Karyopharm Therapeutics Inc. · NASDAQ:KPTI

Karyopharm Therapeutics — Investor Presentation (May 2026)

59 slides from Karyopharm Therapeutics's investor presentation, May 2026

  1. Slide 1: Corporate Presentation May 2026

    Corporate Presentation May 2026

  2. Slide 2: 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 guidance on its 2026 total revenue, 2026 U

  3. Slide 3: 2026 is a Transformative Year for Karyopharm with Major Phase 3 Readouts

    2026 is a Transformative Year for Karyopharm with Major Phase 3 Readouts XPOVIO® (selinexor) has a Novel & Differentiated MoA Growing Global Demand Multi-Billion Dollar that has the Potential to for XPOVIO/NEXPOVIO® U.S. Myelofibrosis and Treat Various Cancers1 (selinexor); Now Approved in Endometri

  4. Slide 4: Topline Data from Two Potentially Transformative Phase 3 Trials in 2026

    Topline Data from Two Potentially Transformative Phase 3 Trials in 2026 Indication Early Stage Mid Stage Late Stage Commercial Multiple myeloma (penta-refractory) w/dexamethasone Multiple myeloma (2L+) w/bortezomib + dexamethasone Myelofibrosis (JAKi naïve) Topline Data Announced March 2026 SELINEXO

  5. Slide 5: Selinexor and Eltanexor (XPO1 Inhibitors)

    Nucleus Nuclear pore Selinexor and Eltanexor (XPO1 complex Inhibitors) selectively inhibit the export XPO1 Protein cargoes: e.g., tumor of multiple macromolecules from the suppressor proteins and growth regulators like p53, p27, or FOXO nucleus to the cytoplasm family proteins1,2 RAN-GTP 1.Increases

  6. Slide 6: Executing on Potentially Transformative Opportunities

    Executing on Potentially Transformative Opportunities Phase 3 Phase 3 Commercialization SENTRY XPORT-EC-042 Capabilities Engage with the FDA Enrollment Completed Existing Capabilities to Support Future Late-Breaking Oral Topline Results Expected Launches Presentation at ASCO mid-2026 Potential Compe

  7. Slide 7: Phase 3 SENTRY Topline Results in Myelofibrosis

    PHASE 3 SENTRY TOPLINE RESULTS IN MYELOFIBROSIS ©2026 KARYOPHARM THERAPEUTICS INC.

  8. Slide 8: Encouraging Profile Observed with 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 Rapid, Near-Doubl

  9. Slide 9: The SENTRY Results Matter in Myelofibrosis

    The SENTRY Results Matter in Myelofibrosis Given the Limited Treatment Options and Poor Prognosis Opportunity to Improve Outcomes Four Hallmarks of Myelofibrosis Low rates of SVR351 Enlarged Spleen5 No novel mechanisms beyond JAK inhibitors Abnormal Blood Constitutional Cell Production3 Symptoms2,6,

  10. Slide 10: XPO1 Inhibition is a Multifaceted Approach to Inhibiting the Drivers of Myelofibrosis

    XPO1 Inhibition is a Multifaceted Approach to Inhibiting the Drivers of Myelofibrosis1-9 SEL ↓ Clonal cell division ↓ Splenomegaly XPO1 Inflammatory c-myc cytokine / chemokine ↓ Variant Allele Frequency c-myc (VAF) Oncogene XPO1 IκBα Oncogene mRNA ↓ NFκB activity ↓ Cytopenias, fibrosis, constitution

  11. Slide 11: Phase 3 SENTRY Trial of Selinexor with Ruxolitinib

    Phase 3 SENTRY Trial (XPORT-MF-034*) of Selinexor in Combination with Ruxolitinib in JAKi-Naïve Myelofibrosis Ruxolitiniba BID + Selinexor 60 mg QW Primary Endpoints JAKi-naïve Patients (tested sequentially) with Myelofibrosis (28-day cycle) R SVR35 week 24c (N=353) 2:1 + Ruxolitiniba BID + Abs-TSS

  12. Slide 12: 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) Difference in SVR35 at Week 24 (%) 21.82 Superior SVR35

  13. Slide 13: Rapid and Sustained Improvement in SVR35 Rates

    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

  14. Slide 14: Rapid, Deep and Sustained Spleen Reduction Observed

    Rapid, Deep and Sustained Spleen Reduction Observed with the Combination Relative to Ruxolitinib Alone 10 0 -10 -20 Mean(+/- SD) -30 -40 -50 -60 -70 Selinexor Selinexor++Ruxolitinib Ruxolitinib Placebo++Ruxolitinib Placebo Ruxolitinib -80 235 118 199 102 186 98 134 76 94 53 Baseline Week 12 Week 24

  15. Slide 15: Symptom Benefit at Week 24 was 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) Symptom Improvement Baseline n 235 117 Median 21.71 19.57 Mean 22.74 (11.877) 22.23 (13.031) Similar levels of absolut

  16. Slide 16: 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 + Overall Survival (OS) is a pre- Ruxolitinib (N = 235) Ruxolitinib (N = 118) specified secondary endpoin

  17. Slide 17: VAF Reduction in JAK2, CALR and MPL Driver Mutations

    Variant Allele Frequency (VAF) Reduction in JAK2, CALR and MPL Driver Mutations is Evidence of Potential Disease Modification1-3 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 c

  18. Slide 18: Manageable Safety and Tolerability Profile

    Manageable Safety and Tolerability Profile Selinexor + Placebo + Ruxolitinib Ruxolitinib (N = 234) (N = 116) Safety and tolerability is consistent All Grade TEAEs1 n (%) n (%) with the known profile of selinexor Thrombocytopenia 139 (59.4) 50 (43.1) and ruxolitinib individually Anaemia 134 (57.3) 67

  19. Slide 19: Encouraging Profile Observed with XPO1 Inhibition and Ruxolitinib

    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

  20. Slide 20: SENTRY Supports Selinexor's Potential Role in Myelofibrosis Therapy

    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 Global Regulatory Potential Role in Approved Class of Agencies on Data Myelofibrosis Therapy and Filing Plans Late-Breaking Oral P

  21. Slide 21: SENTRY-2 Phase 2 Trial Evaluating Selinexor Monotherapy

    SENTRY-2 (XPORT-MF-044*) Phase 2 Trial Evaluating Selinexor As Monotherapy in JAKi-Naïve MF Patients with Lower Platelet Counts Primary Endpoint Selinexor 60 mg QW • SVR35 at week 24 JAKi-naïve Patients with Myelofibrosis (n=29) Key Secondary Endpoints (n=58) Enrollment Completed • Abs-TSS at week 2

  22. Slide 22: Significant Opportunity to Expand into other MPNs

    Significant Opportunity to Expand into other MPNs Eltanexor is positioned Opportunity to expand to be our leading XPO1 inhibition across next generation other MPNs1 (PV & ET) XPO1 inhibitor in with eltanexor MPNs2 1. Myeloproliferative neoplasms (MPNs) include myelofibrosis (MF), polycythemia vera (

  23. Slide 23: Myelofibrosis Commercial Opportunity

    MYELOFIBROSIS COMMERCIAL OPPORTUNITY ©2026 KARYOPHARM THERAPEUTICS INC.

  24. Slide 24: No Novel Options Beyond JAKi

    Clear Opportunity to Redefine Standard of Care Beyond JAKi Therapies No Novel Ruxolitinib, ≤35% Options Current SoC, Patients on Beyond JAKi Approved 15 Ruxolitinib Therapies Years Ago Achieve SVR351 1. Ruxolitinib-alone arms of SIMPLIFY-1 Study, 2017; MANIFEST-2 Study, ASH 2023; and Transform-1 Stu

  25. Slide 25: Multi-Billion Dollar U.S. Market, Up To ~$1B Annually at Peak

    In a Multi-Billion Dollar U.S. Market, Selinexor plus Ruxolitinib Combination Could Deliver Up To ~$1B Annually1 in Net Sales at Peak Global Market Prevalence Newly Diagnosed Patients in the U.S. Annually INCIDENCE ✓ ~ 20,000 living with MF in the U.S.2 ✓ ~17,000 living with MF in the EU2 1L JAKi Na

  26. Slide 26: Established Commercial and Medical Affairs Leadership

    Established Commercial and Medical Affairs Leadership to Support Potential Launches Amama Sadiq MD, MPH SVP, Global Medical & Scientific Affairs Scientific & Medical Affairs Richard Paulson President and CEO Tim Suchanek SVP, National Sales Existing Sales Capabilities to Support Commercial Market Ac

  27. Slide 27: Targeted Launch with Commercial Organization Covering 100% of Key Accounts

    Positioning for Targeted Launch with Commercial Organization Covering 100% of Key Accounts Academic Community >70% of patients treated at Top 50 academic institutions1 Majority of patients U.S. treated in Myelofibrosis five large Community Majority of the 30% Patients Treated by Setting 70% Networks

  28. Slide 28: Opportunity to Rapidly Transform Frontline Myelofibrosis Treatment

    Opportunity to Rapidly Transform Frontline Myelofibrosis Treatment Landscape with Selinexor plus Ruxolitinib Significant Encouraging Convenient Concentrated Key unmet need with Efficacy Profile with oral once-weekly Account Base and two-thirds1 of patients rapid and sustained therapy combined strong

  29. Slide 29: Endometrial Cancer

    ENDOMETRIAL CANCER ©2026 KARYOPHARM THERAPEUTICS INC.

  30. Slide 30: Phase 3 XPORT-EC-042 Trial Focused on Patients with TP53wt EC

    Phase 3 XPORT-EC-042* Trial Focused on Patients with TP53wt EC that are either: i) pMMR, or ii) dMMR and Medically Ineligible to Receive a Checkpoint Inhibitor pMMR1 ~80% dMMR1 ~20% of overall EC population5-7 of overall EC population5-7 *NCT05611931 TP53wt > 50% Molecular characterization is the st

  31. Slide 31: No Personalized Biomarker-Driven Maintenance

    Opportunity to Define Maintenance Treatment Option for Patients with TP53 Wild-Type EC and Establish a New Standard of Care in TP53wt/pMMR No Personalized CPIs May Deliver Urgency to Less Benefit in the Biomarker-Driven Establish a TP53wt/pMMR1,2 Maintenance Subgroup with PFS TP53wt Directed Therapi

  32. Slide 32: SIENDO Showed HR of 0.41 and mPFS Benefit of 13.7 Months

    At Topline, SIENDO Showed a HR of 0.41 and a mPFS Benefit of 13.7 Months in TP53 Wild-Type Subgroup Compared to 3.7 Months for Patients on Placebo1 Selinexor: 13.7 months; Placebo: 3.7 months HR = 0.41 (95% CI 0.23-0.72) Two-sided nominal P value = 0.002 The safety and efficacy of selinexor in endom

  33. Slide 33: Longer-Term Follow Up from SIENDO Maintains HR of 0.44

    Longer-Term Follow Up from SIENDO Maintains Strong HR of 0.44 with Positively Evolving mPFS of 28.4 Months in TP53 Wild-Type Subgroup1 1.00 + Selinexor (n=77): 28.4 months (95% CI 13.1–NR) Placebo (n=36): 5.2 months (95% CI 2.0–13.1) HR: 0.44 (95% CI 0.27–0.73); One-sided nominal P-value = 0.0005 0.

  34. Slide 34: TP53 Wild-Type/pMMR Subgroup Longer-Term Follow Up

    TP53 Wild-Type/pMMR Subgroup; Longer-Term Follow Up from SIENDO Shows Greater Benefit with HR of 0.36 and mPFS of 39.5 Months1 1.00 Selinexor (n=47): 39.5 months (95% CI 19.3–NR) Placebo (n=23): 4.9 months (95% CI 2.0–NR)+ Selin e xor + Placebo HR: 0.36 (95% CI 0.19–0.71), One-sided nominal P-value

  35. Slide 35: Treatment Emergent Adverse Events from SIENDO TP53wt Subgroup

    Treatment Emergent Adverse Events from Longer-Term Follow-Up of the TP53wt Subgroup in the Phase 3 SIENDO Trial in Endometrial Cancer1 Selinexor (n=76*) Placebo (n=35*) Nausea 90% 13% 40% Vomiting 60% 3% 3% 14% Diarrhea 45% 4% 37% Constipation 33% 6% 40% Asthenia 36% 5% 26% Fatigue 36% 8% 20% Thromb

  36. Slide 36: XPORT-EC-042 Phase 3 Trial of Selinexor as Maintenance Therapy

    XPORT-EC-042* Phase 3, Randomized, Double-Blind Trial of Selinexor as Maintenance Therapy for Patients with TP53wt, Advanced or Recurrent EC Enrollment Completed: Study Conducted in Collaboration with ENGOT3 and GOG4 Final Enrollment Selinexor 60 mg orally QW Primary Endpoint5 (N=257)6 Until PD, tox

  37. Slide 37: Endometrial Cancer Commercial Opportunity

    ENDOMETRIAL CANCER COMMERCIAL OPPORTUNITY ©2026 KARYOPHARM THERAPEUTICS INC.

  38. Slide 38: First Novel Oral Maintenance Therapy in TP53 Wild-Type Endometrial Cancer

    Potential to be the First Novel Oral Maintenance Therapy in TP53 Wild-Type Endometrial Cancer in a Multi-Billion Dollar Marketplace Addressable Market Opportunity in the U.S. INCIDENCE Endometrial Cancer Marketplace1: 1L Advanced/Recurrent2 $2B+ pMMR2,3,4 dMMR2,3,4 ~17K ~80% ~20% TP53 WT > 50%3,4,5

  39. Slide 39: Opportunity to Transform Endometrial Cancer Maintenance Treatment

    Opportunity to Rapidly Transform Endometrial Cancer Maintenance Treatment Landscape for TP53 Wild-Type Patients with Selinexor Significant Superior Efficacy Convenient Concentrated Key unmet need in TP53 inTP53 wild type oral once-weekly Account Base and wild-type patients; patients with well therap

  40. Slide 40: Multiple Myeloma

    MULTIPLE MYELOMA ©2026 KARYOPHARM THERAPEUTICS INC.

  41. Slide 41: Primary Positioning in 2-4L Post-Anti-CD38 in the Community

    Our Primary Positioning in 2-4L Post-Anti-CD38 in the Community Supplemented with Expanding Use Pre- and Post T-cell Therapies Lines of Therapy 2L-4L 5L+ 1 Post Dara Unmet Need • Class switch option XVd and NCCN immediately after anti-CD38 Post-Anti-CD38 Therapy listings • Combinability (XPd, XKd, •

  42. Slide 42: Phase 3 Study XPORT-MM-031/EMN29 Evaluating SPd

    Phase 3 Global Study (XPORT-MM-031/ EMN291)* Evaluating SPd in Patients with Previously Treated Multiple Myeloma Enrollment Complete (n=117)2 SPd (n ~60) SEL: 40 mg3 QW PO D1, 8, 15 and 22 Patients with POM: 4 mg QD PO (D1-21) Pomalidomide-naïve DEX: 40 mg PO D1, 8, 15 and 22 RRMM 28-day cycle Prima

  43. Slide 43: Financial Highlights

    FINANCIAL HIGHLIGHTS ©2026 KARYOPHARM THERAPEUTICS INC.

  44. Slide 44: Driving Profitable Growth in Multiple Myeloma

    Driving Profitable Growth in Multiple Myeloma Q1 2026 Commercial Highlights Net Product Revenue • U.S. XPOVIO net product revenue was $29.2 million for Q1’26 compared to $21.1 million for Q1’25 driven by gross-to-net favorability $29.2M • Demand for XPOVIO was lower in Q1’26 $21.1M compared to Q1’25

  45. Slide 45: 1Q 2026 Financial Results and 2026 Guidance

    1Q 2026 Financial Results and 2026 Guidance 1Q 1Q Statements of Operations ($ millions) 2026 2025 2026 Financial Guidance1 Total Revenue $35.1 $30.0 • Total Revenue of $130-$150 million XPOVIO Net Product Revenue 29.2 21.1 License and Other Revenue 5.9 9.0 • U.S. XPOVIO Net Product Revenue of Total

  46. Slide 46: Appendix

    APPENDIX ©2026 KARYOPHARM THERAPEUTICS INC.

  47. Slide 47: Intellectual Property – Selinexor Protected by Global Patent Portfolio

    Intellectual Property – Selinexor Protected by Global Patent Portfolio Expiration of Last U.S. Expiration of Last U.S. Patent Covering Patent Covering Selinexor Polymorph Selinexor Composition used in Commercial of Matter Product July 2033 August 2035 Note: Selinexor's ex-U.S. patents will expire no

  48. Slide 48: Phase 2 XPORT-MF-035 Results in Myelofibrosis

    PHASE 2 XPORT-MF-035 RESULTS IN MYELOFIBROSIS ©2026 KARYOPHARM THERAPEUTICS INC.

  49. Slide 49: Data Suggest Single-Agent Activity & Disease Modification

    Data Suggest Single-Agent Activity & Disease Modification from Randomized Phase 2 Trial in Heavily Pre-Treated, Hard-to-Treat Myelofibrosis Phase 2 XPORT-MF-035 Selinexor vs. Physician's Choice (Primarily Ruxolitinib) in Previously Treated Myelofibrosis Single-Agent Clinical Lower Rates of All Activ

  50. Slide 50: XPORT-MF-035: Phase 2 Study of Selinexor Versus Physician's Choice

    XPORT-MF-0351: A Phase 2 Study of Single Agent Selinexor Versus Physician’s Choice in Patients with Previously Treated Myelofibrosis *Physician choice may include ruxolitinib retreatment, fedratinib, chemotherapy (e.g., hydroxyurea), Anagrelide, corticosteroid, hematopoietic growth factor, androgen,

  51. Slide 51: Demographics and Baseline Disease Characteristics Similar Across Arms

    Demographics and Baseline Disease Characteristics were Similar Across the Two Arms; Patient Population is a Heavily Pretreated, Hard to Treat Population Selinexor PC Total Selinexor PC Total Characteristic N=12 N=12 N=24 Characteristic N=12 N=12 N=24 Age, years, median (min, max) 70 (43, 78) 71 (60,

  52. Slide 52: Maximum Spleen Volume Reduction at Any Time

    Spleen Volume Reduction Rates More than Double with Selinexor Compared to Physician's Choice* in Efficacy Evaluable Population Physician's Choice (PC) Treated Selinexor Treated 50 Randomized to Selinexor Crossover to Selinexor 39.7 Reduction at Any Time (%) Maximum Spleen Volume 32.2 26.3 25 11.7 1.

  53. Slide 53: Patients Who Progressed on Physician's Choice and Received Selinexor

    Patients in XPORT-MF-035 Who Progressed on Physician's Choice (Rux) and Received Selinexor Showed a Meaningful Spleen Volume Reduction Spleen Volume 50 Reduction at Any Time (%) Maximum Spleen Volume 25 • All patients that crossed over to selinexor had a substantial spleen reduction 0 • 4/5 patients

  54. Slide 54: Robust Symptom Improvement with Selinexor Monotherapy

    Robust Symptom Improvement Assessed by TSS50 and Abs-TSS Observed with Selinexor Monotherapy in Efficacy Evaluable Population All Selinexor Treated PC (n=9) Selinexor (n=7) Patients*** (n=11) TSS50 at Week 24* 0 2 (28.6%) 2 (18.2%) Baseline TSS, Mean (SD) 17.28 (17.100) 18.80 (15.579) 17.64 (15.494)

  55. Slide 55: Hemoglobin Levels Meaningfully Higher with Selinexor

    Hemoglobin Levels Meaningfully Higher with Selinexor Compared to Physician's Choice Arm At data cutoff, mean HgB value was higher in the selinexor Phase 2 XPORT-MF-035 trial; data cut 2024.10.31 arm compared to physician’s choice (+ 1.7% vs −26.7%) The safety and efficacy of selinexor in myelofibros

  56. Slide 56: Selinexor Decreased Transfusion Burden by ~50%

    Selinexor Meaningfully Decreased Transfusion Burden by ~50% 1 Red Blood Cell Transfusions Received: 1 5/12 (SEL) vs 9/12 (PC) pts Avg Units Total Transfused Arm n Transfused Months Units Per 1 Month * Patient 0017-001 only got 1 dose but was later transfused with 9 units. This patient is excluded. P

  57. Slide 57: Key Cytokines Relevant to Myelofibrosis Pathogenesis

    Key Cytokines Relevant to Myelofibrosis Pathogenesis, Anemia and Symptom Development all Mediated Through NF-kB Malignant Mutated Clonal Expansion, • IL-6 MF Pathogenesis Hepatosplenomegaly and Bone Marrow • IL-8 Angiogenesis1,2 • IL-6 Constitutional Symptoms Drives Inflammation3,4 • IL-8 • TNF Sup

  58. Slide 58: Selinexor Induced Rapid Reduction in Cytokines

    Selinexor Induced Rapid and Substantial Reduction in Cytokines Relevant to MF Pathogenesis, Symptom Development and Anemia Key cytokines relevant to symptom development and MF pathogenesis. Cytokines reduced by selinexor but not PC • Increase Selinexor (5) • Decrease PC (Rux) (5) IL8 Cytokines assoc

  59. Slide 59: Manageable Safety Profile with No TEAEs Leading to Discontinuation

    Manageable Safety Profile with No TEAEs Leading to Treatment Discontinuation1 Treatment Emergent Adverse Events, any grade, (>/= 25% overall) Selinexor, n=12 PC, n=12 Decreased Weight 50% 50% Anemia 25% 58% Asthenia 42% 25% Nausea 33% 25% Thrombocytopenia 33% 25% Upper Respiratory Tract Infection 25

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