Karyopharm Therapeutics Inc. · NASDAQ:KPTI

Karyopharm Therapeutics — FY2024 Earnings Presentation

50 slides from Karyopharm Therapeutics's earnings presentation, Feb 19, 2025

  1. Slide 1: Fourth Quarter and Full Year 2024 Financial Results & Business Update

    Fourth Quarter and Full Year 2024 Financial Results & Business Update February 19, 2025

  2. Slide 2: On Today's Call

    On Today’s Call • Welcome Brendan Strong, SVP, Investor Relations and Corporate Communications • Overview Richard Paulson, President and Chief Executive Officer • Pipeline Update Dr. Reshma Rangwala, Chief Medical Officer and Head of Research • Commercial Highlights Sohanya Cheng, Chief Commercial O

  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 guidance on its 2025 total revenue, 2025 U

  4. Slide 4: Overview

    OVERVIEW Richard Paulson President and Chief Executive Officer 4 ©2025 KARYOPHARM THERAPEUTICS INC.

  5. Slide 5: Focused on Transformative Myelofibrosis Opportunity in 2025

    Focused on Transformative Myelofibrosis Opportunity in 2025 XPOVIO® (selinexor) Offers Growing Global Demand Myelofibrosis Peak Novel & Differentiated MoA for XPOVIO/NEXPOVIO® Annual Revenue that has Demonstrated (selinexor); Now Approved in Opportunity of Clinical Activity in Many Types of Cancer O

  6. Slide 6: Delivering for Myelofibrosis Patients

    Efficient Development Spanning Seven Years, Strongly Positioning Karyopharm for Potential Success in Myelofibrosis Executing Phase 3 SENTRY trial with quality and speed, faster than historical benchmarks Delivering for Learned from other MF programs; aligned with FDA Myelofibrosis on updated primary

  7. Slide 7: Believers in Selinexor's Potential to Improve Outcomes for Patients

    Leading KOLs Emphasize the Unmet Need in Myelofibrosis and are Strong Believers in Selinexor’s Potential to Improve Outcomes for Patients “ "There remains a tremendous unmet need in myelofibrosis, as less than half of patients achieve SVR35 with each of the approved JAK inhibitors and many patients

  8. Slide 8: Myelofibrosis Represents a Transformative Opportunity

    Myelofibrosis Represents a Transformative Opportunity, Building on our Foundation in Multiple Myeloma ~$1 billion (Myelofibrosis Peak U.S. Revenue Opportunity1,2,3) ✓ Top-line data expected from Phase 3 SENTRY trial in 2H’25 ✓ 75% of U.S. physicians surveyed indicated intent to ~$113 million adopt c

  9. Slide 9: Pipeline Update

    PIPELINE UPDATE Reshma Rangwala, MD, PhD Chief Medical Officer and Head of Research 9 ©2025 KARYOPHARM THERAPEUTICS INC.

  10. Slide 10: Focused High Potential Pipeline – Top Strategic Priority for 2025

    Focused High Potential Pipeline – Our Top Strategic Priority for 2025 is High-Quality Clinical Trial Execution on our Phase 3 SENTRY Trial in MF Indication Early Stage Mid Stage Late Stage Commercial Multiple myeloma (penta-refractory) w/dexamethasone Multiple myeloma (2L+) w/bortezomib + dexamethas

  11. Slide 11: Myelofibrosis

    MYELOFIBROSIS 11 ©2025 KARYOPHARM THERAPEUTICS INC.

  12. Slide 12: 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 Potential to Improve Outcomes by More Than Ruxolitinib Monotherapy Dou

  13. Slide 13: XPO1 Inhibition as a Fundamental Mechanism in Myelofibrosis

    XPO1 Inhibition is Potentially a Fundamental Mechanism in the Treatment of Myelofibrosis that Targets Both JAK-STAT and non-JAK-STAT Pathways1-10 Representing Opportunity for Additive or Synergistic Activity When Dosed in Combination with Ruxolitinib and Other JAK inhibitors, Plus Potential Use as M

  14. Slide 14: SIENDO TP53 Wild-Type Data Supports Mechanistic Rationale in MF

    Given that ~95% of Myelofibrosis is TP53 WT, Data from Phase 3 SIENDO Trial in Endometrial Cancer Supports Mechanistic Rationale in MF XPO1 Inhibition is Potentially a Fundamental Mechanism in the Progression Free Survival Data from the Post-Hoc TP53 Wild-Type Treatment of Myelofibrosis (WT) Subgrou

  15. Slide 15: Rapid and Deep SVR35 with Selinexor plus Ruxolitinib in Phase 1

    Rapid and Deep SVR35 Achieved with Selinexor 60 mg + Ruxolitinib in Phase 1 Trial* All Evaluable Patients2 Treated with Selinexor 60 mg SVR35 Achieved an SVR35 at Anytime 0 Selinexor 60 mg + ruxolitinib Maximum change in spleen volume from baseline (%) Population Timepoint n/N (%) -20 Week 12 10/121

  16. Slide 16: 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* TSS50, Total symptom improvement of ≥ 50% * Data cut August 1, 2023; Tantravahi S. et al. ASH 2023 Oral Presentation Publication. 1. SVR progression defined as less than or eq

  17. Slide 17: Absolute TSS as a 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 Robust endpoint supported by the FDA, investigators, and patient advocacy groups when comparing to active control arm Strong understanding of absolute change in sym

  18. Slide 18: Preliminary Improvement in Absolute TSS in Phase 1 Trial

    Selinexor + Ruxolitinib Has Shown Preliminary Evidence of Meaningful Improvement in Absolute TSS in Phase 1 Trial Absolute TSS (Abs-TSS) Phase 1 MANIFEST-2 TRANSFORM-1 Selinexor 60 mg + Ruxolitinib monotherapy Ruxolitinib monotherapy ruxolitinib1* arm2* arm3* Timepoint n=9 n=216 n=127 Average TSS at

  19. Slide 19: 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* Average Total Symptom Score Over Time1 The most common adverse events were GI side effects: • Nausea (79%, grade ≥3: 7%), anemia (64%, grade ≥3: 43%), thrombocytopenia (64%, grade ≥

  20. Slide 20: SENTRY Phase 3 Trial of Selinexor plus Ruxolitinib in JAKi Naïve MF

    SENTRY (XPORT-MF-034*) Phase 3 Trial of Selinexor in Combination with Ruxolitinib in JAKi Naïve Myelofibrosis Abs-TSS Replaced TSS50 as a Co-Primary Endpoint Study is Actively Enrolling Ruxolitinib1 BID + JAKi naïve Selinexor 60 mg QW Primary Endpoints* Patients with (28-day cycle) Myelofibrosis SVR

  21. Slide 21: Selinexor and Ruxolitinib May Establish a New Paradigm

    Combination of Selinexor and Ruxolitinib May Establish a New Paradigm by Substantially Improving Clinical Benefit for Myelofibrosis Patients* Deep Spleen Robust Symptom Durable Well Established Patient Volume Reduction Improvement Responses Safety Profile Convenience 79% achieved SVR35 Average 18.5

  22. Slide 22: Endometrial Cancer

    ENDOMETRIAL CANCER 22 ©2025 KARYOPHARM THERAPEUTICS INC.

  23. Slide 23: Key Updates to Phase 3 XPORT-EC-042 Trial in TP53 Wild-Type EC

    Key Updates to Phase 3 XPORT-EC-042 Trial in TP53 Wild-Type Endometrial Cancer ~220 patients Focused on TP53wt Targeted for enrollment in the modified intent-to-treat (mITT) mITT population will be primarily comprised population in order to maintain sufficient power for the of patients with tumors t

  24. Slide 24: TP53 is Central to XPO1 Inhibitors' Anticancer Activity

    TP53 is Central to XPO1 Inhibitors’ Anticancer Activity WITHOUT XPO1i Upstream effectors WITH XPO1i • Cell stressors • Oncogene activation XPO1 inhibition sequesters p53 in • DNA damage nuclei, leading to cell cycle arrest with impaired DNA repair and apoptosis1,5,7 Endometrial cancer (EC) cell line

  25. Slide 25: Focusing XPORT-EC-042 on TP53wt EC Patients

    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 pMMR1 ~80% dMMR1 ~20% overall EC pop4-6 overall EC pop4-6 TP53wt > 50% Molecular characterization is used to inform treatment decisions for patients with EC

  26. Slide 26: SIENDO Median PFS Benefit of 39.5 Months in TP53wt/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 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 n

  27. Slide 27: Treatment Emergent Adverse Events

    Treatment Emergent Adverse Events 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% Thrombocytopenia 42% 10% 3% Decreased appetite 36% 3% Neutropenia 34% 20% 6% Any grade in ≥20% patients Ane

  28. Slide 28: 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 TP53 Wild-Type Status is Assessed by Companion Diagnostic Partner Foundation Medicine2 Study is Actively Enrolling in Collaboration with ENGOT3 and GO

  29. Slide 29: Multiple Myeloma

    MULTIPLE MYELOMA 29 ©2025 KARYOPHARM THERAPEUTICS INC.

  30. Slide 30: Phase 3 Global Study XPORT-MM-031/EMN29 Evaluating SPd

    Phase 3 Global Study (XPORT-MM-031/ EMN292)* Evaluating SPd in Patients with Previously Treated Multiple Myeloma Enrollment Complete (n ~120)1 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 Prim

  31. Slide 31: Commercial Highlights

    COMMERCIAL HIGHLIGHTS Sohanya Cheng Chief Commercial Officer and Head of Business Development 31 ©2025 KARYOPHARM THERAPEUTICS INC.

  32. Slide 32: Total and Net Product Revenue in 2024

    Total and Net Product Revenue in 2024 2024 Highlights • XPOVIO net product revenue of $112.8 million and $29.3 million for FY 2024 and Q4 2024, respectively o Net product revenue impacted in 2024 by increased gross-to-net primarily driven by an $112.8M increase in 340B discounts and Medicare rebates

  33. Slide 33: Growing Global Demand for XPOVIO/NEXPOVIO

    Growing Global Demand for XPOVIO/NEXPOVIO® Selinexor Approved in over 45 Countries3 Reimbursement approvals in 2024 • United Kingdom1,2 • Italy1,2 • France2 • China2 • South Korea2 Regulatory approvals in 2024 • Turkey1,2 • Malaysia1,2 • Thailand1,2 • South Korea1 1. 2L+ MM. 2. ​Penta- or triple-cla

  34. Slide 34: Selinexor Potential for ~$1 Billion Annual U.S. Peak Revenue

    Selinexor has the Potential to Deliver ~$1 Billion in Annual U.S. Peak Revenue1 as the First Approved Combination Therapy in JAKi Naïve Myelofibrosis Global Market Prevalence Newly Diagnosed Patients in the U.S. Annually INCIDENCE ✓ ~ 20,000 living with MF in the U.S.2 1L JAKi Naive4 ~7K ✓ ~17,000 l

  35. Slide 35: Well-Positioned for Rapid Launch in Myelofibrosis

    Well-Positioned for a Rapid and Successful Launch as Potentially the First Approved Combination Therapy in Myelofibrosis1 Significant Need Compelling Target Synergistic Customer Experienced to Improve SoC Product Profile Base Cross-Functional Hematology Team Less than half of First to market combina

  36. Slide 36: Endometrial Cancer: Potential First Oral Maintenance Therapy in TP53wt EC

    Endometrial Cancer: Potential to be the First Novel Oral Maintenance Therapy in TP53 Wild-Type Endometrial Cancer Addressable Market Opportunity in the U.S. Key Commercial Success Factors INCIDENCE First novel, biomarker-specific oral 1L Advanced/Recurrent1 1 maintenance therapy7 pMMR1 ~80% dMMR1 ~2

  37. Slide 37: Financial Highlights

    FINANCIAL HIGHLIGHTS Lori Macomber, CPA Chief Financial Officer and Treasurer 37 ©2025 KARYOPHARM THERAPEUTICS INC.

  38. Slide 38: Financial Results and Guidance

    Financial Results and Guidance 4Q 4Q YTD YTD Statements of Operations ($ millions) 2024 2023 2024 2023 2025 Financial Guidance Total Revenue $30.5 $33.7 $145.2 $146.0 • Total Revenue of $140-$155 million XPOVIO Net Sales 29.3 25.1 112.8 112.0 License and Other Revenue 1.3 8.7 32.4 34.0 • U.S. XPOVIO

  39. Slide 39: Closing Remarks

    CLOSING REMARKS Richard Paulson President and Chief Executive Officer 39 ©2025 KARYOPHARM THERAPEUTICS INC.

  40. Slide 40: 2025 Objectives and Milestones

    2025 Objectives and Milestones Maintain the Company’s Profitable Commercial Report Top-Line Results from Foundation in the the Phase 3 SENTRY Trial Competitive Multiple Report Preliminary in 2H’25; Represents Potentially Myeloma Marketplace and Data from the Phase 2 Transformative Opportunity to Dri

  41. Slide 41: 2025 is a Transformative Year

    2025 is a Transformative Year – Delivering for Patients, Employees and Shareholders Focused on clinical Phase 3 SENTRY Positive data may trial execution and trial top-line enable transformative, completing enrollment data readout ~$1 billion peak U.S. of Phase 3 SENTRY expected in revenue opportunit

  42. Slide 42: Appendix

    APPENDIX ©2025 KARYOPHARM THERAPEUTICS INC.

  43. Slide 43: Optimizing Selinexor Dose to Improve Patient Experience

    Optimizing Selinexor Dose to Improve Patient Experience and Overall Benefit STORM BOSTON STOMP SIENDO XPORT- EC SENTRY EMN29 160 mg 100 mg 100-60mg 80 mg 60 mg 60 mg 40 mg (80 mg BIW) QW QW QW QW QW QW Multiple Multiple Multiple Endometrial Endometrial Multiple Myeloma Myeloma Myeloma Cancer Cancer

  44. Slide 44: SENTRY-2 Phase 2 Trial of Selinexor Monotherapy in JAKi Naïve MF

    SENTRY-2 (XPORT-MF-044*) Phase 2 Trial Evaluating Selinexor As Monotherapy in JAKi Naïve MF Patients with Lower Platelet Counts Primary Endpoint JAKi naïve Patients Selinexor 60 mg QW • SVR35 at week 24 with Myelofibrosis (n=29) Key Secondary Endpoints (n=58) Selinexor 40 mg QW • TSS50 at week 241 P

  45. Slide 45: Manageable Side Effect Profile with Selinexor/Ruxolitinib

    Manageable Side Effect Profile Observed with Selinexor/Ruxolitinib; Profile is Consistent with Other MF Therapies and Enables Long-term Treatment Selinexor 60 mg QW + Treatment Related Adverse Events (TEAEs) ruxolitinib (n = 14) Any grade (≥ 30% overall), n (%) Nausea 11 (78.6) • Treatment related d

  46. Slide 46: Improvement in All Symptom Domains in Phase 1 Trial

    Selinexor + Ruxolitinib Showed Improvement in all Symptom Domains1 in Ph1 Trial Mean % Change at Week 24 in Symptom Domains2 The safety and efficacy of selinexor in myelofibrosis has not been established and has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibr

  47. Slide 47: Total Symptom Score Evaluation - MFSAF v4 Questionnaire

    Total Symptom Score Evaluation - MFSAF v4 Questionnaire Domains Questions Scoring Scale 1. During the past 24 hours, how severe was your worst fatigue Fatigue (symptom absent) 0-10 (worst) (weariness, tiredness)? 2. During the past 24 hours, how severe was your worst night Night Sweats (symptom abse

  48. Slide 48: SIENDO Median PFS Benefit 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* 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 Pr

  49. Slide 49: SIENDO Median PFS Benefit 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* TP53wt/dMMR* subgroup 1.00 Selinexor (n=20): 13.1 months (95% CI 3.6–NR) Placebo (n=9): 3.7 months (95% CI 1.9–NR) + Selin e xor + Placebo HR: 0.49 (95% CI 0.18–1.34); One-sided nominal P-valu

  50. Slide 50: Preliminary Overall Survival Data from SIENDO Trial

    Preliminary Overall Survival Data from SIENDO Trial (ASCO 2024) Nominal one- Median No. w/ Median, months Overall matu HR (95% CI) sided P- follow up events (%) (95% CI) rity (%) value (months) TP53wt Selinexor (n=77) 24.7% NR (45.4–NR) 0.65 29.2% 0.11 36.8 Placebo (n=36) 38.9% NR (35.2–NR) (0.32–1.

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