EX-99.2

EX-99.2 7 d125009dex992.htm EX-99.2 EX-99.2

Exhibit 99.2 Phase 3 SENTRY Topline Results March 24, 2026

On Today’s Call Welcome Brendan Strong, SVP, Investor Relations Opening Remarks Richard Paulson, President and Chief Executive Officer Phase 3 SENTRY Topline Results Dr. Reshma Rangwala, Chief Medical Officer and Head of Research Myelofibrosis Treatment Landscape Dr. John Mascarenhas, Principal Investigator of Phase 3 SENTRY Trial; Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders Summary Richard Paulson, President and Chief Executive Officer Q&A Session 2 ©2026 KARYOPHARM THERAPEUTICS INC.

Forward-looking Statements and Other Important Information This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm’s beliefs about the ability of selinexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, diffuse large B-cell lymphoma and other diseases; expectations with respect to the clinical development plans and potential regulatory submissions for selinexor; the market opportunity and annual peak revenue opportunities for selinexor; and expectations regarding the timing, presentation and publication of additional data from the Phase 3 SENTRY trial. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm’s drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm’s drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm’s drug candidate portfolio will result in stock price appreciation. Management’s expectations and, therefore, any forward-looking statements in this presentation could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm’s drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm’s drug candidates that receive regulatory approval; Karyopharm's results of clinical and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; substantial doubt exists regarding Karyopharm’s ability to continue as a going concern; development or regulatory approval of drug candidates by Karyopharm’s competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm’s ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption Risk Factors in Karyopharm’s Annual Report on Form 10-K for the year ended December 31, 2025, which was filed with the Securities and Exchange Commission (SEC) on February 13, 2026, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this presentation speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Karyopharm regularly uses its website to post information regarding its business, drug development programs and governance. Karyopharm encourages investors to use www.karyopharm.com, particularly the information in the section entitled “Investors,” as a source of information about Karyopharm. References to www.karyopharm.com in this presentation are not intended to, nor shall they be deemed to, incorporate information on www.karyopharm.com into this presentation by reference. Other than the currently approved indications of XPOVIO, selinexor is an investigational drug that has not been approved by the FDA or any other regulatory agency, and the safety and efficacy of this drugs has not been established by any agency. ® ® XPOVIO (selinexor) and NEXPOVIO (selinexor) are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this presentation are the property of their respective owners. All rights reserved. 3 ©2026 KARYOPHARM THERAPEUTICS INC.

Encouraging Profile Observed with the Differentiated Mechanism of XPO1 Inhibition and Ruxolitinib with Potential to Improve Outcomes for Patients Co-Primary Endpoint Co-Primary Endpoint Secondary Endpoint Statistically Significant Not Statistically Significant Nominally Significant Promising Signal of Rapid, Near-Doubling Similar Improvement Overall Survival and Sustained SVR35 in Symptoms Rates Compared to Compared to Compared to Ruxolitinib Ruxolitinib Ruxolitinib Pre-Specified Exploratory Endpoint VAF Reduction Suggests Evidence of Potential Disease Modification Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. 5 ©2026 KARYOPHARM THERAPEUTICS INC.

XPO1 Inhibition is a Multifaceted Approach to Inhibiting the Drivers of 1-9 Myelofibrosis SEL ↓ Clonal cell division XPO-1 ↓ Splenomegaly Inflammatory c-myc cytokine / chemokine ↓ Variant Allele Frequency c-myc (VAF) Oncogene XPO-1 IκBα Oncogene mRNA ↓ NFκB activity ↓ Cytopenias, fibrosis, SEL Tumor suppressor protein constitutional symptoms IκBα IκBα JAK-STAT IL-6 JAK2 signaling SEL Selinexor JAKi ↑ Apoptosis JAKi JAK inhibitor ↓ Variant Allele Frequency (VAF) XPO-1 p53 p53 SEL NUCLEUS CYTOPLASM 1. Yan D et al. Clin Cancer Res. 2019;25(7):2323-2335. 2. Kashyap T et al. Oncotarget. 2016;7(48):78883-78895. 3. Walker CJ et al. Blood. 2013;122(17):3034-3044. 4. Cheng Y et al. Mol Cancer Ther. 2014;13(3): 675-686. 5. Argueta C et al. Oncotarget. 2018;9(39);25529-25544. 6. Gandhi UH et al. Clin Lymphoma Myeloma Leukemia. 2018;18(5):335-345. 7. Garg M et al. Oncotarget. 2017;8(5):7521-7532. 8. Tan M et al. Am J Physiol Renal Physiol. 2014;307(11): F1179-1186. 9. Turner JG et al. Oncotarget. 2016;7(48):78896-78909. 7 ©2026 KARYOPHARM THERAPEUTICS INC.

* Phase 3 SENTRY Trial (XPORT-MF-034 ) of Selinexor in Combination with Ruxolitinib in JAKi-Naïve Myelofibrosis a Ruxolitinib BID + Primary Endpoints Selinexor 60 mg QW JAKi-naïve Patients (tested sequentially) (28-day cycle) with Myelofibrosis R c SVR35 week 24 2:1 (N=353) + a Ruxolitinib BID + Abs-TSS 9 Plt >100 x 10 /L b,c,d Placebo week 24 *NCT04562389 Select Secondary and e Exploratory Endpoints Randomization stratified by: • Progression free survival • Dynamic International Prognostic Scoring System (DIPSS) risk category intermediate -1 • Overall survival vs. intermediate -2 or high-risk • Hemoglobin stabilization 3 3 • Spleen volume <1800 cm vs. >1800 cm by MRI/CT scan • Variant allele frequency (VAF) 9 9 reduction • Baseline platelet counts 100-200 x 10 / L vs. >200 x 10 /L • Bone marrow fibrosis improvement • Changes in cytokine levels Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. a. Ruxolitinib dose based on platelet count per prescribing information. b. Evaluated by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. c. Both endpoints are powered at >80%; the assumptions for SVR35 is 40% for ruxolitinib and 70% for selinexor + ruxolitinib; assumptions for Abs-TSS are a >4-point delta and a standard deviation of 12 for both arms. d. Active symptoms of myelofibrosis as determined by presence of at least 2 symptoms using the MFSAF version 4.0. e. A sample of secondary and exploratory endpoints to be evaluated. Abs-TSS; absolute TSS; BID: Twice daily; JAKi, janus kinase inhibitors; Plt: Platelet; QW: Once weekly; SVR35: Spleen volume reduction ≥ 35% 8 ©2026 KARYOPHARM THERAPEUTICS INC.

Selinexor plus Ruxolitinib Resulted in Superior SVR35 Rates at Week 24 Selinexor + Placebo + Ruxolitinib Ruxolitinib (N = 235) (N = 118) Spleen Volume Reduction SVR35 at Week 24, n (%) 117 (49.8) 33 (28.0) Exact 95% CI (43.2, 56.4) (20.1, 37.0) 21.82 Difference in SVR35 at Week 24 (%) Superior SVR35 at week 24 (Selinexor vs. Placebo) (11.50, 32.14) 95% CI of 50%, a near doubling compared to 28% with Cochran-Mantel-Haenszel Test (Selinexor vs. Placebo) ruxolitinib monotherapy Odds Ratio (95% CI) 2.58 (1.60, 4.17) (p<0.0001) One Sided P-value <.0001 Data Cutoff Date: 2026-02-20 CI=Confidence Interval; SVR35=Spleen Volume Reduction of >=35% Note: SVR35 at Week 24 is defined as proportion of patients with a >=35% reduction in spleen volume from baseline to Week 24, as measured by MRI or CT scan by Investigator assessment. Note: Cochran-Mantel-Haenszel test is stratified by randomization factors. Note: n is the number of patients with SVR assessments available. Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. 9 ©2026 KARYOPHARM THERAPEUTICS INC.

Rapid and Sustained Improvement in SVR35 Rates Observed with the Combination Relative to Ruxolitinib Alone Selinexor + Placebo + Ruxolitinib Ruxolitinib (N = 235) (N = 118) Spleen Volume Reduction SVR35 at Week 12, n (%) 116 (49.4) 24 (20.3) SVR35 at Week 24, n (%) 117 (49.8) 33 (28.0) Rapid SVR35 at week 12 of Patients Who Completed Week 36 or 207 100 Discontinued Prior to Week 36 49% compared to 20% with SVR35 at Week 36, n (%) [1] 97 (46.9) 23 (23.0) ruxolitinib monotherapy SVR35 at Any Timepoint, n (%) 159 (67.7) 53 (44.9) Exact 95% CI (61.3, 73.6) (35.7, 54.3) Sustained SVR35 at week 36 Cochran-Mantel-Haenszel Test of 47% compared to 23% with (Selinexor vs. Placebo) Odds Ratio (95% CI) 2.59 (1.64, 4.10) ruxolitinib monotherapy Nominal One Sided P-value <.0001 Data Cutoff Date: 2026-02-20 CI=Confidence Interval; SVR35=Spleen Volume Reduction of >=35% Note: SVR35 at Week 12 and 24 allows +/- 21-day window. SVR35 at Week 36 and 48 allows +/- 28-day window. Note: SVR35 at any timepoint is defined as Selinexor has not been approved by the U.S. FDA or proportion of patients with a >=35% reduction in spleen volume from baseline to any post-baseline assessments regardless of visit window before new anti-MF therapy or disease progression. Note: Cochran-Mantel-Haenszel test is stratified by randomization factors. any other regulatory authority for use in myelofibrosis. [1] Denominator is the number of patients who completed the spleen assessment or discontinued the study prior to the specific timepoint. 10 ©2026 KARYOPHARM THERAPEUTICS INC.

Rapid, Deep and Sustained Spleen Reduction Observed with the Combination Relative to Ruxolitinib Alone 10 0 -10 -20 -30 -40 -50 -60 -70 Seli Sene linxo exr o+ r + R R ux ux oli olt itiini nib b P Plla ac ce eb boo ++ R R uux xooli litin tiinib b -80 235 118 199 102 186 98 134 76 94 53 Baseline Week 12 Week 24 Week 36 Week 48 Not all patients have been followed beyond week 24 Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. Data Cutoff Date: 2026-02-20 11 ©2026 KARYOPHARM THERAPEUTICS INC. Mean(+/- SD)

Symptom Benefit at Week 24 was Comparable Across the Two Arms with Similar Symptom Improvement Relative to Baseline Selinexor + Placebo + Ruxolitinib Ruxolitinib (N = 235) (N = 118) Baseline Symptom Improvement n 235 117 Median 21.71 19.57 Mean 22.74 (11.877) 22.23 (13.031) Mean (STD) 2.1 , 53.9 3.0 , 58.3 Similar levels of absolute TSS improvement from Week 24 Adjusted Absolute Mean Change -9.89 -10.86 baseline in the selinexor from Baseline (95% CI) (-11.19, -8.59) (-12.58, -9.14) Adjusted Mean Difference 0.97 plus ruxolitinib arm (Selinexor vs. Placebo) (95% CI) (-1.07, 3.02) compared to ruxolitinib One-sided P-value 0.8246 Data Cutoff Date: 2026-02-20 CI=Confidence Interval; TSS=Total Symptom Score These differences were not statistically significant Note: TSS is the sum of the 6 individual symptom scores included in the MFSAF v4.0, excluding fatigue. Each individual symptom score is on the 0-10 scale, and the TSS ranges from 0 to 60. A higher TSS indicates a higher disease burden and thus a worse outcome. Note: Adjusted absolute mean change from baseline, adjusted mean difference, 95% CI and p-value are based upon mixed- Selinexor has not been approved by the U.S. FDA or effects model for repeated measures (MMRM) adjusted for randomization stratification factors, sex and baseline TSS. any other regulatory authority for use in myelofibrosis. Note: n is the number of patients with TSS available. 12 ©2026 KARYOPHARM THERAPEUTICS INC.

Promising Overall Survival Signal was Observed with a >50% Reduction in Risk of Death The Company intends to continue to follow OS to maturity to further evaluate this signal Selinexor + Placebo + Ruxolitinib Ruxolitinib Overall Survival (OS) is a pre- (N = 235) (N = 118) Patients with Events, n 11 of 235 12 of 118 specified secondary endpoint Percentage (%) 4.7 10.2 Hazard ratio of 0.43 and a nominal Median OS Follow-up Time (Months) [1] 11.56 12.58 p-value of 0.0222 95% CI (10.71, 13.01) (10.61, 13.93) Overall Survival - Stratified Test [2] Hazard Ratio (95% CI) [3] 0.43 (0.19, 1.00) One-Sided Nominal P-value (log- Post-hoc landmark analyses at 0.0222 rank) weeks 12 and 24 suggest Data Cutoff Date: 2026-02-20 SVR35 may predict CI=Confidence Interval Note: Overall Survival (OS) is defined as the duration from date of randomization to date of death due to any cause. overall survival [1] Based on reverse Kaplan-Meier method by swapping the censoring status. [2] Stratified by the randomization stratification factors. [3] Based on Cox Proportional Hazard model with Efron's method of handling ties. Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. 13 ©2026 KARYOPHARM THERAPEUTICS INC.

Variant Allele Frequency (VAF) Reduction in JAK2, CALR and MPL Driver 1-3 Mutations is Evidence of Potential Disease Modification VAF reduction was a prespecified exploratory endpoint The proportion of patients who achieved a ≥20% VAF reduction at week 24 was greater with selinexor plus ruxolitinib compared to ruxolitinib alone 32% 24% VS 4 Selinexor + Ruxolitinib Ruxolitinib (n=92 ) 4 Combination (n=169 ) Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. Data Cutoff Date: 2026-02-20 1. Ross et. al Blood 2024. 2. Guglielmelli et. al AM J HEMATOL 2024 3. Deininger et al Blood 2015. 4. n= patients with VAF analysis at baseline and week 24 14 ©2026 KARYOPHARM THERAPEUTICS INC.

Manageable Safety and Tolerability Profile Selinexor + Placebo + Ruxolitinib Ruxolitinib (N = 234) (N = 116) n (%) n (%) Safety and tolerability is consistent 1 All Grade TEAEs with the known profile of selinexor Thrombocytopenia 139 (59.4) 50 (43.1) Anaemia 134 (57.3) 67 (57.8) and ruxolitinib individually Nausea 134 (57.3) 20 (17.2) Constipation 74 (31.6) 42 (36.2) Neutropenia 63 (26.9) 10 (8.6) Grade 3+ TEAEs 164 (70.1) 58 (50.0) TEAEs Leading to Study Treatment 34 (14.5) 10 (8.6) Discontinuation No new safety signals identified The confirmed leukemic transformation rate was identical across both treatment arms at 1.7%. Selinexor is an FDA approved drug in certain indications, including multiple myeloma, and has been used to treat more than 30,000 patients. Data Cutoff Date: 2026-02-20 Note: Adverse events are coded using MedDRA version 28.1. Multiple occurrences of the same preferred term will only be Selinexor has not been approved by the U.S. FDA or counted once for each patient. any other regulatory authority for use in myelofibrosis. 1. Five most common TEAEs in the combination arm 15 ©2026 KARYOPHARM THERAPEUTICS INC.

Encouraging Profile Observed with the Differentiated Mechanism of XPO1 Inhibition and Ruxolitinib with Potential to Improve Outcomes for Patients Rapid, Near-Doubling and Sustained SVR35 Rates Similar Improvement in Symptoms Relative to Ruxolitinib Promising Signal in Overall Survival VAF Reduction Suggests Evidence of Potential Disease Modification Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. 16 ©2026 KARYOPHARM THERAPEUTICS INC.

TREATMENT LANDSCAPE John Mascarenhas, M.D. Principal Investigator of Phase 3 SENTRY trial; Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders The views expressed today by Dr. Mascarenhas are solely his views and are not necessarily shared by Karyopharm Therapeutics Inc. ©2026 KARYOPHARM THERAPEUTICS INC.

The SENTRY Results Matter in Myelofibrosis Given the Limited Treatment Options and Poor Prognosis Opportunity to Improve Outcomes Four Hallmarks of Myelofibrosis 1 Low rates of SVR35 Enlarged 5 Spleen No novel mechanisms beyond JAK inhibitors Constitutional Abnormal Blood 2,6,7 3 Symptoms Cell Production Median survival of patients with intermediate-to-high risk 4,8 myelofibrosis is 4 to 5 years Bone Marrow 3 Fibrosis Minimal evidence of disease 9 modification 1. Ruxolitinib-alone arms of SIMPLIFY-1 Study, 2017; MANIFEST-2 Study,ASH 2023; and Transform-1 Study ASH 2023 2. Tefferi A. Am J Hematol. 2023;98:801-821. 3. O’Sullivan JM, Harrison CN. Clin Adv Hematol Oncol. 2018;16(2):121-131. 4. Passamonti F, et al. Blood. 2010;115(9):1703-1708. 5. Vannuchi A, et al. Haematologica. 2015;100(9):1139-1145. 6. Mesa R, et al. Leuk Res. 2009;33(9):1199-1203. 7. Mitra D, et al. Cancer Med. 2013;2(6):889-898. 8. Data on File; internal analysis of published MF trial data. 9. Pemmaraju et. al Cancer 2022. 18 ©2026 KARYOPHARM THERAPEUTICS INC.

NCCN Myelofibrosis Management and Treatment Guidelines Higher-Risk MF Lower-Risk MF 9 9 Asymptomatic Symptomatic Anemia PLT < 50x10 /L PLT ≥ 50x10 /L Based on spleen and Not transplant Not transplant • Clinical trial symptoms candidate or not Transplant candidate candidate or not • Observation • Clinical trial • Clinical trial feasible feasible • Ruxolitinib • Momelotinib • Peginterferon • Ruxolitinib alfa-2a • Luspatercept • Hydroxyurea • Danazol • Pacritinib • ESA • Clinical Trial • Clinical trial • Momelotinib • Lenalidomide/pred Allogenic HCT • Ruxolitinib • Pacritinib nisone • Fedratinib • Momelotinib • Pacritinib • Pacritinib • JAKi combination • Momelotinib Higher-risk MF typically has Lower-risk MF typically lacks or has minimal signs and several signs and symptoms symptoms and a longer median survival and a shorter median survival NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 1.2026. Accessed March 13, 2026. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf 20 ©2026 KARYOPHARM THERAPEUTICS INC.

Deeply Committed to Advancing the Development of Selinexor as a Potential Therapy in Myelofibrosis SENTRY Supports High Unmet Need Engage with FDA Selinexor’s with One on the Totality of Potential Role in Approved Class of the Data and sNDA Myelofibrosis Therapy Filing Plan Present SENTRY results at medical meeting and submit manuscript for publication Potential compendia inclusion in the second half of 2026 Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. 22 ©2026 KARYOPHARM THERAPEUTICS INC.

Our sincere thanks… … to patients, caregivers, investigators and clinical trial sites for their participation in SENTRY and to the Karyopharm team for their commitment to advancing innovative therapies for patients with significant unmet medical needs.