Karyopharm Therapeutics Inc. · NASDAQ:KPTI

Karyopharm Therapeutics — Q4 2025 Earnings Presentation

35 slides from Karyopharm Therapeutics's earnings presentation, Feb 12, 2026

Slide 1: Fourth Quarter 2025 Financial Results & Business Update
Fourth Quarter 2025 Financial Results & Business Update February 12, 2026
Slide 2: On Today’s Call
On Today’s Call • Welcome Brendan Strong, SVP, Investor Relations • Overview Richard Paulson, President and Chief Executive Officer • Pipeline Update Dr. Reshma Rangwala, Chief Medical Officer and Head of Research • Commercial Highlights and Myelofibrosis Commercial Opportunity Sohanya Cheng, Chief
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 2026 total revenue, 2026 U
Slide 5: 2026 has the Promise to be a Transformative Year for Karyopharm
2026 has the Promise to be a Transformative Year for Karyopharm and the Patient Communities that we Intend to Serve XPOVIO® (selinexor) has a Growing Global Demand Myelofibrosis Peak Novel & Differentiated MoA for XPOVIO/NEXPOVIO® Annual Revenue that has the Potential to (selinexor); Now Approved in
Slide 6: Pipeline Update
PIPELINE UPDATE Reshma Rangwala, MD, PhD Chief Medical Officer and Head of Research ©2026 KARYOPHARM THERAPEUTICS INC.
Slide 8: 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 9: 7+ Years of Data 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 10: XPO1 Inhibition is a Multifaceted Approach to Inhibiting 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 11: 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 12: SENTRY Phase 3 Trial of Selinexor in Combination with Ruxolitinib
SENTRY (XPORT-MF-034*) Phase 3 Trial of Selinexor in Combination with Ruxolitinib in JAKi-Naïve Myelofibrosis Enrollment Completed September 2025 Ruxolitinib1 BID + Selinexor 60 mg QW Primary Endpoints JAKi-naïve Patients (tested sequentially) with Myelofibrosis (28-day cycle) R SVR35 week 243 (N=35
Slide 13: Significant Opportunity to Expand into other MPNs
Significant Opportunity to Expand into other MPNs Opportunity to expand XPO1 inhibition across Eltanexor is positioned other MPNs1 (PV & ET) to be our leading with eltanexor, pending next generation positive data from our XPO1 inhibitor in Phase 3 SENTRY Trial in MF MPNs2 1. Myeloproliferative neopl
Slide 15: 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 population4-6 of overall EC population4-6 *NCT05611931 TP53wt > 50% Molecular characterization is used t
Slide 16: SIENDO Longer-Term Follow Up: Median PFS 28.4 Months in TP53 Wild-Type
Longer-Term Follow Up from SIENDO Shows Encouraging Signal of Improving Median PFS Benefit to 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 0.7
Slide 17: SIENDO Longer-Term Follow Up: Median PFS 39.5 Months in TP53wt/pMMR
Longer-Term Follow Up from SIENDO Shows Encouraging Signal of Improving Median PFS Benefit to 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 no
Slide 18: Treatment Emergent Adverse Events from Longer-Term Follow-Up of 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
Slide 19: 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 TP53 Wild-Type Status is Assessed by Companion Diagnostic Partner Foundation Medicine2 Study is Actively Enrolling in Collaboration with ENGOT3 and GOG4 Planne
Slide 20: Commercial Highlights
COMMERCIAL HIGHLIGHTS Sohanya Cheng Chief Commercial Officer and Head of Business Development ©2026 KARYOPHARM THERAPEUTICS INC.
Slide 21: Driving Profitable Growth in Multiple Myeloma: 2025 Commercial Highlights
Driving Profitable Growth in Multiple Myeloma 2025 Commercial Highlights Net Product Revenue • U.S. XPOVIO net product revenue was ~$115 million and ~$32 million in FY 2025 $115M and 4Q’25, respectively. $113M • Demand for XPOVIO was consistent in 2025 to 2024 with the community setting continuing t
Slide 22: Preparing for Myelofibrosis Commercial Launch
PREPARING FOR MYELOFIBROSIS COMMERCIAL LAUNCH ©2026 KARYOPHARM THERAPEUTICS INC.
Slide 23: 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 Stud
Slide 24: Selinexor plus Ruxolitinib Could Deliver Up To ~$1B Annually at Peak
In a Multi-Billion Dollar U.S. Market1, Selinexor plus Ruxolitinib Combination Could Deliver Up To ~$1B Annually in Net Sales at Peak Incidence of Frontline Myelofibrosis Target Population High Intent-to-Treat Assumed Duration Prevalence1,2 (Intermediate-to-High Risk with with Combination5 of Therap
Slide 25: Established Commercial and Medical Affairs Leadership
Established Commercial and Medical Affairs Leadership with Deep Hematological Oncology and Rare Disease Experience Amama Sadiq MD, MPH SVP, Global Medical & Scientific Affairs Scientific & Medical Affairs Richard Paulson President and CEO Tim Suchanek SVP, National Sales Existing Sales Capabilities
Slide 26: Positioning for Targeted Launch Covering 100% of Key Accounts
Positioning for Targeted Launch with Commercial Organization Covering 100% of Key Accounts Academic Community >70% of patients treated at Top 50 academic institutions1 Majority of patients U.S. treated in Myelofibrosis five large Community Majority of the 30% Patients Treated by Setting 70% Networks
Slide 27: Opportunity to Rapidly Transform Frontline Myelofibrosis Treatment Landscape
Opportunity to Rapidly Transform Frontline Myelofibrosis Treatment Landscape with Selinexor plus Ruxolitinib Significant Highly compelling Concentrated Aligns with unmet need with and convenient account base existing physician two-thirds1 of patients all-oral product profile targeted with workflow w
Slide 28: Financial Highlights
FINANCIAL HIGHLIGHTS Lori Macomber, CPA Chief Financial Officer and Treasurer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 29: Q4 and Full Year 2025 Financial Results and 2026 Guidance
Q4 and Full Year 2025 Financial Results and 2026 Guidance 4Q 4Q Statements of Operations ($ millions) 2025 2024 2025 2024 2026 Financial Guidance1 Total Revenue $34.1 $30.5 $146.1 $145.2 • Total Revenue of $130-$150 million XPOVIO Net Product Revenue 32.1 29.3 114.9 112.8 License and Other Revenue 2
Slide 30: Closing Remarks
CLOSING REMARKS Richard Paulson President and Chief Executive Officer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 31: Positioned to Execute on Potentially Transformative Opportunities
Positioned to Execute on Potentially Transformative Opportunities Phase 3 Phase 3 Commercialization SENTRY XPORT-EC-042 Capabilities Top-Line Data from Top-Line Data from Existing Phase 3 SENTRY Phase 3 Trial in Commercialization Trial in Endometrial Capabilities Myelofibrosis Cancer Expected Positi
Slide 33: Top-Line Data from Two Phase 3 Trials Anticipated in 2026
Top-Line Data from Two Potentially Transformative Phase 3 Trials Anticipated in 2026 – Opportunity to Expand beyond MF to other MPNs Indication Early Stage Mid Stage Late Stage Commercial Multiple myeloma (penta-refractory) w/dexamethasone Multiple myeloma (2L+) w/bortezomib + dexamethasone DLBCL (R
Slide 34: 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) • Abs-TSS at week 241 Selinexor 40 mg QW
Slide 35: 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

Karyopharm Therapeutics — Q4 2025 Earnings Presentation on 6ix

Karyopharm Therapeutics — Q4 2025 Earnings Presentation

Slide 1: Fourth Quarter 2025 Financial Results & Business Update

Slide 2: On Today’s Call

Slide 3: Forward-looking Statements and Other Important Information

Slide 4: Overview

Slide 5: 2026 has the Promise to be a Transformative Year for Karyopharm

Slide 6: Pipeline Update

Slide 7: Myelofibrosis

Slide 8: Myelofibrosis Is a Rare Blood Cancer Defined by Four Hallmarks

Slide 9: 7+ Years of Data in Myelofibrosis

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

Slide 11: Selinexor plus Ruxolitinib May Potentially Establish a New Paradigm

Slide 12: SENTRY Phase 3 Trial of Selinexor in Combination with Ruxolitinib

Slide 13: Significant Opportunity to Expand into other MPNs

Slide 14: Endometrial Cancer

Slide 15: Phase 3 XPORT-EC-042 Trial Focused on Patients with TP53wt EC

Slide 16: SIENDO Longer-Term Follow Up: Median PFS 28.4 Months in TP53 Wild-Type

Slide 17: SIENDO Longer-Term Follow Up: Median PFS 39.5 Months in TP53wt/pMMR

Slide 18: Treatment Emergent Adverse Events from Longer-Term Follow-Up of TP53wt Subgroup

Slide 19: XPORT-EC-042 Phase 3 Trial of Selinexor as Maintenance Therapy

Slide 20: Commercial Highlights

Slide 21: Driving Profitable Growth in Multiple Myeloma: 2025 Commercial Highlights

Slide 22: Preparing for Myelofibrosis Commercial Launch

Slide 23: No Novel Options Beyond JAKi

Slide 24: Selinexor plus Ruxolitinib Could Deliver Up To ~$1B Annually at Peak

Slide 25: Established Commercial and Medical Affairs Leadership

Slide 26: Positioning for Targeted Launch Covering 100% of Key Accounts

Slide 27: Opportunity to Rapidly Transform Frontline Myelofibrosis Treatment Landscape

Slide 28: Financial Highlights

Slide 29: Q4 and Full Year 2025 Financial Results and 2026 Guidance

Slide 30: Closing Remarks

Slide 31: Positioned to Execute on Potentially Transformative Opportunities

Slide 32: Appendix

Slide 33: Top-Line Data from Two Phase 3 Trials Anticipated in 2026

Slide 34: SENTRY-2 Phase 2 Trial of Selinexor Monotherapy in JAKi-Naïve MF

Slide 35: Phase 3 Global Study (XPORT-MM-031/EMN29) Evaluating SPd in Multiple Myeloma