Karyopharm's Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint, Demonstrating Statistically Significant Improvement in Spleen Volume Reduction

Rhea-AI Summary

Karyopharm (Nasdaq: KPTI) reported topline Phase 3 SENTRY results in frontline myelofibrosis (n=353). The trial met its first co-primary endpoint: SVR35 50% vs 28% at Week 24 (one-sided p<0.0001) for selinexor plus ruxolitinib. The Abs-TSS symptom endpoint was not met. A promising overall survival signal (HR 0.43) was observed; safety showed higher grade 3+ TEAEs with the combination.

Positive

• SVR35 50% vs 28% at Week 24 (one-sided p<0.0001)
• Rapid spleen responses: 49% achieved SVR35 by Week 12 with combination
• Overall survival signal: hazard ratio 0.43 (95% CI [0.19,1.00]) favoring combination
• Evidence of VAF reduction: 32% ≥20% VAF reduction vs 24% at Week 24

Negative

• Did not meet second co-primary endpoint: Abs-TSS at Week 24
• Higher grade 3+ TEAEs: 70% vs 50% for combination versus control
• Treatment discontinuations: 15% vs 9% with combination
• Higher thrombocytopenia: 59% vs 43% in combination arm

News Market Reaction – KPTI

-18.32% 21.3x vol

37 alerts

-18.32% Session close to close

+40.5% Peak Tracked

-19.0% Trough Tracked

$122.17M Market Cap

21.3x Rel. Volume

In the Mar 24 session, KPTI declined 18.32%, reflecting a significant negative market reaction. Argus tracked a peak move of +40.5% during that session. Argus tracked a trough of -19.0% from its starting point during tracking. Our momentum scanner triggered 37 alerts that day, indicating elevated trading interest and price volatility. Trading volume was exceptionally heavy at 21.3x the daily average, suggesting significant selling pressure.

Data tracked by StockTitan Argus on the day of publication.

Market Context

The stock dropped -18.3% in the session following this news. A negative reaction despite meeting the...

Analysis

The stock dropped -18.3% in the session following this news. A negative reaction despite meeting the SVR35 co-primary endpoint fits KPTI’s history of volatile responses to SENTRY updates, including prior moves of -5.59% and -5.59% around clinical and funding news. The mixed profile—efficacy on spleen volume but no statistical symptom benefit—may have amplified concerns already flagged in recent 8-K disclosures about liquidity. Existing resale capacity and past capital-structure actions could also reinforce worries about future equity issuance.

Key Figures

SENTRY sample size: 353 patients (n=353) SVR35 at week 24: 50% vs 28% Early SVR35 at week 12: 49% vs 20% +5 more

8 metrics

SENTRY sample size 353 patients (n=353) Phase 3 SENTRY myelofibrosis trial, selinexor + ruxolitinib vs ruxolitinib

SVR35 at week 24 50% vs 28% Combo selinexor+ruxolitinib vs ruxolitinib alone, spleen volume reduction ≥35%

Early SVR35 at week 12 49% vs 20% Combo vs control spleen response rate at week 12

Overall survival hazard ratio HR 0.43 (95% CI 0.19–1.00), p=0.0222 OS signal selinexor+ruxolitinib vs ruxolitinib alone

Abs-TSS change week 24 9.89 vs 10.86 points Symptom score improvement combo vs control; co-primary endpoint not met

VAF ≥20% reduction 32% vs 24% (n=261) JAK2/MPL/CALR variant allele frequency reduction at week 24, combo vs control

Grade ≥3 TEAEs 70% vs 50% Rate of severe treatment-emergent adverse events, combo vs placebo+ruxolitinib

TEAEs causing discontinuation 15% vs 9% Adverse events leading to treatment discontinuation, combo vs control

Previous Clinical trial Reports

4 past events · Latest: Jan 12 (Positive)

Same Type Pattern 4 events

Date	Event	Sentiment	24h Move	Catalyst
Jan 12	Clinical & revenue update	Positive	-5.6%	Prelim 2025 revenue, cash runway into 2Q26, SENTRY Phase 3 timing.
Oct 08	Financing for trials	Positive	+2.3%	Financing transactions extending runway into 2Q26 before SENTRY data.
Sep 10	SENTRY enrollment done	Positive	-1.9%	Completion of enrollment in Phase 3 SENTRY trial with 353 patients.
Oct 31	Endpoint change SENTRY	Positive	+17.8%	Favorable change in co-primary endpoint after FDA feedback, strong Phase 1 data.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Pattern Detected

Clinical/strategic SENTRY updates have produced mixed reactions: strong gains on favorable trial design changes, but selloffs on funding/preview updates tied to the same program.

Recent Company History

Over the past 18 months, Karyopharm has repeatedly highlighted its Phase 3 SENTRY program in myelofibrosis. In Oct 2024, a favorable co-primary endpoint change and strong Phase 1 data drove a 17.81% gain. Completion of SENTRY enrollment in Sept 2025 and subsequent financing and runway extensions into 2Q 2026 saw smaller, mixed price moves. A January 2026 update on preliminary 2025 revenue and SENTRY timelines triggered a -5.59% move. Today’s topline results mark the long-anticipated efficacy readout that these prior milestones were building toward.

Key Terms

phase 3, randomized, double-blind, placebo-controlled, spleen volume reduction, absolute total symptom score (Abs-TSS), +3 more

7 terms

phase 3 medical

"topline results from its Phase 3 SENTRY trial, a randomized, double-blind..."

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

randomized, double-blind, placebo-controlled medical

"Phase 3 SENTRY trial, a randomized, double-blind, placebo-controlled trial..."

A "randomized, double-blind, placebo-controlled" process is a method used to test the effectiveness of a new treatment or intervention. Participants are randomly assigned to different groups, with one receiving the real treatment and the other a fake version, called a placebo. Neither the participants nor the researchers know who is receiving which, which helps ensure unbiased results. For investors, this rigorous approach increases confidence that the findings are accurate and not influenced by guesswork or bias.

spleen volume reduction medical

"demonstrating statistically significant improvement in spleen volume reduction of 35% or more (SVR35)..."

A measured decrease in the size of the spleen, typically assessed by imaging scans or clinical exams, used as a medical endpoint to show that a treatment is reducing organ enlargement. For investors, spleen volume reduction matters because it can be a clear sign a therapy is working, influence regulatory approval and reimbursement decisions, and affect market potential—similar to watching a swelling go down as proof that a remedy is effective.

absolute total symptom score (Abs-TSS) medical

"The mean change in absolute total symptom score (Abs-TSS) at week 24 relative to baseline..."

A composite clinical-trial measure that adds together patient ratings for multiple symptoms to produce a single numerical score reflecting overall disease severity. Investors watch this score because changes show whether a treatment meaningfully reduces symptoms — like a single thermometer reading or scorecard that summarizes many small readings — which can drive regulatory approval, prescribing use and commercial value.

hazard ratio medical

"with a hazard ratio of 0.43 (95% CI [0.19, 1.00] nominal one-sided p=0.0222)."

A hazard ratio is a way scientists compare the chance of something happening over time between two groups, like patients taking different medicines. If the ratio is high, it means one group is more likely to experience the event sooner or more often, which helps determine how effective a treatment is or how risky a situation might be.

variant allele frequency (VAF) medical

"achieved a ≥20% reduction in VAF for JAK2, MPL, and CALR compared..."

Variant allele frequency (VAF) is the proportion of DNA copies in a sample that carry a specific genetic change, expressed as a percentage or fraction. Think of checking a jar of coins and counting how many show a marked face — VAF tells you how common the marked coin is among all coins. For investors, VAF helps assess how prevalent a mutation is in a patient or product sample, which can influence the perceived effectiveness of diagnostics, targeted therapies, clinical trial results, and regulatory or commercial value.

treatment emergent adverse events (TEAEs) medical

"The five most common all-grade treatment emergent adverse events (TEAEs) in the selinexor plus ruxolitinib arm..."

Treatment-emergent adverse events (TEAEs) are any new side effects or worsening of existing health problems that begin after a person starts a drug or medical treatment during a clinical trial or real-world use. Investors watch TEAEs because they reveal a product’s safety profile and can affect regulatory approval, prescribing restrictions, market acceptance and legal risk—like warning lights that signal potential problems with a new car.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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– While Similar Symptom Improvement Was Observed Across the Two Arms Relative to Baseline, SENTRY Did Not Meet its Second Co-Primary Endpoint of Abs-TSS –

– SENTRY Demonstrated a Rapid and Near Doubling of Patients Achieving SVR35 at Week 24, versus Ruxolitinib –

– Promising Overall Survival Signal with >50% Reduction of Risk of Death versus Ruxolitinib –

– Evidence of Potential Disease Modification with More Patients Achieving ≥20% Reductions in VAF as Early as Week 24 versus Ruxolitinib –

– No New Safety Signals Identified –

– Karyopharm will Meet with the FDA to Discuss the Totality of the Data and Potential sNDA Filing –

– Conference Call Scheduled for Today at 8:00 a.m. ET –

NEWTON, Mass., March 24, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported topline results from its Phase 3 SENTRY trial, a randomized, double-blind, placebo-controlled trial of 60 mg selinexor in combination with ruxolitinib in frontline myelofibrosis (n=353). The trial met the first co-primary endpoint, demonstrating statistically significant improvement in spleen volume reduction of 35% or more (SVR35) for patients treated with the combination of selinexor plus ruxolitinib, with rapid, deep and sustained spleen volume reduction rates seen in the combination arm. The mean change in absolute total symptom score (Abs-TSS) at week 24 relative to baseline was comparable across the two arms with similar symptom improvement relative to baseline; the difference across the two arms was not statistically significant. Importantly, the topline results suggest a promising signal in overall survival (OS) for the combination arm.

• Spleen Volume: 50% of patients who received the combination of selinexor plus ruxolitinib achieved a statistically significant improvement in SVR35 at week 24 compared to 28% of patients who received ruxolitinib alone (one-sided p<0.0001). Patients on the combination achieved rapid spleen reduction with 49% already achieving SVR35 at week 12 compared to 20% who received ruxolitinib alone. Spleen volume reduction was sustained, with 47% of patients on the combination achieving SVR35 at week 36 compared to 23% who received ruxolitinib alone.
  
  
• Symptoms: Similar symptom improvement from baseline was observed in patients who received the combination of selinexor plus ruxolitinib compared to ruxolitinib alone as measured by Abs-TSS at week 24. Patients who received the combination reported a 9.89 point improvement in Abs-TSS compared to a 10.86 point improvement in patients who received ruxolitinib alone.
  
  
• Overall Survival: Promising OS signal was observed in patients who received the combination of selinexor plus ruxolitinib compared to ruxolitinib alone with a hazard ratio of 0.43 (95% CI [0.19, 1.00] nominal one-sided p=0.0222). The Company intends to continue to follow OS to maturity to further evaluate this signal.
  
  
• Overall Survival Associated with SVR35: Post-hoc landmark analyses at weeks 12 and 24 suggest SVR35 may predict overall survival.
  
  
• Variant Allele Frequency (VAF) Reduction: Evidence of potential disease modification from a pre-specified exploratory endpoint was observed at week 24 from baseline in the combination arm as 32% of patients who received the combination achieved a ≥20% reduction in VAF for JAK2, MPL, and CALR compared to 24% of patients who received ruxolitinib alone (n=261).
  
  
• Other Secondary and Exploratory Endpoints: Across other secondary and exploratory endpoints of progression-free survival, hemoglobin stabilization, and bone marrow fibrosis improvement, no meaningful difference was observed between the trial arms as of the data cut-off of February 20, 2026. The Company intends to further evaluate these endpoints as they mature.  

Patients were randomized 2:1 to 60 mg of selinexor once weekly plus ruxolitinib or placebo plus ruxolitinib. The ruxolitinib dose was determined based on the patients' baseline platelet count per the drug's prescribing information. All data presented are as of the data cut-off of February 20, 2026.

"The results from SENTRY are an important development for patients as the combination of selinexor plus ruxolitinib meaningfully improved spleen response and we observed a promising signal in overall survival. Reducing spleen volume remains one of the most important treatment goals in myelofibrosis since achieving SVR35 is associated with improvement in overall survival," said Dr. John Mascarenhas, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. "While the symptom endpoint did not reach statistical significance, patients treated in both arms achieved similar symptom improvement relative to baseline. Importantly, while JAK inhibitors have been the backbone of therapy, continued progress requires new therapies that target additional biological pathways. Inhibition of XPO1 represents a differentiated mechanism that has the potential to address these pathways and evolve treatment beyond JAK inhibition alone."

"For patients with myelofibrosis, improvements in spleen and symptoms are expected outcomes from JAK inhibitors such as ruxolitinib. The SENTRY topline results suggest that the combination of selinexor and ruxolitinib delivers superior spleen reduction, which may predict overall survival, while offering similar symptom improvement, and may offer an important advance for our patients," said Dr. Claire Harrison, Professor of Myeloproliferative Neoplasms and Deputy Chief Medical Officer of Research, Data, and Analytics at Guy's and St. Thomas' NHS Foundation Trust in the United Kingdom.

"Selinexor's differentiated mechanism provides a complementary approach to JAK inhibition and highlights the importance of targeting additional biological pathways beyond JAK signaling to further advance outcomes for patients with myelofibrosis. I am encouraged by the speed and magnitude of spleen response, and the promising overall survival signal and evidence of potential disease modification. In totality, these data underscore selinexor's potential to meaningfully improve clinical outcomes for patients with myelofibrosis," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research of Karyopharm. "On behalf of Karyopharm, I would like to thank the patients, families, caregivers, investigators, and clinical trial team who participated in this trial. We are excited to share our results with regulatory authorities, key opinion leaders and patient advocacy organizations."

"The myelofibrosis community is waiting for new treatment options that can build upon the benefit of JAK inhibitors. Improving overall survival is the ultimate goal for people living with myelofibrosis and I am incredibly encouraged by these results," said Kapila Viges, Chief Executive Officer of the MPN Research Foundation. "These results are an exciting development for the myelofibrosis community."

Safety and Tolerability

The combination demonstrated a manageable safety and tolerability profile consistent with the known profile of selinexor and ruxolitinib individually. No new safety signals were observed.

The five most common all-grade treatment emergent adverse events (TEAEs) in the selinexor plus ruxolitinib arm were thrombocytopenia (selinexor plus ruxolitinib arm: 59%; placebo plus ruxolitinib arm: 43%), anemia (57%; 58%), nausea (57%; 17%), constipation (32%; 36%) and neutropenia (27%; 9%) (n=234; n=116). The rate of grade 3+ TEAEs was 70% in the selinexor plus ruxolitinib arm compared to 50% in the placebo plus ruxolitinib arm. The rate of TEAEs leading to treatment discontinuation was 15% in the selinexor plus ruxolitinib arm and 9% in the placebo plus ruxolitinib arm. The rate of confirmed leukemic transformations was the same across both arms of the trial at 1.7%.  

Next Steps

The Company will be meeting with the U.S. Food and Drug Administration (FDA) to discuss the totality of the data from the SENTRY trial and its supplemental new drug application (sNDA) filing plan.  

The Company plans to share additional data from the Phase 3 SENTRY trial at an upcoming medical meeting and expects to submit a manuscript to a peer-reviewed medical journal. The Company believes that potential inclusion in relevant compendia could occur in the second half of 2026.

Conference Call Information

Karyopharm will host a conference call today, March 24, 2026, at 8:00 a.m. Eastern Time, to discuss the results of its Phase 3 SENTRY trial in myelofibrosis. To access the conference call, please dial (800) 836-8184 (local) or (646) 357-8785 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company's website. An archived webcast will be available on the Company's website approximately two hours after the event.

About the Phase 3 SENTRY Trial

SENTRY (XPORT-MF-034; NCT04562389) is a Phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 10⁹/L. Patients were randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline.

About Myelofibrosis

Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union¹. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib.  

1. Clarivate/DRG (2023)

About XPOVIO® (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor compound for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in adult patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO® (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO®/NEXPOVIO® is marketed in these respective ex-U.S. territories by Karyopharm's partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in myelofibrosis and endometrial cancer.

For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: medicalinformation@karyopharm.com

XPOVIO^® (selinexor) is a prescription medicine approved:

• In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
  
  
• In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti‐CD38 monoclonal antibody (Xd).
  
  
• For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

• Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
• Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors.
• Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
• Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
• Serious Infection: Monitor for infection and treat promptly.
• Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
• Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
• Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.

Adverse Reactions

• The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
  
  
• The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
  
  
• The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.

Use In Specific Populations
     Lactation: Advise not to breastfeed.

     For additional product information, including full prescribing information, please visit www.XPOVIO.com.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

About Karyopharm Therapeutics

Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company whose dedication to pioneering novel cancer therapies is fueled by a belief in the extraordinary strength and courage of patients with cancer. Since its founding, Karyopharm has been an industry leader in oral compounds that address nuclear export dysregulation, a fundamental mechanism of oncogenesis. Karyopharm's lead compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications. It has also received regulatory approvals in various indications in 50 ex-U.S. territories and countries, including the European Union, the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline targeting indications in multiple high unmet need cancers, including in multiple myeloma, endometrial cancer, myelofibrosis, and diffuse large B-cell lymphoma (DLBCL). For more information about our people, science and pipeline, please visit www.karyopharm.com, and follow us on LinkedIn and on X at @Karyopharm.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, diffuse large B-cell lymphoma and other diseases; expectations with respect to the clinical development plans, regulatory discussions and potential regulatory submissions for selinexor; and expectations regarding the timing, presentation and publication of additional data from the Phase 3 SENTRY trial. 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 press release 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 trials 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 press release 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.

XPOVIO^® and NEXPOVIO^® are registered trademarks of Karyopharm Therapeutics Inc.

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SOURCE Karyopharm Therapeutics Inc.

FAQ

What were the key Phase 3 SENTRY results for Karyopharm (KPTI) announced March 24, 2026?

The combination met the spleen co-primary: SVR35 50% vs 28% at Week 24 with one-sided p<0.0001. According to the company, Abs-TSS was comparable across arms and did not reach statistical significance, while a promising overall survival signal was observed (HR 0.43).

How did selinexor plus ruxolitinib affect overall survival in the SENTRY trial (KPTI)?

A promising overall survival signal favored the combination with a hazard ratio of 0.43. According to the company, the result is preliminary and OS will continue to be followed to maturity to further evaluate this signal.

Did the SENTRY trial (KPTI) meet the symptom endpoint Abs-TSS at Week 24?

No, the Abs-TSS co-primary endpoint was not met; symptom improvements were similar across arms. According to the company, patients in both arms showed comparable symptom improvement versus baseline, with no statistically significant difference between arms at Week 24.

What safety differences did Karyopharm report for selinexor plus ruxolitinib in SENTRY?

The combination had higher toxicity: grade 3+ TEAEs 70% vs 50% and higher discontinuations. According to the company, common TEAEs included thrombocytopenia, anemia, nausea, constipation, and neutropenia, with a manageable tolerability profile and no new safety signals.

How quickly did patients achieve spleen reductions in the SENTRY study for KPTI?

Spleen reductions were rapid: 49% achieved SVR35 by Week 12 on the combination versus 20% with ruxolitinib alone. According to the company, spleen responses were deep and sustained through Week 36, supporting the primary spleen endpoint result.

What are Karyopharm's next steps after the SENTRY Phase 3 results (KPTI)?

Karyopharm plans to meet with the FDA to discuss the totality of SENTRY data and an sNDA filing path. According to the company, additional data will be presented at a medical meeting, a manuscript will be submitted, and potential compendia inclusion could occur in H2 2026.