SENTRY myelofibrosis data and $30M private placement reshape Karyopharm (NASDAQ: KPTI)
Rhea-AI Filing Summary
Karyopharm Therapeutics entered a private placement with RA Capital, selling 1,030,354 common shares, 3,391,164 pre-funded warrants, and 4,421,518 common warrants, for about $30 million in gross proceeds, plus about $44 million if all warrants are exercised. In March 2026 it also sold 1,100,844 shares via its at-the-market program for about $9.6 million net, and had 19,618,032 shares outstanding as of March 23, 2026. Closing the private placement will satisfy the capital-raise trigger for its amended credit and forbearance agreements.
The Phase 3 SENTRY myelofibrosis trial met the spleen-volume co-primary endpoint, with 50% of patients on selinexor plus ruxolitinib achieving SVR35 at week 24 versus 28% on ruxolitinib alone, but did not show a statistically significant symptom-score benefit. A nominally significant overall-survival signal was reported with a hazard ratio of 0.43. Safety showed more grade 3+ adverse events (70% vs 50%) and higher discontinuations (15% vs 9%). Karyopharm will seek FDA feedback on a supplemental NDA. The company will voluntarily withdraw the accelerated approval for the DLBCL indication of XPOVIO due to feasibility of completing the confirmatory trial, noting minimal revenue from that use.
Positive
- None.
Negative
- None.
Insights
Mixed but meaningful: stronger myelofibrosis data, new capital, and a focused pipeline.
The SENTRY Phase 3 readout is clinically important. Selinexor plus ruxolitinib nearly doubled spleen responses (SVR35 50% vs 28%) and showed a nominal overall-survival hazard ratio of 0.43, but failed to improve symptom scores versus ruxolitinib alone. Safety was consistent with mechanism yet had higher grade 3+ adverse events and discontinuations.
On the finance side, the $30 million private placement with RA Capital, plus up to about $44 million on warrant exercise and the $9.6 million from recent ATM sales, strengthens near-term liquidity and triggers effectiveness of the amended credit and forbearance agreements. Management still cites substantial doubt about continuing as a going concern, and expects current funding to last into late Q3 2026, so longer-term capital needs remain.
Strategically, withdrawing the DLBCL accelerated approval removes an indication that generates immaterial revenue but allows Karyopharm to stop further clinical spending there and concentrate on myelofibrosis, endometrial cancer and multiple myeloma. Upcoming milestones include topline data for the Phase 2 SENTRY-2 cohort in the second half of 2026 and for the XPORT-EC-042 endometrial cancer trial in mid-2026, which will further shape selinexor’s future role.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
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FORM
CURRENT REPORT
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| Item 1.01 | Entry into a Material Definitive Agreement. |
Securities Purchase Agreement
On March 24, 2026, Karyopharm Therapeutics Inc. (the “Company”) entered into a Securities Purchase Agreement (the “Purchase Agreement”) with RA Capital Management (the “Investor”), pursuant to which the Company agreed to issue and sell (i) 1,030,354 shares (the “Shares”) of its common stock, par value $0.0001 per share (“Common Stock”), at a purchase price of $6.785 per share and, in lieu of Common Stock, pre-funded warrants to purchase up to 3,391,164 shares of Common Stock (the “Pre-Funded Warrants”) at a purchase price of $6.7849 per pre-funded warrant, and (ii) accompanying warrants to purchase 4,421,518 shares of Common Stock with an exercise price of $10.00 per share (the “Common Stock Warrants”) to the Investor in a private placement (collectively, the “Private Placement”).
The Private Placement is expected to result in gross proceeds of approximately $30 million at closing to the Company, before placement agent fees and offering expenses. The Company will receive an additional approximately $44 million of gross proceeds if the accompanying Common Stock Warrants are exercised in full. The Company intends to use the proceeds from the Private Placement for general corporate purposes, including to support the Company’s ongoing and planned clinical trial activities. The closing of the Private Placement is subject to customary closing conditions and is expected to occur on or about March 26, 2026.
Jefferies LLC and Piper Sandler & Co. acted as placement agents for the Private Placement.
The Securities Purchase Agreement provides that, from the date of the Securities Purchase Agreement until the business day immediately following the effective date of the registration statement filed pursuant to the Registration Rights Agreement (as defined herein), the Company may not issue shares of Common Stock or common stock equivalents, or file with the Securities and Exchange Commission (the “SEC”) a registration statement under the Securities Act of 1933, as amended (the “Securities Act”) relating to any shares of Common Stock or common stock equivalents; provided that such restrictions do not apply to the filing of a primary shelf registration statement on Form S-3 to replace the Company’s existing primary shelf registration statement on Form S-3 upon the expiration or termination thereof covering substantially the same categories of securities and transaction types as the existing shelf registration statement, or the issuance and sale of shares of Common Stock pursuant to the Open Market Sale AgreementSM, by and between the Company and Jefferies LLC, dated February 17, 2023 (the “Sale Agreement”).
The Securities Purchase Agreement contains customary representations, warranties and agreements by the Company, customary conditions to closing, indemnification obligations of the Company, other obligations of the parties and termination provisions. The representations, warranties and covenants contained in the Securities Purchase Agreement were made only for purposes of such agreement and as of specific dates, were solely for the benefit of the parties to such agreement, and may be subject to limitations agreed upon by the contracting parties. The above description of the Securities Purchase Agreement is a summary only and is qualified in its entirety by reference to the Securities Purchase Agreement, a copy of which is filed as Exhibit 10.1 to the Current Report on Form 8-K and is incorporated by reference herein.
Registration Rights Agreement
In connection with the Private Placement, the Company will enter into a registration rights agreement (the “Registration Rights Agreement”) with the Investor, pursuant to which the Company will agree to file a registration statement with the SEC covering the resale of the Shares and the shares of common stock issuable upon exercise of the Pre-Funded Warrants and the Common Stock Warrants (collectively, the “Registrable Securities”) as promptly as reasonably practicable, and in any event no later than 45 days after the closing of the Private Placement (the “Filing Deadline”). The Company will agree to use reasonable best efforts to cause the registration statement to be declared effective as soon as practicable, and in any event no later than the earlier of (i) the 90th calendar day following the initial filing date of the registration statement, if the SEC notifies the Company that it will review the registration statement, and (ii) the fifth business day after the date the Company is notified by the SEC that the registration statement will not be reviewed or will not be subject to further review. The Company will agree to keep the registration statement effective until the earlier of (a) the date all Registrable Securities covered by the registration statement have been sold and (b) the date the Registrable Securities may be resold without registration and without regard to any volume or manner-of-sale limitations under Rule 144 promulgated under the Securities Act (“Rule 144”), without the requirement for the Company to be in compliance with the current public information requirement under Rule 144.
The Company will agree to pay the expenses of registering the Registrable Securities, other than underwriting discounts and commissions and similar selling expenses. The Registration Rights Agreement will also provide for customary indemnification rights and will require the Company to pay liquidated damages in certain circumstances if it fails to meet specified filing or effectiveness deadlines or if the registration statement is otherwise unavailable for resales, in each case as set forth in the Registration Rights Agreement.
The Company will grant the Investor customary indemnification rights in connection with the registration statement, including for liabilities arising under the Securities Act. The Investor will also grant the Company customary indemnification rights in connection with the registration statement.
The above description of the Registration Rights Agreement is a summary only and is qualified in its entirety by reference to the Form of Registration Rights Agreement, a copy of which is filed as Exhibit 10.2 to the Current Report on Form 8-K and is incorporated by reference herein.
Pre-Funded Warrants
The exercise price of the Pre-Funded Warrants will be $0.0001 per share and the Pre-Funded Warrants will be immediately exercisable and will not expire. Under the terms of the Pre-Funded Warrants, the Company may not effect the exercise of any Pre-Funded Warrants, and a holder will not be entitled to exercise any portion of any Pre-Funded Warrants, which, upon giving effect to such exercise, would cause a holder (together with its attribution parties) to own more than 9.99% of the number of shares of the common stock outstanding immediately after giving effect to such exercise, as such percentage ownership is determined in accordance with the terms of the Pre-Funded Warrants. However, any holder may increase or decrease such percentage to any other percentage not in excess of 19.99%, provided that any increase in such percentage shall not be effective until 61 days after such notice is delivered to the Company.
The above description of the Pre-Funded Warrants is a summary only and is qualified in its entirety by reference to the Form of Pre-Funded Warrant, a copy of which is filed as Exhibit 4.1 to the Current Report on Form 8-K and is incorporated by reference herein.
Warrants
The exercise price of the Common Stock Warrants will be $10.00 per share. The exercise price of the Common Stock Warrants may only be paid in cash; provided, however, that if a registration statement covering the resale of shares of common stock issuable upon exercise of any Common Stock Warrant is not in effect at the time such Common Stock Warrant is exercised, the holder of such Common Stock Warrants may elect to effect a cashless exercise of such Common Stock Warrants.
The Common Stock Warrants will be immediately exercisable and will expire 30 days following the public announcement by the Company of the topline results from the Phase 3 XPORT-EC-042 clinical trial of selinexor in patients with endometrial cancer.
Under the terms of the Common Stock Warrants, the Company may not effect the exercise of any Common Stock Warrant, and a holder will not be entitled to exercise any portion of any Common Stock Warrant, which, upon giving effect to such exercise, would cause a holder (together with its attribution parties) to own more than 9.99% of the number of shares of the common stock outstanding immediately after giving effect to such exercise, as such percentage ownership is determined in accordance with the terms of the Common Stock Warrants. However, any holder may increase or decrease such percentage to any other percentage not in excess of 19.99%, provided that any increase in such percentage shall not be effective until 61 days after such notice is delivered to the Company.
The above description of the Common Stock Warrants is a summary only and is qualified in its entirety by reference to the Form of Common Stock Warrant, a copy of which is filed as Exhibit 4.2 to the Current Report on Form 8-K and is incorporated by reference herein.
| Item 3.02 | Unregistered Sales of Equity Securities. |
The information set forth under Item 1.01 of this Current Report on Form 8-K is incorporated herein by reference.
The securities described above are being issued in the Private Placement in reliance on the exemption from registration provided by Section 4(a)(2) of the Securities Act. The Company is relying on this exemption from registration based in part on representations made by the Investor. The securities described herein have not been registered under the Securities Act or any state securities laws, and such securities may not be offered or sold in the United States absent registration with the SEC or an applicable exemption from the registration requirements. The sale of securities described herein will not involve a public offering and will be made without general solicitation or general advertising. The purchaser of the securities described
herein represented, among other things, that it is an accredited investor, as such term is defined in Rule 501(a) of Regulation D under the Securities Act, and that it is acquiring such securities for investment purposes only and not with a view to any resale, distribution or other disposition of the Shares, the Pre-Funded Warrants and the Common Stock Warrants in violation of the United States federal securities laws.
Neither this Current Report on Form 8-K nor any exhibit attached hereto is an offer to sell or the solicitation of an offer to buy any securities of the Company.
| Item 7.01 | Regulation FD Disclosure. |
SENTRY Trial Topline Data
On March 24, 2026, the Company issued a press release announcing topline results from its pivotal 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 “SENTRY trial”). A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
The Company intends to host a conference call and live webcast to discuss the results on March 24, 2026 at 8:00 a.m. Eastern Time and has made available the slide presentation to accompany the call, furnished herewith as Exhibit 99.2 to this Current Report on Form 8-K.
Private Placement
On March 24, 2026, the Company also issued a press release announcing the Private Placement. A copy of the press release is furnished as Exhibit 99.3 to this Current Report on Form 8-K.
The information in this Item 7.01 (including Exhibits 99.1, 99.2 and 99.3) is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such a filing.
| Item 8.01 | Other Events. |
SENTRY Trial Topline Data
On March 24, 2026, the Company announced topline results from its SENTRY trial in which 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 date of February 20, 2026.
The SENTRY 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. 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.
Spleen Volume (Co-Primary Endpoint): 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% 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. The difference across the two arms was not statistically significant.
Symptoms (Co-Primary Endpoint): 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 (Secondary Endpoint): Promising overall survival (“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 (Pre-Specified Exploratory Endpoint): 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 greater than or equal to 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.
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%.
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 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.
SENTRY-2 Trial Update
Topline data from all patients in the 60 mg cohort of the Phase 2 SENTRY-2 trial with at least 24 weeks of follow-up is expected in the second half of 2026.
Endometrial Cancer Update
Topline data from the event-driven, Phase 3 XPORT-EC-042 trial is expected in mid-2026.
Diffuse Large B-Cell Lymphoma Update
In March 2026, the Company met with the FDA regarding the Accelerated Approval of the Diffuse Large B-Cell Lymphoma (“DLBCL”) indication of XPOVIO® (selinexor) which was granted on June 22, 2020 for the treatment of adult patients with relapsed or refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. During the meeting, the FDA 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, especially considering the evolving treatment landscape rendering the confirmatory trial study design impractical. As a result, the Company will cease ongoing and any further clinical development and related operational expenses in this indication. This withdrawal is not due to safety concerns with the DLBCL indication and does not affect the regulatory approval of any other indications for XPOVIO. The Company does not promote XPOVIO for this indication and generates immaterial revenue from DLBCL sales.
ATM
In March 2026, the Company issued and sold an aggregate of 1,100,844 shares of Common Stock under its Sale Agreement for total proceeds, net of sales commissions, of approximately $9.6 million. As of March 23, 2026, the Company had 19,618,032 shares of Common Stock outstanding.
Satisfaction of Capital Raise Trigger Under Second Amendment to Credit and Guaranty Agreement and the Forbearance Agreement
Upon receipt of the proceeds from the Private Placement on the closing date, the Company will have satisfied the capital raise trigger condition to the effectiveness of (i) the Second Amendment to Credit and Guaranty Agreement, dated February 27, 2026 (the “Amendment”), with the lenders party thereto and Wilmington Savings Fund Society, FSB, as administrative agent and collateral agent, which amended the Company’s Credit and Guaranty Agreement, dated May 8, 2024 (as previously amended, the “Credit Agreement”) and (ii) the Forbearance Agreement, dated February 27, 2026 (the “Forbearance Agreement”), with (i) 100% of the lenders under the Credit Agreement, (ii) holders representing 100% of the outstanding principal amount of the Company’s 9.00% Convertible Senior Notes due 2028, (iii) holders representing 100% of the outstanding principal amount of the Company’s 9.00% Convertible Senior Notes due 2029, and (iv) the investor representative acting at the direction of the investors under the Company’s revenue interest financing agreement, and each of the Amendment and the Forbearance Agreement will be effective.
The terms of the Amendment and the Forbearance Agreement were disclosed in a Current Report on Form 8-K filed by the Company on February 27, 2026.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 4.1 | Form of Pre-Funded Warrant to Purchase Common Stock | |
| 4.2 | Form of Warrant to Purchase Common Stock | |
| 10.1* | Securities Purchase Agreement, dated March 24, 2026, by and between the Company and the Investor | |
| 10.2 | Form of Registration Rights Agreement | |
| 99.1 | Press Release issued by Karyopharm Therapeutics Inc. on March 24, 2026 | |
| 99.2 | Corporate Presentation issued by Karyopharm Therapeutics Inc. on March 24, 2026 | |
| 99.3 | Press Release issued by Karyopharm Therapeutics Inc. on March 24, 2026 | |
| 104 | Cover Page Interactive Data File (formatted as Inline XBRL) | |
| * | Certain exhibits have been omitted pursuant to Item 601(a)(5) of Regulation S-K. |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| KARYOPHARM THERAPEUTICS INC. | ||||||
| Date: March 24, 2026 | By: | /s/ Michael Mano | ||||
| Michael Mano | ||||||
| Executive Vice President, Chief Legal Officer and Secretary | ||||||
Exhibit 99.1
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BELIEVERS IN THE EXTRAORDINARY |
Karyopharm’s Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint, Demonstrating Statistically Significant Improvement in Spleen Volume Reduction
– 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 – 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. |
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| • | 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.”
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“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.
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BELIEVERS IN THE EXTRAORDINARY |
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. |
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BELIEVERS IN THE EXTRAORDINARY |
| • | 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.
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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;
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BELIEVERS IN THE EXTRAORDINARY |
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.
CONTACTS:
Investors:
Brendan Strong
Senior Vice President, Investor Relations
617.762.2661
brendan.strong@karyopharm.com
Media:
Mary Ann Ondish
Head of Corporate Communications
914.552.4625
Maryann.ondish@karyopharm.com
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Exhibit 99.2 Phase 3 SENTRY Topline Results March 24, 2026
On Today’s Call Welcome Brendan Strong, SVP, Investor Relations Opening Remarks Richard Paulson, President and Chief Executive Officer Phase 3 SENTRY Topline Results Dr. Reshma Rangwala, Chief Medical Officer and Head of Research Myelofibrosis Treatment Landscape Dr. John Mascarenhas, Principal Investigator of Phase 3 SENTRY Trial; 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 Summary Richard Paulson, President and Chief Executive Officer Q&A Session 2 ©2026 KARYOPHARM THERAPEUTICS INC.
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 beliefs about 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 and potential regulatory submissions for selinexor; the market opportunity and annual peak revenue opportunities 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 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 www.karyopharm.com, particularly the information in the section entitled “Investors,” as a source of information about Karyopharm. References to www.karyopharm.com in this presentation are not intended to, nor shall they be deemed to, incorporate information on 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 drugs 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. 3 ©2026 KARYOPHARM THERAPEUTICS INC.
OPENING REMARKS Richard Paulson President and Chief Executive Officer ©2026 KARYOPHARM THERAPEUTICS INC.
Encouraging Profile Observed with the Differentiated Mechanism of XPO1 Inhibition and Ruxolitinib with Potential to Improve Outcomes for Patients Co-Primary Endpoint Co-Primary Endpoint Secondary Endpoint Statistically Significant Not Statistically Significant Nominally Significant Promising Signal of Rapid, Near-Doubling Similar Improvement Overall Survival and Sustained SVR35 in Symptoms Rates Compared to Compared to Compared to Ruxolitinib Ruxolitinib 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. 5 ©2026 KARYOPHARM THERAPEUTICS INC.
PHASE 3 SENTRY TOPLINE RESULTS Reshma Rangwala, MD, PhD Chief Medical Officer and Head of Research ©2026 KARYOPHARM THERAPEUTICS INC.
XPO1 Inhibition is a Multifaceted Approach to Inhibiting the Drivers of 1-9 Myelofibrosis SEL ↓ Clonal cell division XPO-1 ↓ Splenomegaly Inflammatory c-myc cytokine / chemokine ↓ Variant Allele Frequency c-myc (VAF) Oncogene XPO-1 IκBα Oncogene mRNA ↓ NFκB activity ↓ Cytopenias, fibrosis, SEL Tumor suppressor protein constitutional symptoms IκBα IκBα JAK-STAT IL-6 JAK2 signaling SEL Selinexor JAKi ↑ Apoptosis JAKi JAK inhibitor ↓ Variant Allele Frequency (VAF) XPO-1 p53 p53 SEL NUCLEUS 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. 7 ©2026 KARYOPHARM THERAPEUTICS INC.
* Phase 3 SENTRY Trial (XPORT-MF-034 ) of Selinexor in Combination with Ruxolitinib in JAKi-Naïve Myelofibrosis a Ruxolitinib BID + Primary Endpoints Selinexor 60 mg QW JAKi-naïve Patients (tested sequentially) (28-day cycle) with Myelofibrosis R c SVR35 week 24 2:1 (N=353) + a Ruxolitinib BID + Abs-TSS 9 Plt >100 x 10 /L b,c,d Placebo week 24 *NCT04562389 Select Secondary and e Exploratory Endpoints Randomization stratified by: • Progression free survival • Dynamic International Prognostic Scoring System (DIPSS) risk category intermediate -1 • Overall survival vs. intermediate -2 or high-risk • Hemoglobin stabilization 3 3 • Spleen volume <1800 cm vs. >1800 cm by MRI/CT scan • Variant allele frequency (VAF) 9 9 reduction • Baseline platelet counts 100-200 x 10 / L vs. >200 x 10 /L • Bone marrow fibrosis improvement • Changes in cytokine levels 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% 8 ©2026 KARYOPHARM THERAPEUTICS INC.
Selinexor plus Ruxolitinib Resulted in Superior SVR35 Rates at Week 24 Selinexor + Placebo + Ruxolitinib Ruxolitinib (N = 235) (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) 21.82 Difference in SVR35 at Week 24 (%) Superior SVR35 at week 24 (Selinexor vs. Placebo) (11.50, 32.14) 95% CI of 50%, a near doubling compared to 28% with Cochran-Mantel-Haenszel Test (Selinexor vs. Placebo) ruxolitinib monotherapy Odds Ratio (95% CI) 2.58 (1.60, 4.17) (p<0.0001) 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. 9 ©2026 KARYOPHARM THERAPEUTICS INC.
Rapid and Sustained Improvement in SVR35 Rates Observed with the Combination Relative to Ruxolitinib Alone Selinexor + Placebo + Ruxolitinib 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 Discontinued Prior to Week 36 49% compared to 20% with SVR35 at Week 36, n (%) [1] 97 (46.9) 23 (23.0) ruxolitinib monotherapy SVR35 at Any Timepoint, n (%) 159 (67.7) 53 (44.9) Exact 95% CI (61.3, 73.6) (35.7, 54.3) Sustained SVR35 at week 36 Cochran-Mantel-Haenszel Test of 47% compared to 23% with (Selinexor vs. Placebo) Odds Ratio (95% CI) 2.59 (1.64, 4.10) ruxolitinib monotherapy Nominal One Sided P-value <.0001 Data Cutoff Date: 2026-02-20 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 Selinexor has not been approved by the U.S. FDA or 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. any other regulatory authority for use in myelofibrosis. [1] Denominator is the number of patients who completed the spleen assessment or discontinued the study prior to the specific timepoint. 10 ©2026 KARYOPHARM THERAPEUTICS INC.
Rapid, Deep and Sustained Spleen Reduction Observed with the Combination Relative to Ruxolitinib Alone 10 0 -10 -20 -30 -40 -50 -60 -70 Seli Sene linxo exr o+ r + R R ux ux oli olt itiini nib b P Plla ac ce eb boo ++ R R uux xooli litin tiinib b -80 235 118 199 102 186 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 11 ©2026 KARYOPHARM THERAPEUTICS INC. Mean(+/- SD)
Symptom Benefit at Week 24 was Comparable Across the Two Arms with Similar Symptom Improvement Relative to Baseline Selinexor + Placebo + Ruxolitinib Ruxolitinib (N = 235) (N = 118) Baseline Symptom Improvement 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 Similar levels of absolute TSS improvement from Week 24 Adjusted Absolute Mean Change -9.89 -10.86 baseline in the selinexor from Baseline (95% CI) (-11.19, -8.59) (-12.58, -9.14) Adjusted Mean Difference 0.97 plus ruxolitinib arm (Selinexor vs. Placebo) (95% CI) (-1.07, 3.02) compared to ruxolitinib One-sided P-value 0.8246 Data Cutoff Date: 2026-02-20 CI=Confidence Interval; TSS=Total Symptom Score These differences were not statistically significant 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- Selinexor has not been approved by the U.S. FDA or effects model for repeated measures (MMRM) adjusted for randomization stratification factors, sex and baseline TSS. any other regulatory authority for use in myelofibrosis. Note: n is the number of patients with TSS available. 12 ©2026 KARYOPHARM THERAPEUTICS INC.
Promising Overall Survival Signal was Observed with a >50% Reduction in Risk of Death The Company intends to continue to follow OS to maturity to further evaluate this signal Selinexor + Placebo + Ruxolitinib Ruxolitinib Overall Survival (OS) is a pre- (N = 235) (N = 118) Patients with Events, n 11 of 235 12 of 118 specified secondary endpoint Percentage (%) 4.7 10.2 Hazard ratio of 0.43 and a nominal Median OS Follow-up Time (Months) [1] 11.56 12.58 p-value of 0.0222 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- Post-hoc landmark analyses at 0.0222 rank) weeks 12 and 24 suggest Data Cutoff Date: 2026-02-20 SVR35 may predict CI=Confidence Interval Note: Overall Survival (OS) is defined as the duration from date of randomization to date of death due to any cause. overall survival [1] Based on reverse Kaplan-Meier method by swapping the censoring status. [2] Stratified by the randomization stratification factors. [3] 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. 13 ©2026 KARYOPHARM THERAPEUTICS INC.
Variant Allele Frequency (VAF) Reduction in JAK2, CALR and MPL Driver 1-3 Mutations is Evidence of Potential Disease Modification 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% 24% VS 4 Selinexor + Ruxolitinib Ruxolitinib (n=92 ) 4 Combination (n=169 ) 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 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 14 ©2026 KARYOPHARM THERAPEUTICS INC.
Manageable Safety and Tolerability Profile Selinexor + Placebo + Ruxolitinib Ruxolitinib (N = 234) (N = 116) n (%) n (%) Safety and tolerability is consistent 1 All Grade TEAEs with the known profile of selinexor Thrombocytopenia 139 (59.4) 50 (43.1) Anaemia 134 (57.3) 67 (57.8) and ruxolitinib individually Nausea 134 (57.3) 20 (17.2) Constipation 74 (31.6) 42 (36.2) Neutropenia 63 (26.9) 10 (8.6) Grade 3+ TEAEs 164 (70.1) 58 (50.0) TEAEs Leading to Study Treatment 34 (14.5) 10 (8.6) Discontinuation No new safety signals identified 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 Selinexor has not been approved by the U.S. FDA or counted once for each patient. any other regulatory authority for use in myelofibrosis. 1. Five most common TEAEs in the combination arm 15 ©2026 KARYOPHARM THERAPEUTICS INC.
Encouraging Profile Observed with the Differentiated Mechanism of XPO1 Inhibition and Ruxolitinib with Potential to Improve Outcomes for Patients 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 Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. 16 ©2026 KARYOPHARM THERAPEUTICS INC.
TREATMENT LANDSCAPE John Mascarenhas, M.D. Principal Investigator of Phase 3 SENTRY trial; 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 The views expressed today by Dr. Mascarenhas are solely his views and are not necessarily shared by Karyopharm Therapeutics Inc. ©2026 KARYOPHARM THERAPEUTICS INC.
The SENTRY Results Matter in Myelofibrosis Given the Limited Treatment Options and Poor Prognosis Opportunity to Improve Outcomes Four Hallmarks of Myelofibrosis 1 Low rates of SVR35 Enlarged 5 Spleen No novel mechanisms beyond JAK inhibitors Constitutional Abnormal Blood 2,6,7 3 Symptoms Cell Production Median survival of patients with intermediate-to-high risk 4,8 myelofibrosis is 4 to 5 years Bone Marrow 3 Fibrosis Minimal evidence of disease 9 modification 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. 18 ©2026 KARYOPHARM THERAPEUTICS INC.
Established Data from Other Trials Suggest Achieving and Maintaining Spleen Response Positively Impacts Overall Survival Coltro et. al Cancer Medicine 2023 19 ©2026 KARYOPHARM THERAPEUTICS INC.
NCCN Myelofibrosis Management and Treatment Guidelines Higher-Risk MF Lower-Risk MF 9 9 Asymptomatic Symptomatic Anemia PLT < 50x10 /L PLT ≥ 50x10 /L Based on spleen and Not transplant Not transplant • Clinical trial symptoms candidate or not Transplant candidate candidate or not • Observation • Clinical trial • Clinical trial feasible feasible • Ruxolitinib • Momelotinib • Peginterferon • Ruxolitinib alfa-2a • Luspatercept • Hydroxyurea • Danazol • Pacritinib • ESA • Clinical Trial • Clinical trial • Momelotinib • Lenalidomide/pred Allogenic HCT • Ruxolitinib • Pacritinib nisone • Fedratinib • Momelotinib • Pacritinib • Pacritinib • JAKi combination • Momelotinib Higher-risk MF typically has Lower-risk MF typically lacks or has minimal signs and several signs and symptoms symptoms and a longer median survival and a shorter median survival NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 1.2026. Accessed March 13, 2026. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf 20 ©2026 KARYOPHARM THERAPEUTICS INC.
SUMMARY Richard Paulson President and Chief Executive Officer ©2026 KARYOPHARM THERAPEUTICS INC.
Deeply Committed to Advancing the Development of Selinexor as a Potential Therapy in Myelofibrosis SENTRY Supports High Unmet Need Engage with FDA Selinexor’s with One on the Totality of Potential Role in Approved Class of the Data and sNDA Myelofibrosis Therapy Filing Plan Present SENTRY results at medical meeting and submit manuscript for publication Potential compendia inclusion in the second half of 2026 Selinexor has not been approved by the U.S. FDA or any other regulatory authority for use in myelofibrosis. 22 ©2026 KARYOPHARM THERAPEUTICS INC.
Our sincere thanks… … to patients, caregivers, investigators and clinical trial sites for their participation in SENTRY and to the Karyopharm team for their commitment to advancing innovative therapies for patients with significant unmet medical needs.
Exhibit 99.3
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Karyopharm Announces $30 Million Private Placement with RA Capital
NEWTON, Mass. – March 24, 2026 – Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it has entered into a securities purchase agreement with RA Capital Management for a private placement that is expected to result in gross proceeds of approximately $30 million before deducting placement agent fees and offering expenses, and an additional approximately $44 million of gross proceeds if the accompanying warrants are exercised in full.
In the private placement, the Company agreed to sell 1,030,354 shares of common stock at a price of $6.785 per share, 3,391,164 pre-funded warrants at a price of $6.7849 per pre-funded warrant, and accompanying warrants to purchase 4,421,518 shares of common stock with an exercise price of $10.00 per share. The pre-funded warrants will have an exercise price of $0.0001 per share of common stock, will be immediately exercisable and will not expire. The accompanying warrants will be immediately exercisable and will expire 30 days following the public announcement by the Company of topline results from the Phase 3 XPORT-EC-042 clinical trial of selinexor in patients with endometrial cancer.
The private placement is expected to close on or about March 26, 2026, subject to the satisfaction of customary closing conditions. The private placement was priced at-the-market under Nasdaq rules. The Company expects that the net proceeds of the private placement, together with its existing liquidity, including cash, cash equivalents and investments, as well as cash flow from net product revenue and license and other revenue, will enable it to fund its current operating plans into late Q3 2026.
The Company intends to use the proceeds from the private placement for general corporate purposes, including to support the Company’s ongoing and planned clinical trial activities.
Jefferies and Piper Sandler acted as placement agents for the private placement.
The offer and sale of the shares of common stock, pre-funded warrants, warrants, or any other securities (including the shares of common stock issuable upon exercise of the pre-funded warrants and warrants) are not being registered under the Securities Act of 1933, as amended (the “Securities Act”), or any state securities laws. The shares of common stock, pre-funded warrants, warrants, or any other securities (including the shares of common stock issuable upon exercise of the pre-funded warrants and warrants) may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Securities Act and any applicable state securities laws.
This press release does not constitute an offer to sell or the solicitation of an offer to buy shares of common stock, pre-funded warrants, warrants, or any other securities, nor shall there be any offer, solicitation or sale of shares of common stock, pre-funded warrants, warrants, or any other securities (including the shares of common stock issuable upon exercise of the pre-funded warrants and warrants) in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful.
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,
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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).
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 expected closing date of the private placement, the Company’s expected cash runway following closing of the private placement, and the Company’s expected use of proceeds from the private placement. 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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| CONTACTS: |
| Investors: |
| Brendan Strong |
| Senior Vice President, Investor Relations 617.762.2661 |
| brendan.strong@karyopharm.com |
| Media: |
| Mary Ann Ondish |
| Head of Corporate Communications 914.552.4625 |
| Maryann.ondish@karyopharm.com |
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FAQ
What did Karyopharm Therapeutics (KPTI) announce from the Phase 3 SENTRY myelofibrosis trial?
Did Karyopharm’s SENTRY trial improve symptoms compared with ruxolitinib alone?
What are the key terms of Karyopharm’s $30 million private placement with RA Capital?
How long does Karyopharm expect its cash to last after the new financing?
What change is Karyopharm making to the XPOVIO diffuse large B-cell lymphoma indication?
How does the private placement affect Karyopharm’s credit and forbearance agreements?
How many Karyopharm shares are currently outstanding and what ATM activity occurred?
Filing Exhibits & Attachments
10 documentsAgreements & Contracts
