Karyopharm Therapeutics : Corporate Presentation
KPTI
Published on 04/16/2026 at 07:24 am EDT
Corporate Presentation
April 2026
XPOVIO® (selinexor) has a Novel & Differentiated MoA that has the Potential to Treat Various Cancers1
for XPOVIO/NEXPOVIO®
(selinexor); Now Approved in more than 50 Countries
Observed
042 trial of Selinexor in Endometrial Cancer
1. Makker ASCO 2024; Tantravahi ASH 2023; Mechanism of Action (MoA). 2. Clarivate/DRG MF Landscape report (2023)
Indication
Early Stage
Mid Stage
Late Stage
Commercial
Multiple myeloma (penta-refractory) w/dexamethasone
Multiple myeloma (2L+)
w/bortezomib + dexamethasone
DLBCL (R/R) Monotherapy1
SELINEXOR
Myelofibrosis (JAKi naïve)
Topline Data Announced March 2026
Endometrial cancer (TP53 WT)
Topline Data Expected Mid-2026
Multiple myeloma (2L+ post-anti CD38)2
DLBCL (R/R)1
ELTANEXOR3
TBD (e.g. MPNs, TP53 wild-type solid tumors)
KPT-92743
Rhabdomyosarcoma / Ewings Sarcoma
KPT-3503
TBD
hematologic cancer solid tumor cancer
1. The FDA has requested the Company withdraw the accelerated approval of the DLBCL indication due to the Company's inability to complete the confirmatory trial. The Company has agreed with the FDA's request and will voluntarily withdraw the accelerated approval of the DLBCL indication in light of the feasibility of completing the confirmatory trial. As a result, the Company will cease ongoing and any further clinical development and related operational expenses in this indication. 2. EMN29 Study: Sponsored by European Myeloma Network. 3. Further development of the Company's early-stage pipeline is currently paused in line with prioritization of late-stage pipeline programs.
©2026 KARYOPHARM THERAPEUTICS INC.
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
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
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.
4. 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.
XPO1 Inhibition is a Multifaceted Approach to Inhibiting the Drivers of Myelofibrosis1-9
SEL
↓ Clonal cell division
↓ Splenomegaly
↓ Variant Allele Frequency (VAF)
↓ NFκB activity
↓ Cytopenias, fibrosis, constitutional symptoms
c-myc
XPO-1
c-myc
XPO-1
SEL
IκBα
Inflammatory cytokine / chemokine
Oncogene Oncogene mRNA
Tumor suppressor protein
↑ Apoptosis
IκBα
JAK-STAT
signaling
JAKi
JAK2 IL-6
SEL
JAKi
IκBα
Selinexor JAK inhibitor
↓ Variant Allele Frequency
(VAF)
p53
XPO-1
p53
NUCLEUS
SEL
CYTOPLASM
1. Yan D et al. Clin Cancer Res. 2019;25(7):2323-2335. 2. Kashyap T et al. Oncotarget. 2016;7(48):78883-78895. 3. Walker CJ et al. Blood. 2013;122(17):3034-3044. 4. Cheng Y et al. Mol Cancer Ther. 2014;13(3): 675-686. 5. Argueta C et al. Oncotarget. 2018;9(39);25529-25544. 6. Gandhi UH et al. Clin Lymphoma Myeloma Leukemia. 2018;18(5):335-345. 7. Garg M et al. Oncotarget. 2017;8(5):7521-7532. 8. Tan M et al. Am J Physiol Renal Physiol. 2014;307(11): F1179-1186. 9. Turner JG et al. Oncotarget. 2016;7(48):78896-78909.
(N=353)
Plt >100 x 109/L
R
Ruxolitiniba BID + Placebo
Ruxolitiniba BID + Selinexor 60 mg QW (28-day cycle)
Primary Endpoints
(tested sequentially)
SVR35 week 24c
+
Abs-TSS
week 24b,c,d
2:1
Select Secondary and
Exploratory Endpointse
Progression free survival
Overall survival
Hemoglobin stabilization
Variant allele frequency (VAF) reduction
Bone marrow fibrosis improvement
Changes in cytokine levels
*NCT04562389
Randomization stratified by:
Dynamic International Prognostic Scoring System (DIPSS) risk category intermediate -1 vs. intermediate -2 or high-risk
Spleen volume <1800 cm3 vs. >1800 cm3 by MRI/CT scan
Baseline platelet counts 100-200 x 109/ L vs. >200 x 109/L
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
a. Ruxolitinib dose based on platelet count per prescribing information. b. Evaluated by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. c. Both endpoints are powered at >80%; the assumptions for SVR35 is 40% for ruxolitinib and 70% for selinexor + ruxolitinib; assumptions for Abs-TSS are a >4-point delta and a standard deviation of 12 for both arms. d. Active symptoms of myelofibrosis as determined by presence of at least 2 symptoms using the MFSAF version 4.0. e. A sample of secondary and exploratory endpoints to be evaluated. Abs-TSS; absolute TSS; BID: Twice daily; JAKi, janus kinase inhibitors; Plt: Platelet; QW: Once weekly; SVR35: Spleen volume reduction ≥ 35%
Selinexor + Ruxolitinib (N = 235)
Placebo + Ruxolitinib (N = 118)
Spleen Volume Reduction
SVR35 at Week 24, n (%) 117 (49.8) 33 (28.0)
Exact 95% CI (43.2, 56.4) (20.1, 37.0)
Superior SVR35 at week 24
Difference in SVR35 at Week 24 (%) (Selinexor vs. Placebo)
21.82
of 50%, a near doubling compared to 28% with ruxolitinib monotherapy (p<0.0001)
95% CI (11.50, 32.14)
Cochran-Mantel-Haenszel Test (Selinexor vs. Placebo)
Odds Ratio (95% CI) 2.58 (1.60, 4.17)
One-Sided P-value <.0001
Data Cutoff Date: 2026-02-20
CI=Confidence Interval; SVR35=Spleen Volume Reduction of >=35%
Note: SVR35 at Week 24 is defined as proportion of patients with a >=35% reduction in spleen volume from baseline to Week 24, as measured by MRI or CT scan by Investigator assessment. Note: Cochran-Mantel-Haenszel test is stratified by randomization factors. Note: n is the number of patients with SVR assessments available.
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
Selinexor +
Ruxolitinib
Placebo +
Ruxolitinib
(N = 235)
(N = 118)
Spleen Volume Reduction SVR35 at Week 12, n (%)
116 (49.4)
24 (20.3)
SVR35 at Week 24, n (%)
117 (49.8)
33 (28.0)
Rapid SVR35 at week 12 of Patients Who Completed Week 36 or
207
100
49% compared to 20% with
ruxolitinib monotherapy
Sustained SVR35 at week 36 of 47% compared to 23% with ruxolitinib monotherapy
Discontinued Prior to Week 36
SVR35 at Week 36, n (%) [1] 97 (46.9) 23 (23.0)
SVR35 at Any Timepoint, n (%) 159 (67.7) 53 (44.9)
Exact 95% CI (61.3, 73.6) (35.7, 54.3)
Cochran-Mantel-Haenszel Test
(Selinexor vs. Placebo)
Odds Ratio (95% CI) 2.59 (1.64, 4.10)
Nominal One-Sided P-value <.0001
Data Cutoff Date: 2026-02-20
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
CI=Confidence Interval; SVR35=Spleen Volume Reduction of >=35%
Note: SVR35 at Week 12 and 24 allows +/- 21-day window. SVR35 at Week 36 and 48 allows +/- 28-day window. Note: SVR35 at any timepoint is defined as proportion of patients with a >=35% reduction in spleen volume from baseline to any post-baseline assessments regardless of visit window before new anti-MF therapy or disease progression. Note: Cochran-Mantel-Haenszel test is stratified by randomization factors.
[1] Denominator is the number of patients who completed the spleen assessment or discontinued the study prior to the specific timepoint.
10
0
-10
Mean(+/- SD)
-20
-30
-40
-50
-60
-70
-80
Selinexor + Ruxolitinib Placebo + Ruxolitinib
Selinexor + Ruxolitinib
Placebo + Ruxolitinib
235
118
199
102
186 98
134 76
94 53
Baseline Week 12 Week 24 Week 36 Week 48
Not all patients have been followed beyond week 24
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
Data Cutoff Date: 2026-02-20
Symptom Improvement
Similar levels of absolute TSS improvement from baseline in the selinexor plus ruxolitinib arm compared to ruxolitinib
n
235
117
Median
21.71
19.57
Mean
22.74 (11.877)
22.23 (13.031)
Mean (STD)
2.1 , 53.9
3.0 , 58.3
Week 24
Adjusted Absolute Mean Change
-9.89
-10.86
from Baseline (95% CI)
(-11.19, -8.59)
(-12.58, -9.14)
Adjusted Mean Difference
0.97
(Selinexor vs. Placebo) (95% CI)
(-1.07, 3.02)
One-sided P-value
0.8246
Baseline
Selinexor + Ruxolitinib (N = 235)
Placebo + Ruxolitinib (N = 118)
These differences were not statistically significant
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
Data Cutoff Date: 2026-02-20
CI=Confidence Interval; TSS=Total Symptom Score
Note: TSS is the sum of the 6 individual symptom scores included in the MFSAF v4.0, excluding fatigue. Each individual symptom score is on the 0-10 scale, and the TSS ranges from 0 to 60. A higher TSS indicates a higher disease burden and thus a worse outcome.
Note: Adjusted absolute mean change from baseline, adjusted mean difference, 95% CI and p-value are based upon mixed-
effects model for repeated measures (MMRM) adjusted for randomization stratification factors, sex and baseline TSS.
Note: n is the number of patients with TSS available.
The Company intends to continue to follow OS to maturity to further evaluate this signal
Overall Survival (OS) is a pre-
specified secondary endpoint
Hazard ratio of 0.43 and a nominal p-value of 0.0222
Post-hoc landmark analyses at
weeks 12 and 24 suggest SVR35 may predict overall survival
Selinexor + Ruxolitinib (N = 235)
Placebo + Ruxolitinib (N = 118)
Patients with Events, n 11 of 235 12 of 118
Percentage (%) 4.7 10.2
Median OS Follow-up Time (Months) [1] 11.56 12.58
95% CI (10.71, 13.01) (10.61, 13.93)
Overall Survival - Stratified Test [2]
Hazard Ratio (95% CI) [3] 0.43 (0.19, 1.00)
One-Sided Nominal P-value (log-rank)
0.0222
Data Cutoff Date: 2026-02-20 CI=Confidence Interval
Note: Overall Survival (OS) is defined as the duration from date of randomization to date of death due to any cause.
Based on reverse Kaplan-Meier method by swapping the censoring status.
Stratified by the randomization stratification factors.
Based on Cox Proportional Hazard model with Efron's method of handling ties.
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
VAF reduction was a prespecified exploratory endpoint
The proportion of patients who achieved a ≥20% VAF reduction at week 24
was greater with selinexor plus ruxolitinib compared to ruxolitinib alone
32%
Selinexor + Ruxolitinib Combination (n=1694)
VS
24%
Ruxolitinib (n=924)
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
1. Ross et. al Blood 2024. 2. Guglielmelli et. al AM J HEMATOL 2024 3. Deininger et al Blood 2015. 4. n= patients with VAF analysis at baseline and week 24 Data Cutoff Date: 2026-02-20
Selinexor +
Ruxolitinib
Placebo +
Ruxolitinib
(N = 234)
(N = 116)
n (%)
n (%)
All Grade TEAEs1
Thrombocytopenia
139 (59.4)
50 (43.1)
Anaemia
134 (57.3)
67 (57.8)
Nausea
134 (57.3)
20 (17.2)
Constipation
74 (31.6)
42 (36.2)
Neutropenia
63 (26.9)
10 (8.6)
Safety and tolerability is consistent
with the known profile of selinexor
and ruxolitinib individually
No new safety signals identified
Grade 3+ TEAEs 164 (70.1) 58 (50.0)
TEAEs Leading to Study Treatment Discontinuation
34 (14.5) 10 (8.6)
Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
The confirmed leukemic transformation rate was identical across both
treatment arms at 1.7%.
Selinexor is an FDA approved drug in certain indications, including multiple myeloma, and has been used to treat more than 30,000 patients.
Data Cutoff Date: 2026-02-20
Note: Adverse events are coded using MedDRA version 28.1. Multiple occurrences of the same preferred term will only be counted once for each patient.
1. Five most common TEAEs in the combination arm
Rapid, Near-Doubling and Sustained SVR35 Rates
Similar Improvement in Symptoms Relative to Ruxolitinib
Promising Signal in Overall Survival
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 on the Totality of the Data and sNDA Filing Plan
Present SENTRY results at medical meeting and submit manuscript for publication
Potential compendia inclusion in the second half of 2026
JAKi-naïve Patients
with Myelofibrosis
(n=58)
Plt ≥50 x 109/L
Selinexor 60 mg QW
(n=29)
Selinexor 40 mg QW
(n=29)
Primary Endpoint
SVR35 at week 24
Key Secondary Endpoints
Abs-TSS at week 241
Anemia response
PK/PD
Optional Add-on Medications
Week 12 if SVR <10%
Week 24 if SVR <35%
Add ruxolitinib2: if plt >50 x 109/L, and hemoglobin level is ≥ 10 g/dL
Add pacritinib: if plt <50 x 109/L1 • 4
Add momelotinib3 if plt >50 x109/L hemoglobin level is <10 g/dL
* NCT05980806
Pacritinib supply agreement with SOBI
The safety and efficacy of selinexor in myelofibrosis has not been established and has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis.
Topline data from all patients in the 60 mg cohort with at least 24 weeks of follow-up
expected in the second half of 2026
1. Evaluated in the myelofibrosis assessment form (MFSAF) 2. Ruxolitinib dose based on platelet count per prescribing information 3.In the U.S. only 4. For supply of pacritinib Plt: platelet; QW: Once weekly; SVR 35: Spleen volume reduction ≥ 35%; TSS50: Total symptom score reduction of ≥50%; PD: pharmacodynamic; PK: Pharmacokinetic
Opportunity to expand XPO1 inhibition across other MPNs1 (PV & ET) with eltanexor
Eltanexor is positioned to be our leading next generation XPO1 inhibitor in
MPNs2
1. Myeloproliferative neoplasms (MPNs) include myelofibrosis (MF), polycythemia vera (PV) and essential thrombocythemia (ET). 2. Preclinical data on file.
Disclaimer
Karyopharm Therapeutics Inc. published this content on April 16, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 16, 2026 at 11:23 UTC.