Karyopharm Therapeutics Inc. · NASDAQ:KPTI

Karyopharm Therapeutics — Investor Presentation (July 2025)

53 slides from Karyopharm Therapeutics's investor presentation, Jul 11, 2025

  1. Slide 1: Confidential Investor Presentation July 2025

    Confidential Investor Presentation July 2025 ©2025 KARYOPHARM THERAPEUTICS INC. | CONFIDENTIAL & PROPRIETARY

  2. Slide 2: Forward-Looking Statements and Disclaimers

    Forward-Looking Statements and Disclaimers 2 This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements with respect to the possible achievement of Karyopharm’s discovery and

  3. Slide 3: Focused on Transformative Myelofibrosis Opportunity in 2025

    Focused on Transformative Myelofibrosis Opportunity in 2025 3 1. Makker ASCO 2024; Tantravahi ASH 2023; Mechanism of Action (MoA). 2. Includes projected potential selinexor revenues in JAKi-naïve myelofibrosis. 3. Annual U.S. peak revenue opportunity is not guidance, but instead represents what the

  4. Slide 4: Passed Futility Analysis; Expect to Complete Enrollment of Phase 3 SENTRY Trial in August

    Passed Futility Analysis Expect to Complete Enrollment of Phase 3 SENTRY Trial in August Data Suggest Single-Agent Activity & Disease Modification from Phase 2 in Previously Treated Myelofibrosis 1Q’25 Financial Results Interim Blinded Safety Data from Phase 3 SENTRY Trial (n=61) Extrapolations: Pot

  5. Slide 5: Myelofibrosis Represents a Transformative Opportunity, Building on our Foundation in Multiple Myeloma

    Myelofibrosis Represents a Transformative Opportunity, Building on our Foundation in Multiple Myeloma 5 ~$113 million (XPOVIO Net Product Revenue in 2024) Profitable commercial organization executing well in the highly competitive multiple myeloma marketplace Working to drive continued revenue growt

  6. Slide 6: Efficient Development Spanning Seven Years in Myelofibrosis

    Efficient Development Spanning Seven Years, Consistently Building a Strong Profile for Potential Success in Myelofibrosis Demonstrated monotherapy activity signal (ESSENTIAL IST at ASH 2021) Learned from other MF programs; aligned with FDA on updated primary endpoints, increasing PoS Blinded safety

  7. Slide 7: Opportunity to Substantially Improve Patient Outcomes Across All Four Key Pillars in JAKi Naive Myelofibrosis

    Opportunity to Substantially Improve Patient Outcomes Across All Four Key Pillars in JAKi Naïve Myelofibrosis Spleen Volume Reduction Only ~35% of patients achieve SVR35 today1 Inconsistent benefit across key subgroups Symptom Improvement Average 11–14 point improvement relative to baseline2,3 <50%

  8. Slide 8: Selinexor plus Ruxolitinib May Potentially Establish a New Paradigm

    Selinexor plus Ruxolitinib May Potentially Establish a New Paradigm by Substantially Improving Clinical Benefit for Myelofibrosis Patients* 8 Spleen Volume Reduction 79% achieved SVR35 (ITT) at week 241 Over 2X the responders compared to ruxolitinib historical spleen response at week 242 100% effica

  9. Slide 9: New Selinexor Monotherapy Data Strengthens Confidence in Combination Opportunity

    New Selinexor Monotherapy Data Strengthens Confidence in Combination Opportunity Given the Potential Synergy with Selinexor + Ruxolitinib Based on Phase 2 open-label, XPORT-MF-035 trial (n=24) and extrapolated blinded safety data from Phase 3 SENTRY trial. 2. XPOVIO USPI The safety and efficacy of s

  10. Slide 10: XPORT-MF-035: Phase 2 Study of Single Agent Selinexor Versus Physician's Choice

    XPORT-MF-0351: A Phase 2 Study 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, in

  11. Slide 11: Demographics and Baseline Disease Characteristics Similar Across the Two Arms

    Demographics and Baseline Disease Characteristics were Similar Across the Two Arms; Patient Population is a Heavily Pretreated, Hard to Treat Population Characteristic Selinexor N=12 PC N=12 Total N=24 Age, years, median (min, max) 70 (43, 78) 71 (60, 79) 70 (43, 79) Age category 18 -50 1 (8) 0 1 (4

  12. Slide 12: Spleen Volume Reduction Rates More than Double with Selinexor

    Spleen Volume Reduction Rates More than Double with Selinexor Compared to Physicians Choice* in Efficacy Evaluable Population 12 PC n(%)** Selinexor n(%)** SVR25 3/8 (38%) 8/12 (67%) SVR35 1/8 (13%) 4/12 (33%) SVR35, spleen volume reduction ≥35%; SVR25, spleen volume reduction >25% Maximum Spleen Vo

  13. Slide 13: Patients Who Progressed on Physician's Choice and Received Selinexor Showed Meaningful Spleen Volume Reduction

    Patients in XPORT-MF-035 Who Progressed on Physician's Choice (Rux) and Received Selinexor Showed a Meaningful Spleen Volume Reduction 13 -25 -35 0 25 50 On PC (Max SVR Reduction) On PC at progression or inadequate response On SEL after crossover (Max SVR Reduction) Maximum Spleen Volume Reduction a

  14. Slide 14: Robust Symptom Improvement Assessed by TSS50 and Abs-TSS with Selinexor Monotherapy

    Robust Symptom Improvement Assessed by TSS50 and Abs-TSS Observed with Selinexor Monotherapy in Efficacy Evaluable Population Data cut 2024.10.31 *TSS evaluable population: >0 TSS at baseline and any non-missing TSS evaluations post-baseline; patients with missing data at week 24 were considered non

  15. Slide 15: Hemoglobin Levels Meaningfully Higher with Selinexor Compared to Physician's Choice

    Hemoglobin Levels Meaningfully Higher with Selinexor Compared to Physician’s Choice Data cut 2024.10.31 At data cutoff, mean HgB value was higher in the selinexor arm compared to physician’s choice (+ 1.7% vs −26.7%) 15 Arm

  16. Slide 16: Selinexor Meaningfully Decreased Transfusion Burden by ~50%

    Selinexor Meaningfully Decreased Transfusion Burden by ~50% 16 Data cut 2024.10.31 * Patient 0017-001 only got 1 dose but was later transfused with 9 units. This patient is excluded. Red Blood Cell Transfusions Received: 5/12 (SEL) vs 9/12 (PC) pts Arm Units Transfused Total Months Avg Transfused Un

  17. Slide 17: Key Cytokines Relevant to Myelofibrosis Pathogenesis, Anemia and Symptom Development Mediated Through NF-kB

    Key Cytokines Relevant to Myelofibrosis Pathogenesis, Anemia and Symptom Development all Mediated Through NF-kB 1. Li et al J Immunol 2003. 2. Subotički T Int J Mol Sci. 2021.. 3. Hasselbalch Cytokine Growth Factor Rev 2013 4. Geyer et al Mediators of Inflammation 2015 . 5. Madeddu Front. Physiol. 2

  18. Slide 18: Selinexor Induced Rapid and Substantial Reduction in Cytokines Relevant to MF

    Selinexor Induced Rapid and Substantial Reduction in Cytokines Relevant to MF Pathogenesis, Symptom Development and Anemia 18 PC (Rux) (5) Cytokines reduced by selinexor but not PC Selinexor (5) Increase Decrease IL8 Key cytokines relevant to symptom development and MF pathogenesis. Dendrogram showi

  19. Slide 19: Manageable Safety Profile with No TEAEs Leading to Treatment 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

  20. Slide 20: SENTRY Phase 3 Trial of Selinexor with Ruxolitinib; Passed Futility Analysis

    SENTRY (XPORT-MF-034*) Phase 3 Trial of Selinexor in Combination with Ruxolitinib in JAKi Naïve Myelofibrosis; SENTRY Passed Futility Analysis; Study Continues as Planned 20 1. Ruxolitinib dose based on platelet count per prescribing information. 2. Evaluated by myelofibrosis assessment form (MFSAF

  21. Slide 21: Potential for Lower Gr 3+ Anemia and Treatment Discontinuations Based on Blinded SENTRY Safety Data

    Potential for Lower Gr 3+ Anemia and Treatment Discontinuations due to TEAEs Based Upon Extrapolated Data with Seli+Rux Compared to Historical Ruxolitinib Based upon Blinded Safety Data from Phase 3 SENTRY1 Treatment Emergent Adverse Events (TEAEs) Total (N=61) n(%) Patients with At Least One TEAE 5

  22. Slide 22: Selinexor Potential to Deliver Up to ~$1 Billion in Annual U.S. Peak Revenue

    Selinexor has the Potential to Deliver Up to ~$1 Billion in Annual U.S. Peak Revenue1 as the First Approved Combination Therapy in JAKi Naïve Myelofibrosis 22 1. Annual U.S. peak revenue opportunity is not guidance, but instead represents what the Company believes to be Karyopharm’s peak revenue opp

  23. Slide 23: Financial Update

    BELIEVERS IN THE EXTRAORDINARY FINANCIAL UPDATE &karyopharm ©2025 KARYOPHARM THERAPEUTICS INC. | CONFIDENTIAL & PROPRIETARY

  24. Slide 24: Q1 2025 Highlights

    Q1 2025 Highlights XPOVIO gross revenue was $38.3 million and net product revenue was $21.1 million for Q1 2025 Net product revenue adversely impacted by $5.0 million increase in the product return reserve due to atypical returns of expired product, primarily 80 mg and 100 mg XPOVIO units Demand gre

  25. Slide 25: Q1 2025 Financial Results

    Q1 2025 Financial Results Statements of Operations ($ millions) 1Q 2025 1Q 2024 Total Revenue $30.0 $33.1 XPOVIO Net Product Revenue 21.1 26.0 License and Other Revenue 9.0 7.1 Total Operating Expenses $63.3 $66.9 Cost of Sales 1.3 1.9 Research and Development Expenses 34.6 35.4 Selling, General & A

  26. Slide 26: Appendix

    APPENDIX ©2025 KARYOPHARM THERAPEUTICS INC. | CONFIDENTIAL & PROPRIETARY

  27. Slide 27: Focused High Potential Pipeline

    Focused High Potential Pipeline – Our Top Strategic Priority for 2025 is High-Quality Clinical Trial Execution on our Phase 3 SENTRY Trial in MF 27 1. EMN29 Study: Sponsored by European Myeloma Network. 2. XPORT-DLBCL-030 is a Phase 2/3. 3. Further development of the Company’s early-stage pipeline i

  28. Slide 28: Intellectual Property – Selinexor Protected by Global Patent Portfolio

    Intellectual Property – Selinexor Protected by Global Patent Portfolio 28 August 2035 July 2033 Note: Selinexor's ex-U.S. patents will expire no earlier than 2032 Expiration of Last U.S. Patent Covering Selinexor Composition of Matter Expiration of Last U.S. Patent Covering Selinexor Polymorph used

  29. Slide 29: Myelofibrosis

    BELIEVERS IN THE EXTRAORDINARY MYELOFIBROSIS &)Karyopharm ©2025 KARYOPHARM THERAPEUTICS INC. | CONFIDENTIAL & PROPRIETARY

  30. Slide 30: Selinexor Opportunity to Be First Approved Combination Therapy in Myelofibrosis

    Selinexor has the Opportunity to be the First Approved Combination Therapy to Transform Current Standard of Care (SoC) in Myelofibrosis Unmet Need in JAKi Naïve MF Selinexor as Potential New SoC Limited Outcomes for Patients with Ruxolitinib Monotherapy Only ~35% of patients achieve SVR351,2 and <50

  31. Slide 31: ~95% of Myelofibrosis is TP53 WT; SIENDO Data Supports Mechanistic Rationale

    Given that ~95% of Myelofibrosis is TP53 WT, Data from Phase 3 SIENDO Trial in Endometrial Cancer Supports Mechanistic Rationale in Myelofibrosis Data cutoff date: April 1, 2024 HR, hazard ratio; NR, not reached. * Molecular status determined by sequencing (TP53wt, n=99; TP53 mutant, n=97) and if NG

  32. Slide 32: Rapid and Deep SVR35 Achieved with Selinexor + Ruxolitinib in Phase 1

    Rapid and Deep SVR35 Achieved with Selinexor 60 mg + Ruxolitinib in Phase 1 Trial* SVR35 Population Timepoint Selinexor 60 mg + ruxolitinib n/N (%) Efficacy Evaluable Week 12 10/121 (83.3) Week 24 11/12 (91.7) Intent-to-Treat Week 12 10/14 (71.4) Week 24 11/14 (78.6) All Evaluable Patients2 Treated

  33. Slide 33: Sustained Responses for SVR35 or TSS50 Responders in Phase 1

    Sustained Responses with No Progressions for SVR35 or TSS50 Responders1,2 on Selinexor 60 mg + Ruxolitinib in Phase 1 Trial* * Data cut August 1, 2023; Tantravahi S. et al. ASH 2023 Oral Presentation Publication. 1. SVR progression defined as less than or equal to 35% spleen volume reduction from ba

  34. Slide 34: Absolute TSS as Co-primary Endpoint Increases Confidence in SENTRY

    Incorporating Absolute TSS* as a Co-primary Endpoint, a Comprehensive Assessment of Symptom Improvement, Increases Confidence in SENTRY 1. Results from Phase 1 portion of SENTRY trial evaluating selinexor+ ruxolitinib in JAKi naïve patents; data cut August 1, 2023. 2. Average reduction in total symp

  35. Slide 35: Selinexor + Ruxolitinib Preliminary Improvement in Absolute TSS in Phase 1

    Selinexor + Ruxolitinib Has Shown Preliminary Evidence of Meaningful Improvement in Absolute TSS in Phase 1 Trial * Abs-TSS score from Phase 1 portion of SENTRY excluded fatigue, MANIFEST-2 and TRANSFORM-1 included fatigue. 1. Results from Phase 1 portion of SENTRY trial evaluating selinexor + ruxol

  36. Slide 36: Rapid, Deep and Sustained Improvement in Average Total Symptom Score

    Selinexor + Ruxolitinib Shows a Rapid, Deep and Sustained Improvement in Average Total Symptom Score in Phase 1 Trial* * Data cut August 1, 2023; Tantravahi S. et al. ASH 2023 Oral Presentation Publication. 1. Average reduction in total symptom score at week 24 relative to baseline, calculated for e

  37. Slide 37: Well-Positioned for Rapid and Successful Launch in Myelofibrosis

    Well-Positioned for a Rapid and Successful Launch as Potentially the First Approved Combination Therapy in Myelofibrosis1 1. Pending positive data from the Phase 3 SENTRY trial and regulatory approval. 2. MANIFEST and TRANSFORM Phase 3 studies. 3. Data on file qualitative market research May 2023, N

  38. Slide 38: Improvement in all Symptom Domains in Phase 1 Trial

    Selinexor + Ruxolitinib Showed Improvement in all Symptom Domains1 in Phase 1 Trial Data cut August 1, 2023 1. Excluding fatigue 2. Percentage change from baseline to Week 24 was calculated for each symptom domain for subjects (N) who have non-zero and non-missing baseline score and non-missing Week

  39. Slide 39: Symptom Assessment Form Domains and Questions

    Domains Questions Scoring Scale Fatigue 1. During the past 24 hours, how severe was your worst fatigue (weariness, tiredness)? (symptom absent) 0-10 (worst) Night Sweats 2. During the past 24 hours, how severe was your worst night sweats (or feeling hot of flushed)? (symptom absent) 0-10 (worst) Itc

  40. Slide 40: Endometrial Cancer

    BELIEVERS IN THE EXTRAORDINARY ENDOMETRIAL CANCER ©2025 KARYOPHARM THERAPEUTICS INC. | CONFIDENTIAL & PROPRIETARY.

  41. Slide 41: Potential Paradigm Shift for TP53 Wild-Type Endometrial Cancer

    XPO1 inhibition forces retention of p53 in the cell nucleus, allowing it to carry out its tumor suppressor and other regulatory functions Generated strong hypothesis in patients with TP53 WT EC Potential to improve treatment options for pMMR1 (proficient mismatch repair), which represents ~80% of ad

  42. Slide 42: TP53 is Central to XPO1 Inhibitors' Anticancer Activity

    WITHOUT XPO1i WITH XPO1i TP53 is Central to XPO1 Inhibitors’ Anticancer Activity Cell stressors Oncogene activation DNA damage XPO1 inhibition sequesters p53 in nuclei, leading to cell cycle arrest with impaired DNA repair and apoptosis1,5,7 XPO1i may have anticancer activity across multiple TP53wt

  43. Slide 43: Focusing XPORT-EC-042 Trial on Patients with TP53wt EC

    Focusing Phase 3 XPORT-EC-042 Trial on Patients with TP53wt EC that are pMMR or dMMR and Medically Ineligible to Receive a Checkpoint Inhibitor EC, endometrial cancer; ITT, intent-to-treat; dMMR, deficient mismatch repair; pMMR, proficient mismatch repair; PFS, progression-free survival; TP53, tumor

  44. Slide 44: SIENDO Phase 3 Randomized Double-Blind Trial of Selinexor Maintenance Therapy

    Stratification Primary stage IV vs recurrent PR vs CR Total patients enrolled (N = 263) Female adults with stage IV or first relapsed EC Received ≥ 12 weeks of platinum-based chemotherapy Prior surgery, radiotherapy or hormonal therapy allowed Enrollment: January 2018-December 2021 SIENDO*: Phase 3,

  45. Slide 45: Potential to Shift 1L Treatment Paradigm in TP53wt Population

    Potential to Shift 1L Tx Paradigm in Overall TP53wt Population, with Unparalleled mPFS Data at ~40 Months and HR 0.36 in TP53wt/pMMR TP53 Wild Type >50% Overall Population TP53 Mutant <50% Overall Population dMMR/MSI-H ~20% pMMR/MSS ~80% SELINEXOR *Selinexor is maintenance Tx only & does not include

  46. Slide 46: SIENDO: Median PFS of 28.4 Months in TP53 Wild-Type Subgroup

    Data from SIENDO Trial (ASCO 2024) Shows Encouraging Signal of Long-term Median PFS Benefit of 28.4 Months in TP53 Wild-Type Subgroup* Data cutoff date: April 1, 2024 HR, hazard ratio; NR, not reached. * Molecular status determined by sequencing (TP53 WT, n=99; TP53 mutant, n=97) and if NGS not avai

  47. Slide 47: SIENDO: Median PFS of 39.5 Months in TP53 Wild-Type/pMMR Subgroup

    Data from SIENDO Trial (ASCO 2024) Shows Encouraging Signal of Long-term Median PFS Benefit of 39.5 Months in TP53 Wild-Type/pMMR Subgroup1,2 Data cutoff date: April 1, 2024 1. Data presented at ASCO 2024 Annual Meeting. 2. Molecular status determined by sequencing (TP53 WT, n=99; TP53 mutant, n=97;

  48. Slide 48: SIENDO: Median PFS of 13.1 Months in TP53 Wild-Type/dMMR Subgroup

    Data from SIENDO Trial (ASCO 2024) Shows Median PFS Benefit of 13.1 Months in TP53 Wild-Type/dMMR Subgroup* Data cutoff date: April 1, 2024 HR, hazard ratio; NR, not reached. *Molecular status determined by sequencing (TP53wt, n=99; TP53 mutant, n=97; pMMR, n=164) and if NGS not available, by immuno

  49. Slide 49: Treatment Emergent Adverse Events

    Treatment Emergent Adverse Events Data cutoff date: April 1, 2024; Presented at ASCO 2024 Annual Meeting TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event. *Two patients total did not receive treatment (n=1, selinexor; n=1, placebo) and were excluded from this analysis. †

  50. Slide 50: Phase 3 XPORT-EC-042 Trial in TP53 Wild-Type Endometrial Cancer

    Phase 3 XPORT-EC-042 Trial in TP53 Wild-Type Endometrial Cancer ~276 patients Targeted for enrollment in the intent-to-treat (ITT) population Mid-’26 Expected timing for top-line data ~220 patients Targeted for enrollment in the modified intent-to-treat (mITT) population in order to maintain suffici

  51. Slide 51: Updated XPORT-EC-042 Phase 3 Trial Design

    Updated XPORT-EC-042* Phase 3, Randomized, Double-Blind Trial of Selinexor as Maintenance Therapy for Patients with TP53wt, Advanced or Recurrent EC1 Top-line data anticipated in mid-2026 TP53 Wild-Type Status is Assessed by Companion Diagnostic Partner Foundation Medicine2 Planned Enrollment (n ~27

  52. Slide 52: Endometrial Cancer: Potential 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 Anticipated rapid launch, if approved, with experienced commercialization capabilities including field, market access and MSLs First novel, biomarker-specific oral maintenance therapy7 ~

  53. Slide 53: Chemo-Alone Stabilized at ~40% Market Share for 1L pMMR

    Chemo-Alone has Stabilized at ~40% Market Share for 1L pMMR, Maintaining Opportunity for Selinexor Source: Brandimpact October’24 1L pMMR Market Shares (R3M) 1L dMMR Market Shares (R3M) 53

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