Karyopharm Therapeutics Inc. · NASDAQ:KPTI

Karyopharm Therapeutics — Q1 2025 Earnings Presentation

41 slides from Karyopharm Therapeutics's earnings presentation, May 12, 2025

Slide 1: First Quarter 2025 Financial Results & Business Update
First Quarter 2025 Financial Results & Business Update May 12, 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 5: Focused on Transformative Myelofibrosis Opportunity in 2025
Focused on Transformative Myelofibrosis Opportunity in 2025 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 Opportunity of up to Treat Various Cancers1 Over 45 Cou
Slide 6: Data Suggest Single-Agent Activity & Disease Modification from Randomized Phase 2 Trial
Data Suggest Single-Agent Activity & Disease Modification from Randomized Phase 2 Trial in Heavily Pre-Treated, Hard-to-Treat Myelofibrosis Phase 2 XPORT-MF-035 Selinexor vs. Physician's Choice (Primarily Ruxolitinib) in Previously Treated Myelofibrosis Single-Agent Clinical Lower Rates of All Activ
Slide 7: Delivering for Myelofibrosis Patients
Efficient Development Spanning Seven Years, Consistently Building a Strong Profile for Potential Success in Myelofibrosis Executing Phase 3 SENTRY trial with quality and speed, faster than historical benchmarks Delivering for Phase 2 in JAKi pre-treated patients further demonstrates evidence of mono
Slide 8: 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
Slide 9: 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 10: Pipeline Update
PIPELINE UPDATE Reshma Rangwala, MD, PhD Chief Medical Officer and Head of Research ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 11: 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 12: 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* Four Key Pillars in Myelofibrosis Safety Spleen Symptom Hemoglobin Disease Improving Volume Improvement Stabilization4 Modification Safety Profile with Selinexo
Slide 13: XPORT-MF-035: Single Agent Selinexor Versus Physician's Choice
XPORT-MF-0351: A Phase 2 Study of 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,
Slide 14: Demographics and Baseline Disease Characteristics were 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 Selinexor PC Total Selinexor PC Total Characteristic N=12 N=12 N=24 Characteristic N=12 N=12 N=24 Age, years, median (min, max) 70 (43, 78) 71 (60,
Slide 15: Spleen Volume Reduction Rates More than Double with Selinexor
Spleen Volume Reduction Rates More than Double with Selinexor Compared to Physician's Choice* in Efficacy Evaluable Population Physician's Choice (PC) Treated Selinexor Treated 50 Randomized to Selinexor Crossover to Selinexor 39.7 Reduction at Any Time (%) Maximum Spleen Volume 32.2 26.3 25 11.7 1.
Slide 16: Patients Who Progressed on Physician's Choice 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 Spleen Volume 50 Reduction at Any Time (%) Maximum Spleen Volume 25 • All patients that crossed over to selinexor had a substantial spleen reduction 0 • 4/5 patients
Slide 17: Robust Symptom Improvement Assessed by TSS50 and Abs-TSS
Robust Symptom Improvement Assessed by TSS50 and Abs-TSS Observed with Selinexor Monotherapy in Efficacy Evaluable Population All Selinexor Treated PC (n=9) Selinexor (n=7) Patients*** (n=11) TSS50 at Week 24* 0 2 (28.6%) 2 (18.2%) Baseline TSS, Mean (SD) 17.28 (17.100) 18.80 (15.579) 17.64 (15.494)
Slide 18: Hemoglobin Levels Meaningfully Higher with Selinexor
Hemoglobin Levels Meaningfully Higher with Selinexor Compared to Physician's Choice Arm At data cutoff, mean HgB value was higher in the selinexor arm compared to physician’s choice (+ 1.7% vs −26.7%) Data cut 2024.10.31 ©2025 KARYOPHARM THERAPEUTICS INC. 18
Slide 19: Selinexor Meaningfully Decreased Transfusion Burden by ~50%
Selinexor Meaningfully Decreased Transfusion Burden by ~50% 1 Red Blood Cell Transfusions Received: 1 5/12 (SEL) vs 9/12 (PC) pts Avg Units Total Transfused Arm n Transfused Months Units Per 1 Month * Patient 0017-001 only got 1 dose but was later transfused with 9 units. This patient is excluded. P
Slide 20: Key Cytokines Relevant to Myelofibrosis Pathogenesis, Anemia and Symptom Development
Key Cytokines Relevant to Myelofibrosis Pathogenesis, Anemia and Symptom Development all Mediated Through NF-kB Malignant Mutated Clonal Expansion, • IL-6 MF Pathogenesis Hepatosplenomegaly and Bone Marrow • IL-8 Angiogenesis1,2 • IL-6 Constitutional Symptoms Drives Inflammation3,4 • IL-8 • TNF Sup
Slide 21: Selinexor Induced Rapid and Substantial Reduction in Cytokines
Selinexor Induced Rapid and Substantial Reduction in Cytokines Relevant to MF Pathogenesis, Symptom Development and Anemia Key cytokines relevant to symptom development and MF pathogenesis. Cytokines reduced by selinexor but not PC • Increase Selinexor (5) • Decrease PC (Rux) (5) IL8 Cytokines assoc
Slide 22: Manageable Safety Profile with No TEAEs Leading to Treatment Discontinuation
Manageable Safety Profile with No TEAEs Leading to Treatment Discontinuation 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%
Slide 23: SENTRY Phase 3 Trial of Selinexor plus Ruxolitinib in JAKi Naïve Myelofibrosis
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 Abs-TSS Replaced TSS50 as a Co-Primary Endpoint Study is Actively Enrolling Ruxolitinib1 BID + JAKi naïve Selinexor 60 mg QW Prim
Slide 25: Focusing Phase 3 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 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 26: Updated 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 28: Phase 3 Global 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 29: Commercial Highlights
COMMERCIAL HIGHLIGHTS Sohanya Cheng Chief Commercial Officer and Head of Business Development ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 30: Demand Growth Q1'25 YoY; Q1 2025 Highlights
Demand Growth Q1’25 YoY; Q1 2025 Highlights Net Product Revenue Primarily Impacted by Atypical Returns of Expired Units • 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 retu
Slide 31: 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
Slide 32: Selinexor Potential to Deliver Up to ~$1 Billion in Annual U.S. Peak Revenue
Selinexor has the Potential to Deliver Up to ~$1 Billion in Annual U.S. Peak Revenue1 as the First Approved Combination Therapy in JAKi Naïve Myelofibrosis Global Market Prevalence Newly Diagnosed Patients in the U.S. Annually INCIDENCE ✓ ~ 20,000 living with MF in the U.S.2 1L JAKi Naive4 ~7K ✓ ~17
Slide 33: Well-Positioned for a Rapid and Successful Launch in Myelofibrosis
Well-Positioned for a Rapid and Successful Launch as Potentially the First Approved Combination Therapy in Myelofibrosis1 Significant Need Compelling Target Synergistic Customer Experienced to Improve SoC Product Profile Base Cross-Functional Hematology Team Less than half of First to market combina
Slide 34: Endometrial Cancer: Potential to be the First Novel Oral Maintenance Therapy
Endometrial Cancer: Potential to be the First Novel Oral Maintenance Therapy in TP53 Wild-Type Endometrial Cancer Addressable Market Opportunity in the U.S. Key Commercial Success Factors INCIDENCE First novel, biomarker-specific oral 1L Advanced/Recurrent1 1 maintenance therapy7 pMMR1 ~80% dMMR1 ~2
Slide 35: Financial Highlights
FINANCIAL HIGHLIGHTS Lori Macomber, CPA Chief Financial Officer and Treasurer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 36: Q1 2025 Financial Results and Guidance
Q1 2025 Financial Results and Guidance 1Q 1Q Statements of Operations ($ millions) 2025 2024 2025 Financial Guidance Total Revenue $30.0 $33.1 • Total Revenue of $140-$155 million XPOVIO Net Product Revenue 21.1 26.0 License and Other Revenue 9.0 7.1 • U.S. XPOVIO Net Product Revenue of $115-$130 mi
Slide 37: Closing Remarks
CLOSING REMARKS Richard Paulson President and Chief Executive Officer ©2025 KARYOPHARM THERAPEUTICS INC.
Slide 38: 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 late 25/early 26; Potentially Myeloma Marketplace and Data from the Phase 2 Transformative Opportunity to Dri
Slide 40: 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
Slide 41: 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

Karyopharm Therapeutics — Q1 2025 Earnings Presentation on 6ix

Karyopharm Therapeutics — Q1 2025 Earnings Presentation

Slide 1: First 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: Focused on Transformative Myelofibrosis Opportunity in 2025

Slide 6: Data Suggest Single-Agent Activity & Disease Modification from Randomized Phase 2 Trial

Slide 7: Delivering for Myelofibrosis Patients

Slide 8: Believers in Selinexor's Potential to Improve Outcomes for Patients

Slide 9: Myelofibrosis Represents a Transformative Opportunity

Slide 10: Pipeline Update

Slide 11: XPO1 Inhibition is Potentially a Fundamental Mechanism in Myelofibrosis

Slide 12: Selinexor plus Ruxolitinib May Potentially Establish a New Paradigm

Slide 13: XPORT-MF-035: Single Agent Selinexor Versus Physician's Choice

Slide 14: Demographics and Baseline Disease Characteristics were Similar Across the Two Arms

Slide 15: Spleen Volume Reduction Rates More than Double with Selinexor

Slide 16: Patients Who Progressed on Physician's Choice Showed Meaningful Spleen Volume Reduction

Slide 17: Robust Symptom Improvement Assessed by TSS50 and Abs-TSS

Slide 18: Hemoglobin Levels Meaningfully Higher with Selinexor

Slide 19: Selinexor Meaningfully Decreased Transfusion Burden by ~50%

Slide 20: Key Cytokines Relevant to Myelofibrosis Pathogenesis, Anemia and Symptom Development

Slide 21: Selinexor Induced Rapid and Substantial Reduction in Cytokines

Slide 22: Manageable Safety Profile with No TEAEs Leading to Treatment Discontinuation

Slide 23: SENTRY Phase 3 Trial of Selinexor plus Ruxolitinib in JAKi Naïve Myelofibrosis

Slide 24: Endometrial Cancer

Slide 25: Focusing Phase 3 XPORT-EC-042 Trial on Patients with TP53wt EC

Slide 26: Updated XPORT-EC-042 Phase 3 Trial of Selinexor as Maintenance Therapy

Slide 27: Multiple Myeloma

Slide 28: Phase 3 Global Study Evaluating SPd in Previously Treated Multiple Myeloma

Slide 29: Commercial Highlights

Slide 30: Demand Growth Q1'25 YoY; Q1 2025 Highlights

Slide 31: Growing Global Demand for XPOVIO/NEXPOVIO

Slide 32: Selinexor Potential to Deliver Up to ~$1 Billion in Annual U.S. Peak Revenue

Slide 33: Well-Positioned for a Rapid and Successful Launch in Myelofibrosis

Slide 34: Endometrial Cancer: Potential to be the First Novel Oral Maintenance Therapy

Slide 35: Financial Highlights

Slide 36: Q1 2025 Financial Results and Guidance

Slide 37: Closing Remarks

Slide 38: 2025 Objectives and Milestones

Slide 39: Appendix

Slide 40: Focused High Potential Pipeline – Top Strategic Priority for 2025

Slide 41: Intellectual Property – Selinexor Protected by Global Patent Portfolio