Karyopharm Therapeutics Inc. · NASDAQ:KPTI

Karyopharm Therapeutics — Technical Presentation (March 2026)

23 slides from Karyopharm Therapeutics's technical presentation, Mar 24, 2026

  1. Slide 1: Phase 3 SENTRY Topline Results

    Exhibit 99.2 Phase 3 SENTRY Topline Results March 24, 2026

  2. Slide 2: On Today's Call

    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 Inve

  3. Slide 3: Forward-looking Statements and Other Important Information

    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

  4. Slide 4: Opening Remarks

    OPENING REMARKS Richard Paulson President and Chief Executive Officer ©2026 KARYOPHARM THERAPEUTICS INC.

  5. Slide 5: Encouraging Profile Observed with Differentiated Mechanism of XPO1 Inhibition and Ruxolitinib

    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

  6. Slide 6: Phase 3 SENTRY Topline Results

    PHASE 3 SENTRY TOPLINE RESULTS Reshma Rangwala, MD, PhD Chief Medical Officer and Head of Research ©2026 KARYOPHARM THERAPEUTICS INC.

  7. Slide 7: XPO1 Inhibition is a Multifaceted Approach to Inhibiting the Drivers of Myelofibrosis

    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

  8. Slide 8: Phase 3 SENTRY Trial of Selinexor in Combination with Ruxolitinib in JAKi-Naïve Myelofibrosis

    * 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

  9. Slide 9: Selinexor plus Ruxolitinib Resulted in Superior SVR35 Rates at Week 24

    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

  10. Slide 10: Rapid and Sustained Improvement in SVR35 Rates Relative to Ruxolitinib Alone

    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 a

  11. Slide 11: Rapid, Deep and Sustained Spleen Reduction Relative to Ruxolitinib Alone

    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. Slide 12: Symptom Benefit at Week 24 Comparable Across the Two Arms

    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

  13. Slide 13: Promising Overall Survival Signal with >50% Reduction in Risk of Death

    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

  14. Slide 14: VAF Reduction in JAK2, CALR and MPL Driver Mutations

    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

  15. Slide 15: Manageable Safety and Tolerability Profile

    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 indi

  16. Slide 16: Encouraging Profile Observed with the Differentiated Mechanism of XPO1 Inhibition

    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

  17. Slide 17: Treatment Landscape

    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

  18. Slide 18: The SENTRY Results Matter in Myelofibrosis Given Limited Treatment Options

    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 Produ

  19. Slide 19: Established Data Suggest Spleen Response Positively Impacts Overall Survival

    Established Data from Other Trials Suggest Achieving and Maintaining Spleen Response Positively Impacts Overall Survival Coltro et. al Cancer Medicine 2023 19 ©2026 KARYOPHARM THERAPEUTICS INC.

  20. Slide 20: NCCN Myelofibrosis Management and Treatment Guidelines

    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 • Cli

  21. Slide 21: Summary

    SUMMARY Richard Paulson President and Chief Executive Officer ©2026 KARYOPHARM THERAPEUTICS INC.

  22. Slide 22: Deeply Committed to Advancing Selinexor in Myelofibrosis

    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

  23. Slide 23: Our sincere thanks

    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.

Karyopharm Therapeutics — Technical Presentation (March 2026) on 6ix