Karyopharm Therapeutics Inc. · NASDAQ:KPTI
Karyopharm Therapeutics — Q3 2025 Earnings Presentation
31 slides from Karyopharm Therapeutics's earnings presentation, Nov 3, 2025
Slide 1: Third Quarter 2025 Financial Results & Business Update
Third Quarter 2025 Financial Results & Business Update November 3, 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 • Phase 3 SENTRY Trial and Myelofibrosis Review Dr. Reshma Rangwala, Chief Medical Officer and Head of Research • Commercial Highlights and
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: Positioned to Execute on Potentially Transformative Opportunities
Positioned to Execute on Potentially Transformative Opportunities XPORT-EC-042 Commercial SENTRY Enrolled Financing Secured On-Track Execution Top-Line Data from Top-Line Data from Delivering Strong Cash Runway Phase 3 SENTRY Phase 3 Trial in Commercial Extended Trial in Endometrial Performance in i
Slide 6: Myelofibrosis Update
MYELOFIBROSIS UPDATE Reshma Rangwala, MD, PhD Chief Medical Officer and Head of Research ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 7: Myelofibrosis Is a Rare Blood Cancer Defined by Four Hallmarks
Myelofibrosis Is a Rare Blood Cancer Defined by Four Hallmarks1,2 Four Hallmarks of Myelofibrosis Median survival of patients with intermediate-to-high risk Enlarged myelofibrosis is 4 to 5 years4,9 Spleen5 The standard of care is Abnormal Blood Constitutional ruxolitinib which is Cell Production3 S
Slide 8: Selinexor's Complementary Datasets Strengthen Confidence in Myelofibrosis
Selinexor’s Complementary Datasets Strengthen Confidence in Myelofibrosis through Multi-Dimensional Apoptotic and Anti-Leukemic Effects Simultaneous 7+ Years of Data in Myelofibrosis targeting of relevant mechanisms Anti-inflammatory, Preclinical/ Clinical apoptotic and Selinexor Monotherapy and ant
Slide 9: XPO1 Inhibition is a Multifaceted Approach to Inhibiting the Drivers of Myelofibrosis
XPO1 Inhibition is a Multifaceted Approach to Inhibiting the Drivers of Myelofibrosis1-10 SEL ↓ Clonal cell division Splenomegaly XPO-1 Inflammatory c-myc cytokine / chemokine c-myc Oncogene XPO-1 IκBα Oncogene mRNA ↓ NFκB activity Cytopenias, fibrosis, constitutional symptoms SEL Tumor suppressor p
Slide 10: 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 Patients1 Spleen Volume Reduction Symptom Improvement Anemia Adverse Event rates 79% achieved Average 18.5 point SVR352,3 improvement in Lower rates of absolute-TSS relat
Slide 11: SENTRY Phase 3 Trial of Selinexor in Combination with Ruxolitinib in JAKi Naïve Myelofibrosis
SENTRY (XPORT-MF-034*) Phase 3 Trial of Selinexor in Combination with Ruxolitinib in JAKi Naïve Myelofibrosis Enrollment Completed September 2025 Ruxolitinib1 BID + JAKi naïve Primary Endpoints Selinexor 60 mg QW Patients with (tested sequentially) (28-day cycle) Myelofibrosis R SVR35 week 243 (N=35
Slide 12: Potential for Lower Rates of Grade 3+ Anemia Based on Preliminary Safety Data
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 Ruxolitinib Historical Selinexor + Ruxolitinib Phase 3 SENTRY (2:1 randomization), n= 61 Adverse E
Slide 13: Phase 1 Patient Case Shows Spleen and Symptom Improvement, Durability, and Disease Modification
Phase 1 SENTRY-034: Patient Case Shows Meaningful Spleen and Symptom Improvement, Durability, and Disease Modification Spleen Volume (cm3) TSS 2500 30 81 Year-old Female, Presenting with Secondary MF 2000 • Post-PV MF diagnosed in January 2022 SRV 35 Spleen Volume (cm3) 20 ◦ DIPSS+: Intermediate-2 1
Slide 14: Commercial Highlights
COMMERCIAL HIGHLIGHTS Sohanya Cheng Chief Commercial Officer and Head of Business Development ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 15: Driving Profitable Growth in Multiple Myeloma
Driving Profitable Growth in Multiple Myeloma Q3 2025 Commercial Highlights Net Product Revenue Grew 8.5% YoY • U.S. net product revenue was $32.0 million in Q3’25, up 8.5% from $29.5 million in Q3’24. $32.0M • Demand for XPOVIO was consistent in $29.5M Q3’25 compared to Q3’24, with the community se
Slide 16: Preparing for Myelofibrosis Commercial Launch
PREPARING FOR MYELOFIBROSIS COMMERCIAL LAUNCH ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 17: Clear Opportunity to Redefine Standard of Care Beyond JAKi Therapies
Clear Opportunity to Redefine Standard of Care Beyond JAKi Therapies No Novel Ruxolitinib, ≤35% Options Current SoC, Patients on Beyond JAKi Approved 14 Ruxolitinib Therapies Years Ago Achieve SVR351 1. Ruxolitinib-alone arms of SIMPLIFY-1 Study, 2017; MANIFEST-2 Study,ASH 2023; and Transform-1 Stud
Slide 18: Selinexor plus Ruxolitinib Could Deliver Up To ~$1B Annually in Net Sales at Peak
In a Multi-Billion Dollar U.S. Market1, Selinexor plus Ruxolitinib Combination Could Deliver Up To ~$1B Annually in Net Sales at Peak Incidence of Frontline Myelofibrosis Target Population High Intent-to-Treat Assumed Duration Prevalence1,2 (Intermediate-to-High Risk with with Combination5 of Therap
Slide 19: Well-Positioned for a Rapid and Successful Launch in Myelofibrosis
Well-Positioned for a Rapid and Successful Launch as Potentially the First Combination Therapy in Myelofibrosis Existing Capabilities to Significant Overlap Amongst Support Myelofibrosis Lauch Customers and Patients Patient Support Sales ~70% Hub of myelofibrosis patients are treated in a community
Slide 20: Financial Highlights
FINANCIAL HIGHLIGHTS Lori Macomber, CPA Chief Financial Officer and Treasurer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 21: Q3 2025 Financial Results and Guidance
Q3 2025 Financial Results and Guidance 3Q 3Q Statements of Operations ($ millions) 2025 2024 2025 Financial Guidance Total Revenue $44.0 $38.8 • Total Revenue of $140-$155 million XPOVIO Net Product Revenue 32.0 29.5 License and Other Revenue 12.0 9.3 • U.S. XPOVIO Net Product Revenue of $110-$120 m
Slide 22: Closing Remarks
CLOSING REMARKS Richard Paulson President and Chief Executive Officer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 23: Positioned to Execute on Potentially Transformative Opportunities
Positioned to Execute on Potentially Transformative Opportunities Endometrial Commercial Financial Myelofibrosis Cancer Foundation Discipline Top-Line Data from Top-Line Data from Profitable Multiple Cash Runway Phase 3 SENTRY Phase 3 XPORT-EC Myeloma into 2Q 2026 Expected March Expected Mid-2026 Fr
Slide 24: Appendix
APPENDIX ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 25: 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 26: XPORT-EC-042 Phase 3 Trial of Selinexor Maintenance Therapy in Endometrial Cancer
XPORT-EC-042* Phase 3, Randomized, Double-Blind Trial of Selinexor as Maintenance Therapy for Patients with TP53wt, Advanced or Recurrent EC TP53 Wild-Type Status is Assessed by Companion Diagnostic Partner Foundation Medicine2 Study is Actively Enrolling in Collaboration with ENGOT3 and GOG4 Planne
Slide 27: Phase 3 Global Study (XPORT-MM-031/EMN29) Evaluating SPd in Multiple Myeloma
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
Slide 28: 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 Selinexor 60 mg QW • SVR35 at week 24 JAKi naïve Patients with Myelofibrosis (n=29) Key Secondary Endpoints (n=58) • TSS50 at week 241 Selinexor 40 mg QW P
Slide 29: Rapid and Deep SVR35 Achieved with Selinexor + Ruxolitinib in Phase 1 Trial
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
Slide 30: Sustained Responses with No Progressions for SVR35 or TSS50 Responders
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
Slide 31: 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
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