Karyopharm Therapeutics : 1Q26 Earnings Presentation

Published: 2026-05-14 08:08:09 ET KPTI

Published on 05/14/2026 at 08:08 am EDT

First Quarter 2026 Financial Results & Business Update

May 14, 2026

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 Endometrial Cancer Opportunity

Sohanya Cheng, Chief Commercial Officer

and Head of Business Development

Financial Results and Guidance

Lori Macomber, Chief Financial Officer and Treasurer

Closing Remarks

Richard Paulson, President and Chief Executive Officer

Q&A Session

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.S. net product revenue, 2026 R&D and SG&A expenses, expected cash runway and liquidity; Karyopharm's beliefs about the market opportunity and annual peak revenue opportunities for selinexor; expectations with respect to commercialization efforts; expectations regarding the timing of reporting topline data, publications or compendia listing related to ongoing clinical trials; the ability of selinexor and eltanexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, and other diseases; expectations with respect to the clinical development plans and potential regulatory submissions of selinexor; the potential manuscript submission for publication; and the potential inclusion of the combination of selinexor and ruxolitinib in relevant compendia. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this presentation could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical and preclinical trials, including subsequent analysis of existing data and new data received from ongoing and future trials; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical trials; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; substantial doubt exists regarding Karyopharm's ability to continue as a going concern; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Annual Report on Form 10-K for the year ended December 31, 2025, which was filed with the Securities and Exchange Commission (SEC) on February 13, 2026, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this presentation speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Karyopharm regularly uses its website to post information regarding its business, drug development programs and governance. Karyopharm encourages investors to use https://www.karyopharm.com, particularly the information in the section entitled "Investors," as a source of information about Karyopharm. References to https://www.karyopharm.com in this presentation are not intended to, nor shall they be deemed to, incorporate information on https://www.karyopharm.com into this presentation by reference. Other than the currently approved indications of XPOVIO, selinexor is an investigational drug that has not been approved by the FDA or any other regulatory agency, and the safety and efficacy of this drug has not been established by any agency.

XPOVIO® (selinexor) and NEXPOVIO® (selinexor) are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this presentation are the property of their respective owners. All rights reserved.

OVERVIEW

Richard Paulson

President and Chief Executive Officer

XPOVIO® (selinexor) has a Novel & Differentiated MoA that has the Potential to Treat Various Cancers1

Growing Global Demand

for XPOVIO/NEXPOVIO®

(selinexor); Now Approved in more than 50 Countries

Multi-Billion Dollar

U.S. Myelofibrosis and Endometrial Cancer

Markets2,3

Profitable, Commercial Organization in U.S. can be Leveraged Across Other Indications

Topline Data Reported in March 2026 from Phase 3 SENTRY trial; Encouraging Profile

Observed

Topline Data Expected in Mid-2026, from Phase 3 XPORT-EC-042

trial of Selinexor in Endometrial Cancer

1. Makker ASCO 2024; Tantravahi ASH 2023; Mechanism of Action (MoA). 2. Clarivate/DRG Myelofibrosis Disease Landscape report (accessed 2024). 3. Clarivate/DRG Endometrial Carcinoma Disease Landscape Report (accessed 2024).

PIPELINE UPDATE

Reshma Rangwala, MD, PhD

Chief Medical Officer and Head of Research

Nucleus

XPO1

RAN-GTP

RNA binding adaptor (e.g., elF4E)

Nuclear pore complex

Cytoplasm

Protein cargoes: e.g., tumor suppressor proteins and growth regulators like p53, p27, or FOXO family proteins1,2

RAN-GDP

(GTP hydrolysis)

RAN-GDP

(GTP hydrolysis)

RNA cargoes: e.g., oncoprotein mRNA like MYC3

Selinexor and Eltanexor (XPO1 Inhibitors) selectively inhibit the export of multiple macromolecules from the nucleus to the cytoplasm

Increases nuclear levels of tumor suppressor proteins and their activation4,5

Traps oncoprotein mRNA in the nucleus,

leading to reduced oncoprotein levels6

Retains activated glucocorticoid receptor in the nucleus, leading to altered expression of genes involved in inflammatory pathways7

Reduced proliferation and

increased apoptosis of

XPO1

Inhibitor

Exportin 1 (XPO1) transports proteins and

protein-RNA complexes out of the nucleus

Adapted from Azizian NG, et al (2020)

cancer cells8

Nucleus

MYC, MYC proto-oncogene; eIF4E, Eukaryotic translation initiation factor 4E; FOXO, forkhead box, sub-group O; p27, cyclin-dependent kinase inhibitor 1B; p53, tumor protein 53; RAN, RAS-related nuclear protein; GDP, guanosine diphosphate; GTP, guanosine triphosphate

1. Azizian NG, et al. J Hematol Oncol. 2020;13(1):61. doi:10.1186/s13045-020-00903-4; 2. Das A, et al. Exp Hematol Oncol. 2015;4:7. doi:10.1186/s40164-015-0002-5.; 3. Culjkovic-Kraljacic B. Cell Rep. 2012;2(2): 207-15. doi: 10.1016/j.celrep.2012.07.007. 4. Turner JG, et al. Biochem Pharmacol. 2012 Apr 15;83(8):1021-32. doi: 10.1016/j.bcp.2011.12.016. 5. Azmi AS, et al. Nat Rev Clin Oncol. 2021 Mar;18(3):152-169. doi: 10.1038/s41571-020-00442-4. 6 Kashyap T et al, Oncotarget. 2018 Jul 20;9(56):30773-30786. doi: 10.18632/oncotarget.25637; 7. Argueta C, et al. Oncotarget. 2018 May 22;9(39):25529-25544. doi: 10.18632/oncotarget.25368. doi:10.1016/j.clml.2018.03.003; 8. Sun Q, et al. Signal Transduct Target Ther. 2016;1:16010. doi:10.1038/sigtrans.2016.10

Opportunity to Improve Outcomes Four Hallmarks of Myelofibrosis

Low rates of SVR351

No novel mechanisms beyond JAK

inhibitors

Median survival of patients with

intermediate-to-high risk myelofibrosis is 4 to 5 years4,8

Minimal evidence of disease

modification9

Bone Marrow Fibrosis3

Enlarged Spleen5

Constitutional Symptoms2,6,7

Abnormal Blood Cell Production3

1. Ruxolitinib-alone arms of SIMPLIFY-1 Study, 2017; MANIFEST-2 Study,ASH 2023; and Transform-1 Study ASH 2023 2. Tefferi A. Am J Hematol. 2023;98:801-821. 3. O'Sullivan JM, Harrison CN. Clin Adv Hematol Oncol. 2018;16(2):121-131.

Passamonti F, et al. Blood. 2010;115(9):1703-1708. 5. Vannuchi A, et al. Haematologica. 2015;100(9):1139-1145. 6. Mesa R, et al. Leuk Res. 2009;33(9):1199-1203. 7. Mitra D, et al. Cancer Med. 2013;2(6):889-898. 8. Data on File; internal analysis of published MF trial data. 9. Pemmaraju et. al Cancer 2022.

Co-Primary Endpoint

Statistically Significant

Rapid, Near-Doubling

and Sustained SVR35 Rates Compared to Ruxolitinib

Co-Primary Endpoint

Not Statistically Significant

Similar Improvement

in Symptoms Compared to Ruxolitinib

Secondary Endpoint

Nominally Significant

Promising Signal of

Overall Survival Compared to

Ruxolitinib

Pre-Specified Exploratory Endpoint

VAF Reduction Suggests Evidence of Potential Disease Modification

SENTRY Supports Selinexor's Potential Role in Myelofibrosis

High Unmet Need with One Approved Class of Therapy

Engage with FDA & Global Regulatory Agencies on Data and Filing Plans

Late-Breaking Oral Presentation at ASCO

Publication of Manuscript Anticipated Mid-2026 Potential Compendia Inclusion in 2H'26

pMMR1 ~80%

of overall EC population5-7

dMMR1 ~20%

of overall EC population5-7

*NCT05611931

TP53wt > 50%

Molecular characterization is the standard today to inform treatment decisions for patients with EC, yet there are currently no approved therapies specifically targeting TP53wt EC patients1-4

The safety and efficacy of selinexor in endometrial cancer has not been established and has not been approved by the U.S. FDA or any other regulatory authority for use in endometrial cancer.

EC, endometrial cancer; dMMR, deficient mismatch repair; pMMR, proficient mismatch repair; TP53, tumor protein 53 gene; wt, wild-type

1. Tronconi F, et al. Crit Rev Oncol Hematol. 2022;180:103851. 2. Levine DA. Nature. 2013;497(7447):67-73. 3. Oaknin A, et al. Ann Oncol. 2022;33:860-877. 4. Secord AA, et al. Obstetrics & Gynecology 2025 Nov 1:146(5):660-671.

Leslie KK, et al. Gynecol Oncol. 2021;161(1):113-121. 6. Mirza MR, et al. Presentation at: ESMO Congress; October 20-24, 2023. 7. Vergote I, et al. Presentation at: European Society for Medical Oncology Virtual Plenary; March 17-18, 2022;

Abstract VP2-2022; Vergote I, et al J Clin Oncol. 2023;41(35):5400-5410.

TP53 Wild-Type EC and Establish a New Standard of Care in TP53wt/pMMR

No Personalized Biomarker-Driven Maintenance Therapies in EC

CPIs May Deliver Less Benefit in the TP53wt/pMMR1,2

Subgroup with PFS Hazard Ratio of 0.773

Urgency to Establish a TP53wt Directed Therapy

1. Oaknin A, et al. Ann Oncol. 2022;33:860-877 2. Mirza MR, et al. Presentation at: ESMO Congress; October 20-24, 2023; 3. ESMO Annals of Oncology, Volume 34, Supplement 2, S507, October 2023.

TP53 Wild-Type Subgroup Compared to 3.7 Months for Patients on Placebo1

Selinexor: 13.7 months; Placebo: 3.7 months

HR = 0.41 (95% CI 0.23-0.72)

Two-sided nominal P value = 0.002

The safety and efficacy of selinexor in endometrial cancer has not been established and has not been approved by the U.S. FDA or any other regulatory authority.

Data from a pre-specified exploratory subgroup from the Phase 3 SIENDO trial in endometrial cancer (Vergote, I., et al. Journal of Clinical Oncology, December 2023).

PFS calculation begins at initiation of maintenance therapy

36.8 months of follow up

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

1.00

Probability of PFS

0.75

0.50

0.25

0.00

No. at risk

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51

Months

Selinexor

Placebo

The safety and efficacy of selinexor in endometrial cancer has not been established and has not been approved by the U.S. FDA or any other regulatory authority.

Data cutoff date: April 1, 2024

HR, hazard ratio; NR, not reached.

Molecular status determined by sequencing (TP53 WT, n=99; TP53 mutant, n=97) and if NGS not available, by immunohistochemistry (TP53 WT, n=14; TP53 mutant, n=29).

Data from a pre-specified exploratory subgroup from the Phase 3 SIENDO trial in endometrial cancer (Makker V, et al. Presented at ASCO Annual Meeting May 29-June 22, Chicago, IL).

TP53 Wild-Type/pMMR Subgroup; Longer-Term Follow Up from SIENDO

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

HR: 0.36 (95% CI 0.19-0.71), One-sided nominal P-value = 0.0011

PFS calculation begins at initiation of maintenance therapy.

+ Placebo

38.5 months of follow up

1.00

Probability of PFS

0.75

0.50

0.25

0.00

No. at risk

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51

Months

Selinexor

Placebo

The safety and efficacy of selinexor in endometrial cancer has not been established and has not been approved by the U.S. FDA or any other regulatory authority.

Data cutoff date: April 1, 2024

Molecular status determined by sequencing (TP53 WT, n=99; TP53 mutant, n=97; pMMR, n=164) and if NGS not available, by immunohistochemistry (TP53 WT, n=14; TP53 mutant, n=29; pMMR, n=20).

1. Data from a pre-specified exploratory subgroup from the Phase 3 SIENDO trial in endometrial cancer (Makker V, et al. Presented at ASCO Annual Meeting May 29-June 22, Chicago, IL).

TP53wt Subgroup in the Phase 3 SIENDO Trial in Endometrial Cancer1

Selinexor (n=76*)

Placebo (n=35*)

Nausea Vomiting Diarrhea

90%

60%

45%

13%

14%

40%

37%

Constipation

Asthenia Fatigue Thrombocytopenia Decreased appetite

Neutropenia

Anemia

33%

36%

42%

36%

34%

33%

10%

20%

6% 40%

26%

20%

Any grade in ≥20% patients Grade ≥3

Abdominal pain

TEAEs leading to discontinuation† TRAEs leading to discontinuation

26%

17% 7%

16% 5%

17%

‡

TEAEs leading to death

0 3%

120

100 80 60 40 20 0 20 40 60 80 100

Percent

The safety and efficacy of selinexor in endometrial cancer has not been established and has not been approved by the U.S. FDA or any other regulatory authority for use in endometrial cancer.

1. Data cutoff date: April 1, 2024; Makker V, et al. Presented at ASCO Annual Meeting May 29-June 22, 2024, Chicago, IL TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event.

*Two patients total did not receive treatment (n=1, selinexor; n=1, placebo) and were excluded from this analysis.

†Reasons for discontinuation: nausea (n=5), fatigue (n=3), vomiting (n=3), asthenia, cataract, general physical health deterioration, ileus, neutropenia (all n=1).

‡Reason for death unknown/missing.

Enrollment Completed: Study Conducted in Collaboration with ENGOT3 and GOG4

1:1

Placebo orally QW Until PD, toxicity, or 3 years

Selinexor 60 mg orally QW Until PD, toxicity, or 3 years

Final Enrollment

(N=257)6

Patients aged ≥18 years with

Known TP53wt EC by central NGS2

Patients w/ TP53wt/dMMR tumors must be medically ineligible to receive checkpoint inhibitors1

Primary Stage IV disease or first recurrent EC

Received ≥12 weeks of platinum-based

chemotherapy ± immunotherapy

Primary Endpoint5

PFS assessed by investigator

PFS mITT (N ~220)6 PFS ITT (N=257)6

*NCT05611931

The safety and efficacy of selinexor in endometrial cancer has not been established and has not been approved by the U.S. FDA or any other regulatory authority.

Populations tested sequentially

Randomization stratified by:

Response upon completion of platinum-based therapy: CR vs. PR

Primary stage IV vs recurrent EC

Patient populations defined as:

mITT population: A/R EC patients whose tumors are a) TP53wt/non-MSI-H (pMMR) EC, or b) A/R EC patients whose tumors are TP53wt/MSI-H (dMMR) and medically ineligible to receive checkpoint inhibitors

ITT population A/R EC patients whose tumors are TP53wt

Topline data anticipated mid-2026

A/R, advanced/recurrent; PFS, progression-free survival; PD, progressive disease; QW, every week; NGS, Next Generation Sequencing. 1. Based on amended study design; amendment incorporating these changes has been submitted to the FDA and the respective regulatory authorities globally; 2. Utilizing Foundation Medicine's tissue-based comprehensive genomic profiling test to identify TP53 status. 3. European Network for Gynaecological Oncological Trial groups. 4. Gynecologic Oncology (GOG) Foundation. 5. The primary PFS analysis will be triggered once ~101 PFS events have been observed in the modified intent-to-treat (mITT) population. 6. mITT and ITT are powered >80% based upon a one-sided alpha of 0.025 and a target PFS HR of 0.55. Median PFS times for the placebo and selinexor arms are assumed to be 5.0 and 9.1 months, respectively; mITT final trial enrollment expected to be ~220 and ITT enrollment is 257.

COMMERCIAL HIGHLIGHTS

Sohanya Cheng

Chief Commercial Officer and Head of Business

Development

Disclaimer

Karyopharm Therapeutics Inc. published this content on May 14, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 14, 2026 at 12:07 UTC.