 to 120 million. We are also lowering our expense guidance for the full year of 2024 as follows: R&D and SG&A expenses expected to be in the range of 250 to 265 million, which includes approximately 20 million of estimated noncash stock-based compensation expense, as compared to previous guidance of 260 to 280 million.

Mike: Specifically, since the beginning of last year, we've reduced our budget headcount by approximately 30%.

Mike: Our updated guidance ranges for the full year of 2024 are as follows. Total revenue expects to be in the range of $145 to $160 million, as compared to previous guidance of $140 to $160 million.

Mike: Expovio Net U.S. product revenue is expected to be in the range of $105 to $120 million as compared to the previous guidance of $100 to $120 million.

Mike: We are also lowering our expense guidance for the full year.

Mike: of 2024 as follows. R&D and SG&A expenses expected to be in the range of $250 to $265 million, which includes approximately $20 million of estimated non-cash, stock-based compensation expense as compared to previous guidance of $260 to $280 million.

Mike: And finally, we expect our existing cash, cash equivalent investments, as well as the revenue we expected journey from Exfolio and net product sales and other license revenues will be sufficient to fund our plan operations into G1 2026. Note that our cash runway does not include paying off the remaining 2025 convertible notes in our 25 million minimum liquidity covered into the new term. We expect our 2025 operating expenses to be lower than 2024 as we recognize the full-year benefits of our ongoing cost-saving initiatives.

Mike: And finally, we expect our existing cash, cash equivalents, and investments, as well as the revenue we expect to generate from ExpoViewNet product sales and other licensed revenues,

Mike: will be sufficient to fund our plan operations into Q1 2026.

Mike: Note that our cash runway does not include paying off the remaining 2025 convertible notes in our $25 million minimum liquidity covenant under the new term law. We expect our 2025 operating expenses to be lower than 2024 as we recognize the full-year benefits of our ongoing cost-saving initiatives.

Mike: In summary, we are focused on the advancement of our three phase three trials and driving commercial performance while continuing to be very diligent when allocating our resources. Now flip the slide 27 and turn the call over to Richard for some final thoughts.

Mike: In summary, we are focused on the advancement of our three phase three trials and driving commercial performance while continuing to be very diligent when allocating our resources. I'll now flip to slide 27 and turn the call over to Richard for some final thoughts. Richard?

Richard: Thank you, Mike. As you can see on slide 28, we have several meaningful milestones ahead of us in the near future. We believe our continued focus on disciplined capital allocation and expense management provides us with the cash runway to achieve these milestones.

Richard Paulson: Thank you, Mike.

Richard Paulson: As you can see on slide 28, we have several meaningful milestones ahead of us in the near future. We believe our continued focus on disciplined capital allocation and expense management provides us with cash runway to achieve these milestones. We're enthusiastic about our innovation and growth strategy, which provides us valuable optionality with our phase three clinical trials in my office and the metro cancer and multiple my mom. These trials have the potential to bring transformative benefits to patients and drive substantial progress for our company as a company. We will continue to stride towards unlocking style and XR's full potential as we execute in a disciplined manner and deliver on our next phase of growth.

Richard: Thank you, Mike. As you can see on slide 28, we have several meaningful milestones ahead of us in the near future. We believe our continued focus on disciplined capital allocation and expense management provides us with cash runway to achieve these milestones.

Richard: We are enthusiastic about our innovation and growth strategy, which provides us valuable optionality with our Phase III clinical trials in myofibrosis, endometrial cancer, and multiple myeloma.

Richard: These trials have the potential to bring transformative benefits to patients and drive substantial progress for our company.

Richard: As a company, we will continue to stride towards unlocking SalonXR's full potential as we execute in a disciplined manner and deliver on our next phase of growth.

Operator: 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.

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.

Operator: Thank you. Ladies and gentlemen, we will now begin the question and answer session.

Operator: 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 touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the following process, please press the star followed by the number two. If you are using a speaker phone, please lift the handset before pressing any key. One moment, please, for your first question.

Speaker Change: Thank you. Ladies and gentlemen, we will now begin the question and answer session.

Speaker Change: Should you have a question, please press the star followed by the number 1 on your touchtone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number 2.

Speaker Change: If you are using a speakerphone, please lift the handset before pressing any keys.

Peter Lawson: Our first question is from Peter Lawson from Bartlett.

Speaker Change: One moment, please, for your first question.

Speaker Change: Our first question is from Peter Lawson from Barclays.

Alex: Hey, good morning. This is Alex on for Peter. Thank you for taking our questions.

Speaker Change: Hey, good morning. This is Alex for Peter. Thank you for taking our questions.

Alex: I just wanted to I was wondering if you could expand a little bit on what is driving the change in timelines for the endometrial trial and the higher screen failure rates and beyond adding additional sides.

Alex: I just wanted to, I was wondering if you could expand a little bit on what is driving the change in timelines for the endometrial trial and the higher screen failure rates. And beyond adding additional sites, are there any other changes being implemented in the trial here?

Richard Rajma: Are there any other changes being implemented in the trial here? Yes, thanks, Alex. I'll turn to Rationary for that, and really I think she highlighted it at a high level. But to go into some more detail, when we look at kind of the warnings we have in the endometrial trial and what's happening and how we're addressing it.

Speaker Change: Thanks, Alex. I'll turn to Reshma for that and really, I think she highlighted it at a high level, but to go into some more detail when I look at kind of the learnings we have in the endometrial trial and what's happening and how we're addressing it. So I'll turn that to Reshma.

Reshma Rangwala: So I'll turn that to Rationary. Yeah, thank you. So I want to start off in the end of mutual space, just highlighting the data that we have observed with Selenexore in this unique population defined by their p53 status. You know, we first presented long-term data back in July of 2023. This was part of the ASCO Plenary Series. It was really important to note, especially from one of the moderators who described the data as truly unprecedented, and it underscores the benefit that Selenexore can achieve in this patient population defined by P53 status. Those data have only gotten stronger.

Reshma: Yeah, thank you.

Reshma: So I want to start off in the endometrial space just highlighting the data that we have observed with Selenexor in this unique population defined by their p53 status.

Reshma: You know, we first presented long-term data back in July of 2023. This was part of the ASCO plenary series. It was really important to note, especially from one of the moderators, who described the data as truly unprecedented, and it underscores...

Reshma: The benefit that Selenexor can achieve in this patient population defined by P53 status.

Reshma Rangwala: In fact, at ASCO, just a couple of months ago, Vicki Marker, who was at MSKCC, presented updated, the most recent updated data for Selenexore in this population. In those patients who are defined by both P53 wild type and PMMR status, their data now show an unprecedented 40-month median PFS. That 40 months actually exceeds the overall survival observed with the checkpoint inhibitors in that PMMR patient population. You are correct. You know, we are seeing challenges in our enrollment. One of the main drivers, and it's a recent observation, is this increase in screen failure rate, and it's very unique to a bio-marker incident driven trial.

Speaker Change: Those data have only gotten stronger. In fact, at ASCO, just a couple of months ago, Vicky Mocker, who is at MSKCC, presented updated, the most recent updated data, for Selenexor in this population.

Vicky Mocker: In those patients who are defined by both P53 wild-type and PMMR status, their data now show an unprecedented 40-month median PFS. That 40 months actually exceeds

Vicky Mocker: Unknown Speaker, the overall survival observed with the checkpoint inhibitors in that PMMR patient population.

Speaker Change: You are correct. You know, we are seeing challenges in our enrollment.

Speaker Change: One of the main drivers, and it's a recent observation, is this increase in screen failure rate. And it's very unique to a biomarker.

Reshma Rangwala: I say that because many of the physicians are submitting their biopsies relatively early during the chemotherapy process. That biopsy is evaluated for that P53 status. With that said, even if that biopsy is evaluated as P53 wild type, those patients need to complete months of chemotherapy. And during that time, we have been seeing that they can screen fail for a myriad of reasons, whether it's for lab reasons, scan reasons, they may need to have surgeries, or they may decide that they don't ultimately want to participate in a clinical trial. Those reasons contribute to that higher screen fail rate, and as such, we are actively looking at multiple initiatives, increase the total pool of patients that we can screen. The major initiative is going to be activating new sites, you know, in our current existing countries and potentially in new additional countries.

Speaker Change: I say that because many of the physicians are submitting their biopsies relatively early during the chemotherapy process. That biopsy is evaluated by foundation.

Speaker Change: for that p53 status. With that said, even if that biopsy is evaluated as p53 wild-type, those patients need to complete

Speaker Change: months of chemotherapy. And during that time, we have been seeing that they can screen fail for a myriad of reasons, whether it's for lab reasons, scan reasons, they may need to have surgeries.

Speaker Change: They may decide that they don't ultimately want to participate in a clinical trial. Those reasons contribute to that higher screen fail rate. And as such, we are actively looking at multiple initiatives.

Unknown Executive: So, as we continue to increase the total pool of patients that we can screen, the major initiative is going to be activating new sites, you know, in our current existing countries and potentially in new additional countries. Other initiatives that we are looking at are, you know, of course, doubling, doubling down on our medical affairs support, looking at outside vendors. We continue to partner very closely with the GOG and NGOT. Ultimately, we are committed to completing enrollment in this trial and updating everybody on top line results in early 2020.

Speaker Change: So as we increase the total pool of patients that we can screen, the major initiative is going to be activating new sites, you know, in our current existing countries and potentially in new additional countries.

Reshma Rangwala: Other initiatives that we are looking at is, you know, of course, you know, doubling, doubling down on our medical affairs support, looking at outside vendors.

Speaker Change: Other initiatives that we are looking at is, you know, of course, you know, doubling, doubling down on our medical affairs support, looking at outside vendors.

Reshma Rangwala: We continue to partner very closely with the GOG and got ultimately we are committed to completing enrollment of this trial and updating everybody on top line results in early 2026.

Speaker Change: We continue to partner very closely with the GOG and NGOT. Ultimately, we are committed to completing enrollment of this trial and updating everybody on top-line results in early 2026.

Alex: Great, that's helpful.

unknown: Thank you very much.

Speaker Change: Great. That's helpful. Thank you very much.

Alex: Thanks, Alex.

Maurice Raycroft: We'll be coming from Maurice Raycroft from Jeffery. Thanks for taking my questions. Maybe just a quick follow-up to the last one.

Operator: will be coming from Maury, Maury Raycroft from Jeff.

Speaker Change: Operator?

Speaker Change: We'll be coming from Maurice Raycroft from Jefferies.

Maury Raycroft: Hi. Thanks for taking my questions. Maybe just a quick follow-up to the last one. Are you saying anything more about how many new sites you anticipate opening and in what regions you plan on opening those sites in?

Maurice Raycroft: Are you saying anything more about how many new sites you anticipate opening and what regions you plan on opening those sites in? Yeah, thanks for the question, Maurice.

Reshma Rangwala: No, we're not providing any additional color on those details. Just, you know, primarily looking at, you know, opening up some new sites, you know, in our existing countries. And like I said, you know, potentially additional countries, and then continuing to support, you know, the many sites that have already been activated in our current trial. So I think those, you know, main focus, you know, really will enable that increased screening pool that we need to achieve to enable those top line results in the first in early 2026.

Speaker Change: Yeah, thanks for the question, Maureen. No, we're not providing any additional color on those details. Just, you know, primarily looking at, you know, opening up some new sites, you know, in our existing countries. And like I said, you know, potentially additional countries.

Speaker Change: And then continuing to support, you know, the many sites that have already been activated in our current trial. So I think those, you know, main...

Speaker Change: So this focus, you know, really will enable that increased screening pool that we need to achieve to enable those top-line results in the first, in early 2026.

Reshma Rangwala: Got it. And is there any way to potentially help mitigate the issue with the biopsy process? I guess can, can Karyopharm do anything to help on that front?

Speaker Change: Got it. And is there any way to potentially help mitigate the issue with the biopsy process? I guess can Karyopharm do anything to help on that front?

Reshma Rangwala: And then could part of the outcome of this lead to an enrichment of the P53 wild type PMR population, or, or how are you thinking about that? Sure, you know, I will send a biopsy. Process is already going very smoothly. You know, in endometrial cancer, molecular classification is really becoming the standard of care, both because physicians are evaluating the MMR status. As well as other biomarker classifications, including P53, Polly, et cetera. So physicians are really used to evaluating biopsies in the case of our clinical trial. They just submit that biopsy to Foundation Medicine. They process it very quickly.

Unknown Executive: Sure. You know, I would say the biopsy process is already going very smoothly. You know, in endometrial cancer, molecular classification is really becoming the standard of care, both because physicians are evaluating the MMR status, as well as other biomarker classifications, including P53, poly, etc. So, physicians are really used to evaluating biopsies. In the case of our clinical trial, they just submit that biopsy to Foundation Medicine, and they process it very quickly. And, you know, the results are turned around within a matter of days. The main driver specific to our trial is, again, that interval between when the biopsy is submitted and the month.

Speaker Change: Sure, you know, I will say the biopsy process is already going very smoothly, you know, in endometrial cancer, molecular classification is really becoming the standard of care both because physicians are evaluating the MMR status

Reshma Rangwala: And, you know, the results are turned around within a matter of days.

Reshma Rangwala: The main driver specific to our trial is again that interval between when the biopsy is submitted and the months of chemotherapy that they still need to complete, and that unfortunately is nothing. There's nothing that we can do to offset that process in terms of your second question. It's a good one. And I think, like naturally, we are going to see patients who are PMMR as well as P53 wild type based upon local testing, you know, disproportionately submitting tumors to SMI. So I think we will see that rate rise over time.

Maurice Raycroft: Okay. Thanks for taking my questions.

Maurice Raycroft: I'll hop back in the queue.

unknown: Thanks, Maureen.

Colleen Cassie: Next question will be coming from Colleen Cassie from Baird. Hi, good morning. Thanks for taking our questions.

Colleen Cassie: Among those enrolled for another question on the endometrial study.

Colleen Cassie: Can you comment on any sort of PFS metrics so far and how that's tracking risk or expectation and whether. And in rolling some of these PMMR Tp53 wild type patients might be pushing out the data as well, just given how, how long, how strong the C&O data.

Speaker Change: Among those enrolled, another question on the endometrial study, can you comment on any sort of PFS metrics so far and how that's tracking versus your expectation and whether kind of enrolling some of these PMMR.

Reshma Rangwala: Yeah, thanks for the question, Colleen. So no, you know, we do not have any insight in terms of the PSS results from this trial. It's a double-blinded trial. We also are very much blinded to the results across either one of these arms. So no insight there. We had an opportunity to report on multiple times. You know, that data just continues to get stronger, right? You know, in that large P53 wild type subgroup, we are now seeing a median PFS of 28.4 months. And I'll reiterate in that P53 wild type PMMR subgroup. Those data now demonstrate a median PFS of 40 months, truly unprecedented data, and really underscores the strength of the benefit that can be achieved with Selenex, or we've incorporated those PSS into our assumptions.

Speaker Change: Yeah.

Speaker Change: Results from this trial. It's a double-blinded trial.

Speaker Change: We also are very much blinded to the results across either one of these arms, so no insight there. You know, I think I'll just go back to the Sando data and that p53 wild-type subgroup that we've had an opportunity to report on multiple times.

Speaker Change: and really underscores the strength of the benefit that can be achieved with Selenexor.

Speaker Change: We've incorporated those PSS into our assumptions.

Reshma Rangwala: So, you know, we assume a very meaningful PSS benefit at the time of the top line results. And again, have already been incorporated into the projections that inform that early 2026 top line result readout. Got it.

Colleen Cassie: That's helpful. Thank you.

Colleen Cassie: And then on the screen failure rate, can you comment if the P53 wild type biomarker is roughly as prevalent as you thought it was so far in the screening process? Is it still roughly around 50%. Yeah, it is. It is, you know, putting nicely in that assumed rate of more than half of all patients.

Speaker Change: Got it. That's helpful. Thank you. And then on the screen failure rate, can you comment if the TP53 wild-type biomarker is...

Speaker Change: Roughly as prevalent as you thought it was so far in the screening processes, it's still roughly around 50%.

Speaker Change: Yeah, it is. It is. It's, you know, sitting nicely in that assumed rate of, you know, more than half of all patients.

Sohanya Cheng: Great. And then one commercial question, if I can, if so, honey, can you give it a sense of the duration of treatment for the pre and post T cell therapies you're seeing in the academic centers? Is it like a one month or, you know, maybe, maybe single digits, but just kind of help us get a range on that please. Yeah, thanks, Colin.

Speaker Change: Great and then one commercial question if I can. Sohanya, can you give us a sense of the duration of treatment for the pre and post T cell therapies you're seeing in the academic centers? Is it like a one month or you know maybe low single digits but just kind of help us give it get a range on that please.

Colleen Kusy: Yeah, thanks, Colleen. So we don't disclose the exact months of duration because we have to triangulate multiple data sources. It takes time for that to mature. However, take a step back and look at the trends overall. Obviously, we see a long-term trend since the launch of the drug in terms of increasing duration. The recent dynamics in the competitive landscape, obviously, with bridging and post-T cell therapies have obviously impacted duration, but this is a smaller proportion of our patients. The large majority of our patients remain in the early alliance, second, third, and fourth lines, and really, that helps to propel our duration.

Sohanya Cheng: So, we don't disclose exact months of duration because you have to triangulate multiple data sources; it takes time for that to mature. However, take a step back and look at trends overall. Obviously, we see a long-term trend since the launch of the drug in terms of increasing duration. The recent dynamics in the competitive landscape, obviously with bridging and post T cell therapies, have obviously impacted duration, but this is a small proportion of our patients. The large majority of our patients remain in the early, line 2nd, 3rd, and 4th lines, and really that helps to propel our duration up.

Speaker Change: Yeah, thanks, Colleen. So, we don't disclose exact months of duration because we have to triangulate multiple data sources. It takes time for that to mature. However, take a step back and look at trends overall. Obviously, we see a long-term trend since the launch of the drug in terms of increasing duration.

Speaker Change: The recent dynamics in the competitive landscape, obviously, with bridging and post T-cell therapies.

Speaker Change: have obviously impacted duration, but this is.

Speaker Change: A smaller proportion of our patients, the large majority of our patients remain in the early-aligned second, third, and fourth lines, and really that helps to propel our duration up.

Colleen Cassie: Great. Thanks for taking our questions.

Colleen Cassie: Thanks, Colin.

Speaker Change: Great. Thanks for taking our questions.

Brian Abraham: Next on the line is coming from Brian Abraham from RBC. Hi, good morning. Thanks for taking my questions.

Speaker Change: Next on the line is coming from Brian Abraham from RBC.

Unknown Attendee: Hi, good morning. Thanks for taking my questions. Maybe we can shift gears to myelofibrosis.

Brian Abraham: Maybe shifting gears to my low fibrosis. The Phase 3-034 study is based on some of the data you presented on slide 10 where you showed, you know, for quite robust benefits for cell and XR on top of Rucks, but relatively small number of patients.

Brian Abraham: Hi, good morning. Thanks for taking my questions. Maybe shifting gears to myelofibrosis.

Speaker Change: The Phase 3

Brian Abraham: 034 study. It is, you know, it's based on some of the data you presented on slide 10.

Speaker Change: where you showed quite robust benefits for Selenix on top of Rux, but in a relatively small number of patients. So I guess I'm curious, as the trial is continuing, if there may be any opportunities...

Brian Abraham: So I guess I'm curious as the trial is continuing, if there may be any opportunities to adjust the powering or design of the study based on the ongoing data or on regulatory outcomes from a collaborative, the late stage drug that's also in development.

Speaker Change: to adjust the powering or design of the study based on the ongoing data or on regulatory outcomes from Prolaborasiv, the late stage drug that's also in development. And then maybe secondarily on MF, it looked like

Reshma Rangwala: And then maybe 2ndarily on MF, it looked like the cell and XR monotherapy study was timeline was pushed out just a bit there, just wondering if you could tell us kind of how that study is going and the extent of the data we should be looking for now in the back in the end of this year or early next. Thanks for the question.

Speaker Change: The Selenix or monotherapy study was Timeline was pushed out just a bit there Just wondering if you could tell us kind of how that study is going and the extent of the data We should be looking for now in the back at the end of this year or early next. Thanks

Reshma Rangwala: So we remain really confident about myelofibrosis. You know, as you mentioned, the strength of the data are unparalleled. And the reason I say that is because yes, although we have a smaller cohort of patients in which we evaluated the efficacy with Selenex or plus Ruxilintnid, specifically a 79% SVR 35 rates and a 58% TSS 50 rate at week 24. It only builds upon the data that we have evaluated with not only Selenexor or about the combination, you know, underscore the preclinical data, the mechanistic data that really suggests that Selenexor an XPO1 inhibition is targeting both Jack and non-Jack pathways, as well as the, you know, the totality of the data that really suggests that when Selenexor is combined with Ruxolitinib, you can see added, if not synergistic effects layer on now the clinical data that have demonstrated monotherapy activity.

Speaker Change: Specifically, a 79% SVR35 rate and a 58% TSS50 rate at week 24, it only builds upon the data that we have evaluated with not only Selenexor but the combination.

Speaker Change: I'll underscore the preclinical data, the mechanistic data that really suggests that Selenexor and XPO1 inhibition is targeting both JAK and non-JAK pathways.

Speaker Change: Layer on now the clinical data that have demonstrated monotherapy activities. This goes back to the essential trial in that relapsed refractory

Reshma Rangwala: This goes back to the essential trial in that relapse refractory Jack, you know, previously exposed Jack population. And now, of course, you have to say is one data specifically evaluating Selenex or in combination with Ruxolitinib. So when I evaluate our opportunity and the strength of the data, it's really looking at all of those data sets that really inform the potential of Selenex or in mylohybrosis. What we also know from both patients as well as physicians is that the efficacy has to extend beyond just as SBR 35 and TSS 50 rates. I add that because we are also seeing very impressive durability.

Speaker Change: So when I evaluate our opportunity and the strength of the data, it's really looking at all of those data sets that really inform the potential of Selenecthor in myelofibrosis.

Speaker Change: What we also know from both patients as well as physicians is that the efficacy has to extend beyond just those SVR35 and TSS50 rates. I add that because we are also seeing very impressive durability. At the time of the most recent data cutoff, none of the patients had actually progressed either from an SVR35 standpoint or a TSS50. So what we are seeing is remarkable SVR35 and TSS50 rates as well as the corresponding durability that extend well beyond that week 24 time point.

Reshma Rangwala: At the time of the most recent data cutoff, none of the patients had actually progressed either from an SBR 35 standpoint or TSS 50. So what we are seeing is remarkable SBR 35 and TSS 50 rates, as well as the corresponding durability that extends well beyond that week 24 time point.

Reshma Rangwala: Lastly, I'll mention in terms of O44. Yes, we did push out the timelines a little bit. Now we are looking at, you know, end of 24, beginning of 25. It's a smaller patient population, so these are still Jack and I use patients. However, their plate lit count needs to be within that 50 to 100. So it is a smaller population is compared to that patient population in rolling in the phase three. Still lots of enthusiasm, and we look forward to providing data from that study shortly.

Speaker Change: Lastly, I'll mention in terms of 044, yes, we did push out the timelines a little bit. Now we are looking at, you know, end of 24, beginning of 25.

Unknown Attendee: I guess I was thinking if the effect size in Phase 3 was maybe even more robust than what you had seen in Phase 2, if there might be an opportunity to maintain powering but cut the trial size down a bit and accelerate timelines there.

Brian Abraham: That's really helpful. Thank you.

Brian Abraham: I guess I was thinking if the effect size in the phase three was maybe even more robust than what you had seen in the phase two, if there might be an opportunity to maintain powering but cut the trial size down a bit and accelerate timelines there. Yeah, it's a good question. I mean, we are completely blinded to the results.

Unknown Executive: Yeah, it's a good question. I mean, we are completely blinded to the results, so that's not something that we can do. But, you know, like all of our phase threes, we do have an independent DMC that is evaluating the results. And based upon their assessment, we'll certainly consider whether that opportunity exists for the trial.

Reshma Rangwala: So that's not something that we can do, but, you know, like all of our phase threes, we do have an independent DMC that is evaluating the results, and based upon their assessment, will certainly consider it's that opportunity exists for the trial. Thanks.

Speaker Change: Yeah, it's a good question. I mean, we are completely blinded to the results.

Speaker Change: Thanks.

Operator: Ladies and gentlemen, if you have any questions, please press star followed by the number one on your touch-tone phone. You will hear a prompt that your hand has been raised. Again, if you have any question, please press the star followed by the number one on your touchstone phone, and you will hear a prompt that your hand has been raised.

Speaker Change: Ladies and gentlemen, if you have any questions, please press star followed by the number one on your touchtone phone. You will hear a prompt that your hand has been raised.

Operator: Again, if you have any questions, please press the star followed by the number one on your touchtone phone, and you will hear a prompt that your hand has been raised.

Speaker Change: Again, if you have any questions, please press the star followed by the number one on your touchtone phone, and you will hear a prompt that your hand has been raised.

Jonathan Chang: Last question on the line will be coming from Jonathan Chang from Learing Parkers. Great.

Speaker Change: Last question on the line will be coming from Jonathan Chang from Leering Partners.

Unknown Attendee: Great. Hi guys, this is Matt Ong for Jonathan.

Matt: Hi guys, this is Matt on for Jonathan. Thanks for taking my question.

Matt: Just looking at some of the details of the cash run away, including the liquidity cabinet, et cetera, how often are you that you have sufficient cash from where to get to the updated end of mutual cancer top line readout.

Matt Ong: Thanks for taking my question. Just looking at some of the details of the cash runway, including the liquidity covenant, etc., how confident are you that you have sufficient cash runway to get to the updated endometrial cancer top-line readout? And how should we be thinking about the monetization of assets such as KPT-9274 as it relates to making the timeline work? And lastly, can you comment on whether there are other programs in the pipeline with similar potential for outlicensing such as 9274? Thank you.

Speaker Change: Great. Hi, guys. This is Matt on for Jonathan. Thanks for taking my question.

Mike: And how should we think about the monetization of assets such as KPT 9274 as it relates to making the timeline work?

Mike: And lastly, can you comment if there are other programs in the pipeline with similar potential for out-licensing such as 9274?

Speaker Change: And lastly, can you comment if there are other programs in the pipeline with similar potential for out licensing such as 9274? Thank you very much.

Mike: Thank you very much.

Mike: Thanks for the question. I might talk to the first part, and then I can jump into the second and third question. So reminder, our previous cash run was into the end of 2025. We've tightened our 2024 OptX guidance to be 250 to 265 million, which includes 20 million of stock comp, which is down from 260 to 280 million previously. And you know, part of that lowering expenses was that was the plan resizing with our EM 29 trial and just to continue discipline on operating costs. Yes, we realized the importance of extending that cash runway. We have three pivotal Read Us.

Speaker Change: Yeah, thanks for the questions. I'll let Mike talk to the first part and then I can jump into the second and third question. Sure. So, reminder, our previous task runner was into the end of 2025. We've tightened our 2024 OPEX guidance.

Speaker Change: to be $250 to $265 million, which includes.

Mike: 20 million of stock up, which is down from 260 to 280 million.

Mike: was the plan resizing with our EM29 trial and just to continue discipline on operating costs. Yes, we realized the importance of extending that cash runway. We have three pivotal readouts. First one is myeloma, which is in the first half of 2025.

Mike: First one is my Loma, which is in the first half of 2025. Second one is my Leprosis in the second half of 2025 and the third in an endometrial and early 2026. So putting all those together, our cash run, I guess, is into the early early 20, so excluding the convert that we have to do in October 2025.

Mike: Myelofibrosis in the second half of 2025, and the third in endometrial in early 2026. So, putting all of those together, our cash funding gets us into the early 2026, excluding the convert that we have to do in October 2025.

Mike: Yeah, and I think if we build on, you know, as you mentioned, talking about KPT-9274, you know, it's a novel first-in-class oral small molecule, dual inhibitor of pack for an amputee that was discovered by Carry On Farm. And is part of our early stage programs. So obviously, recently, as we, you know, announced today, we were able to receive both rare pediatric disease designation and orphan drug disease as a nation. So I think a really strong opportunity where we're going to be looking to partner out license, you know, that asset to make sure that we can recognize the full value of it and help to work to bring to patients or enable someone else for work to bring to patients.

Speaker Change: Yeah, and I think if we build on, you know, as you mentioned talking about KPT-9274, you know, it's a novel first-in-class oral small molecule dual inhibitor of APAC4 and NAMPT that was discovered by Karyopharm.

Speaker Change: and is part of our early stage programs. So obviously recently, as we, you know, announced today, we were able to receive

Speaker Change: Both Rare Pediatric Disease Designation and Orphan Drug Disease Designation, so I think a really strong opportunity where we're going to be looking to partner out license, you know, that asset to make sure that we can recognize the full value of it and help to work to bring it to patients or enable someone else.

Mike: So that's a strong opportunity for us, obviously, with some strong value behind it, given those designations and given the high unmet need in both Ravda, sarcoma and Ewing sarcoma. Also, I think as we've talked to before, we have Elton XOR, which is our second novel sign compound, which we will look at a potential partnerships in terms of that asset across the globe. Right now, it's currently partner just in Asia Pac. So that gives us, you know, optionality to look at moving forward, and then yes, we have a couple other, you know, assets within the pipeline that we're always opportunistic to see what's the best way to recognize value from those assets.

Speaker Change: I work to bring to patients, so that's a strong opportunity for us, obviously, with some strong value behind it, given those designations and given the high unmet need in both rhabdo-sarcoma and Ewing's sarcoma.

Unknown Executive: Also, as we've talked about before, we have Eltanexor, which is our second novel sign compound that we will look at potential partnerships in terms of

Speaker Change: Also, I think as we've talked to before, we have Eltenexor, which is our second novel sign compound, which we will look at potential partnerships in terms of

Speaker Change: that asset across the globe. Right now it's currently partnered just in Asia-PAC.

Speaker Change: So that gives us, you know, optionality to look at moving forward.

Speaker Change: And then, yes, we have a couple other, you know, assets within the pipeline that

Mike: So, you know, I think some good optionality in terms of our BD area and obviously with KP9274 and the recognition and the areas who've just been recognized by the FDA, I think that adds, you know, significant value and looking to recognize that value.

Speaker Change: We're always opportunistic to see what's the best way to recognize value from those assets. So, you know, I think some good optionality in terms of...

Speaker Change: RBD area and obviously with KPC-9274 and the recognition and the areas that have just been recognized by the FDA, I think that adds significant value and looking to recognize that value.

Matt: Thanks so much. Thanks.

Operator: There are no further questions at this time.

Speaker Change: Got it. Thank you so much.

Richard Paulson: I'd now like to turn the poll back over to Mr. Richard Paulson for final closing comments. Thank you, operator, and thank you, everyone, for joining us on today's call. We are focused on accelerating the momentum as we look to deliver on our next phase of growth, and our people continue to strive each day for patients with high-end met needs as we work to generate value for patients and shareholders.

Speaker Change: There are no further questions at this time. I'd now like to turn the call back over to Mr. Richard Paulson for final closing comments.

Richard Paulson: Thank you, Operator, and thank you, everyone, for joining us on today's call. You know, we are focused on accelerating the momentum as we look to deliver on our next phase of growth and our people continue to strive each day for patients with high-end MET needs as we work to generate value for patients and shareholders. So thank you for joining again and have a great day, everyone.

Operator: So thank you for joining again, and have a great day everyone.

Operator: Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.

Speaker Change: Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines. You may all have a good one.

Give me all. Have a good one.

Operator: Goodbye.