Karyopharm Therapeutics Inc. · NASDAQ:KPTI
Karyopharm Therapeutics — Q2 2025 Earnings Presentation
34 slides from Karyopharm Therapeutics's earnings presentation, Aug 11, 2025
Slide 1: Second Quarter 2025 Financial Results & Business Update
Second Quarter 2025 Financial Results & Business Update August 11, 2025
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
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
Slide 4: Overview
OVERVIEW Richard Paulson President and Chief Executive Officer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 5: Focused on Transformative Myelofibrosis Opportunity
Focused on Transformative Myelofibrosis Opportunity Exploring financing transactions and strategic alternatives to extend cash runway and maximize value XPOVIO® (selinexor) Has a Growing Global Demand Myelofibrosis Peak Novel & Differentiated MoA for XPOVIO/NEXPOVIO® Annual Revenue that has the Pote
Slide 6: Delivering for Myelofibrosis Patients
Efficient Development Spanning Seven Years, Consistently Building a Strong Profile for Potential Success in Myelofibrosis Blinded safety data from Phase 3 may suggest improved safety profile based on extrapolated analysis; minimal TEAEs leading to discontinuation Delivering for Phase 2 in JAKi pre-t
Slide 7: Leading KOL Emphasizes the Unmet Need in Myelofibrosis
Leading KOL Emphasizes the Unmet Need in Myelofibrosis and is a Strong Believer in Selinexor’s Potential to Improve Outcomes for Patients “ “I’m excited about the SENTRY trial because it is trying to move the myelofibrosis field forward by introducing combinations of therapy early on that don’t have
Slide 8: Myelofibrosis Represents a Transformative Opportunity
Myelofibrosis Represents a Transformative Opportunity, Building on our Foundation in Multiple Myeloma Up to ~$1 billion (Myelofibrosis Peak U.S. Revenue Opportunity1,2,3) ✓ 2024 ruxolitinib myelofibrosis U.S. sales of $1.1 billion4 ✓ Complimentary to ruxolitinib, growing market from ~$113 million 30
Slide 9: Pipeline Update
PIPELINE UPDATE Reshma Rangwala, MD, PhD Chief Medical Officer and Head of Research ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 10: XPO1 Inhibition is Potentially 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
Slide 11: Selinexor plus Ruxolitinib May Establish a New Paradigm
Selinexor plus Ruxolitinib May Potentially Establish a New Paradigm by Substantially Improving Clinical Benefit for Myelofibrosis Patients* Four Key Pillars in Myelofibrosis Safety Spleen Symptom Hemoglobin Disease Improving Volume Improvement Stabilization4 Modification Safety Profile with Selinexo
Slide 12: SENTRY Phase 3 Trial of Selinexor with Ruxolitinib in JAKi Naïve MF
SENTRY (XPORT-MF-034*) Phase 3 Trial of Selinexor in Combination with Ruxolitinib in JAKi Naïve Myelofibrosis Ruxolitinib1 BID + Primary Endpoints JAKi naïve Selinexor 60 mg QW (tested sequentially) Patients with (28-day cycle) Myelofibrosis SVR35 week 243 (N ~350) R Abs-TSS + 2:1 week 242,3 Plt >10
Slide 13: Preliminary Extrapolated Grade 3+ TEAEs from Blinded SENTRY Safety Data
Preliminary Extrapolated Grade 3+ TEAEs from Blinded Safety Data from Phase 3 SENTRY Trial Point to Potential for Selinexor plus Ruxolitinib to have a More Favorable Safety Profile than Rux Alone1 Summary of Treatment Emergent Adverse Events (TEAEs) from Phase 3 SENTRY Trial Ruxolitinib Selinexor +
Slide 14: Potential for Lower Rates of Grade 3+ Anemia
Encouraged by the Potential for Lower Rates of Grade 3+ Anemia Based on Preliminary Extrapolated Safety Data on Selinexor plus Ruxolitinib from Blinded Safety Data1 Preliminary Blinded Safety Data from Phase 3 SENTRY (2:1 randomization), n= 61 Ruxolitinib Historical Adverse Selinexor + Ruxolitinib T
Slide 15: Evidence of Bone Marrow Modification from Phase 1 Portion of SENTRY
Encouraging Evidence of Bone Marrow Modification from Patient Treated with Selinexor plus Ruxolitinib from Phase 1 Portion of SENTRY Trial Treatment with suboptimal doses of ruxolitinib suggests the potentially fundamental role selinexor may have in myelofibrosis Pre-treatment Week 24 • Enrolled on
Slide 16: Endometrial Cancer
ENDOMETRIAL CANCER ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 17: Focusing Phase 3 XPORT-EC-042 Trial 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
Slide 18: XPORT-EC-042 Phase 3 Trial of Selinexor as Maintenance Therapy
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
Slide 19: Multiple Myeloma
MULTIPLE MYELOMA ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 20: Phase 3 XPORT-MM-031 Study Evaluating SPd in Previously Treated Multiple Myeloma
Phase 3 Global Study (XPORT-MM-031/ EMN291)* Evaluating SPd in Patients with Previously Treated Multiple Myeloma Enrollment Complete (n ~120)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 Prim
Slide 21: Commercial Highlights
COMMERCIAL HIGHLIGHTS Sohanya Cheng Chief Commercial Officer and Head of Business Development ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 22: Commercial Highlights: Q2 2025 Highlights
Commercial Highlights Q2 2025 Highlights Net Product Revenue Grew 6% YoY • U.S. net product revenue was $29.7 million in 2Q’25, up 6% from $28.0 million in 2Q’24. • Demand for XPOVIO was consistent in 2Q’25 compared $29.7M to 2Q’24, with the community setting continuing to drive approximately 60% of
Slide 23: Selinexor Potential for Up to ~$1 Billion Annual U.S. Peak Revenue
Selinexor has the Potential to Deliver Up to ~$1 Billion in Annual U.S. Peak Revenue1 as the First Approved Combination Therapy in JAKi Naïve Myelofibrosis Global Market Prevalence Newly Diagnosed Patients in the U.S. Annually INCIDENCE ✓ ~ 20,000 living with MF in the U.S.2 1L JAKi Naive4 ~7K ✓ ~17
Slide 24: Well-Positioned for a Rapid and Successful Launch in Myelofibrosis
Well-Positioned for a Rapid and Successful Launch as Potentially the First Approved Combination Therapy in Myelofibrosis1 Significant Need Compelling Target Synergistic Customer Experienced to Improve SoC Product Profile Base Cross-Functional Hematology Team Less than half of First to market combina
Slide 25: Endometrial Cancer: Potential First Novel Oral Maintenance Therapy
Endometrial Cancer: Potential to be the First Novel Oral Maintenance Therapy in TP53 Wild-Type Endometrial Cancer Addressable Market Opportunity in the U.S. Key Commercial Success Factors INCIDENCE First novel, biomarker-specific oral 1L Advanced/Recurrent1 1 maintenance therapy7 pMMR1 ~80% dMMR1 ~2
Slide 26: Financial Highlights
FINANCIAL HIGHLIGHTS Lori Macomber, CPA Chief Financial Officer and Treasurer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 27: Q2 2025 Financial Results and Guidance
Q2 2025 Financial Results and Guidance 2Q 2Q Statements of Operations ($ millions) 2025 2024 2025 Financial Guidance Total Revenue $37.9 $42.8 • Total Revenue of $140-$155 million XPOVIO Net Product Revenue 29.7 28.0 License and Other Revenue 8.2 14.8 • U.S. XPOVIO Net Product Revenue of $110-$120 m
Slide 28: Closing Remarks
CLOSING REMARKS Richard Paulson President and Chief Executive Officer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 29: Exploring Financing Transactions and Strategic Alternatives
Exploring Financing Transactions and Strategic Alternatives to Extend Cash Runway, Maximize Value and Deliver on Potentially Transformative Opportunities Report Top-Line Results Report Top-Line Results from from the Phase 3 XPORT- Maintain the Company’s the Phase 3 SENTRY Trial EC-042 Trial in mid-2
Slide 30: Appendix
APPENDIX ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 31: 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 Indication Early Stage Mid Stage Late Stage Commercial Multiple myeloma (penta-refractory) w/dexamethasone Multiple myeloma (2L+) w/bortezomib + dexamethas
Slide 32: 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
Slide 33: 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
Slide 34: 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
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