Ruxolitinib

– sNDA Submitted under the Accelerated Approval Pathway; Priority Review Requested – NEWTON, Mass., Aug. 31, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking Accelerated Approval for XPOVIO® (selinexor) in combination with ruxolitinib for patients with myelofibrosis. Karyopharm requested Priority Review of the application, which, if granted, could result in a six-month review process. "Today's submission is an important step toward our goal of bringing the combination of selinexor plus ruxolitinib to patients with myelofibrosis who continue to face a significant unmet need," said Reshma Rangwala, M.D., Ph.D., Chief Medical Officer and Head of Research of Karyopharm. "The SENTRY trial generated compelling and consistent results, including rapid, deep and sustained spleen responses across a broad range of patients, together with a promising overall survival signal and important evidence of disease modification. We believe the strength of these data underscores the potential of this novel combination to deliver meaningful long-term benefits and fundamentally change the treatment of patients with myelofibrosis." Following the topline results of the Phase 3 SENTRY trial, the Company has engaged productively with the FDA. The sNDA submitted is based, in part, on data from the SENTRY trial that the Company believes supports a positive benefit-risk profile for the combination, including a promising signal of overall survival. The Company expects approval under the Accelerated Approval pathway would require the FDA to agree that spleen volume reduction ≥ 35% (SVR35) is a reasonably likely surrogate endpoint to predict overall survival. The Company plans to use long-term overall survival data from the Phase 3 SENTRY trial to verify clinical benefit and support conversion from accelerated to traditional approval and expects to continue working with the FDA during its review of the sNDA to finalize the confirmatory evidence plan. Karyopharm expects to receive notice of the FDA's decision on sNDA filing acceptance and, if accepted, the anticipated review timelines in the fourth quarter of 2026, following the FDA's 60-day filing review period. In May 2022, the FDA granted selinexor Orphan Drug Designation for the treatment of myelofibrosis, and in October 2022, the European Commission granted Orphan Medicinal Product Designation for selinexor for the treatment of myelofibrosis. In addition, in July 2023, the Company received Fast Track Designation from the FDA for selinexor for the treatment of patients with myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis. 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 (N=353). 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. The results from the Phase 3 SENTRY trial were presented at the 2026 American Society of Clinical Oncology Annual Meeting and were simultaneously published in the peer-reviewed Journal of Clinical Oncology. In addition, the results were presented at the 2026 European Hematology Association Congress, where the presentation was recognized as one of the six best abstracts at the meeting. About Myelofibrosis Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 19,000 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. 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 and marketed by Karyopharm in the U.S. 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; and (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma. 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. For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326; Email: [email protected] 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). 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%. Use In Specific Populations Lactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit . To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or . About Karyopharm Therapeutics Karyopharm Therapeutics is a commercial-stage pharmaceutical company pioneering the science of nuclear export inhibition to develop differentiated therapies for patients with cancer. The Company's lead therapy, XPOVIO® (selinexor), is a first-in-class inhibitor of exportin 1 (XPO1). XPOVIO is marketed by the Company in the U.S. for adults with relapsed or refractory multiple myeloma and is approved as XPOVIO or NEXPOVIO® in more than 50 ex-U.S. countries and territories. Building on its leadership in XPO1 biology, Karyopharm is advancing selinexor's potential in hematological cancers, including in myelofibrosis. The Company is also exploring opportunities to evaluate XPO1 inhibition across myeloproliferative neoplasms using next-generation compounds, including eltanexor. Headquartered in Newton, Massachusetts, Karyopharm has an established, efficient, and scalable commercial infrastructure to bring novel therapeutic options to patients with cancer. For more information, visit and follow Karyopharm 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 Karyopharm's expectations with respect to the FDA's review timing and the completeness and acceptability of its sNDA submission for selinexor in combination with ruxolitinib in myelofibrosis; Karyopharm's ongoing engagement with the FDA; the potential availability of the accelerated approval pathway; whether long-term overall survival data from the SENTRY trial will verify clinical benefit; the potential availability of priority review of the sNDA; expectations with respect to commercialization efforts; and the ability of selinexor and eltanexor to treat patients with multiple myeloma, myelofibrosis, and other diseases. 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 Quarterly Report on Form 10-Q for the quarter ended June 30, 2026, which was filed with the Securities and Exchange Commission (SEC) on August 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. CONTACT: Brendan Strong Senior Vice President, Investor Relations 617.762.2661 [email protected] SOURCE Karyopharm Therapeutics Inc. 21% more press release views with Request a Demo

Cancer treatments often show early promise: tumors shrink and symptoms ease. But in many cases, the disease comes roaring back, driven by treatment-resistant cells. Part of what makes cancer so difficult to cure is that cells within a tumor are not cookie-cutter – they vary widely. Cancer cells within a tumor exist in multiple distinct malignant states, a property called “heterogeneity.” These states can also switch into one another, a property called “plasticity” — like a phone moving between airplane mode, power-saving mode, or full-performance mode. The cells share the same lineage and DNA, yet may develop into different states depending on which regulatory proteins are active in each cell, much like the normal cells in our body can have widely different states and yet carry the same DNA. Drugs used to treat a tumor are often effective only for a few of the specific states, so cells in other states remain and repopulate, making the tumor difficult to eradicate. Researchers at Biohub and collaborators from Columbia University and other institutions have developed a novel AI-based system to model how individual cells within a tumor behave and interact with drugs. The work, published in a pair of papers in Nature Genetics, supports a new hypothesis the team calls “cancer quantum biology” — that tumors of the same type have virtually identical sets of cell states across patients, and that those states interact in ways that defeat treatment. In the pancreatic cancer study, the team showed that cancer cell states can spontaneously reprogram themselves into one another, allowing tumors to evade drugs targeting any single state. In the Diffuse Midline Glioma (DMG) study, the team went further: using AI to predict drugs that target each individual state, validating those predictions experimentally, and showing that drug combinations targeting multiple states simultaneously produced synergistic effects, doubling the survival achieved by individual drugs. The method worked across two difficult-to-treat cancers: pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer, and DMG, a rare brain tumor that occurs most frequently in children between the ages of five and 10. “These tumors often kill the patient within nine months,” says study co-author Andrea Califano, head of Biohub, New York. “There is a desperate need for new ways to target these malignancies.” The work, published in a pair of papers in Nature Genetics (April 2026 and August 2026), represents the first time researchers have successfully shown that cancer cell states and their vulnerabilities, known as “Master Regulators,” are ultraconserved across patients and predicted drugs that target them in each of the coexisting cancer cell states, leading to effective combination therapies. A central Biohub goal is understanding how to engineer immune cells to detect cancer as it arises, and to precisely target diseased cells as early as possible. Tumors themselves are exceptional immune-cell engineers, leveraging various cell states to create microenvironments that ward off immune attacks. By mapping the regulatory proteins that govern these cell states, the new research brings the field closer to this goal — and the authors had previously shown that targeting the Master Regulators of a tumor greatly improves response to immunotherapy. First, the researchers needed to map how many and what types of cell states were present in each form of cancer. They did this by tracking which Master Regulator proteins governed the state of each single cell. Using single-cell RNA sequencing data from patient tumors, researchers identified these Master Regulators with two state-of-the-art AI-based algorithms developed in Califano’s lab and now used across Biohub to analyze single-cell data: ARACNe and VIPER/metaVIPER. By combining network modeling with computational analysis, these tools make it possible to determine how individual cells maintain different states within a tumor. ARACNe reconstructs gene-regulatory networks by identifying direct links between transcription factors and their target genes. It uses information theory, a branch of mathematics, to produce a map of how the cell is controlled. VIPER then identifies the cell’s master regulators — proteins that control a cell’s behavior and regulate which state it is in — based on the differential expression of their target genes. The team found that the same malignant cell states were virtually identically conserved across all patients in multiple cohorts representing the same tumor: across cohorts representing more than a hundred pancreatic cancer patients and fourteen diffuse midline gliomas. Though the fraction of cells in each state varied, every patient with glioma, for example, had cells in the same seven states. In pancreatic cancer, virtually all cells with high-quality data fell into the same six cell states. This was a significant finding — and a clarifying one. The field has long assumed that the internal variety of tumors was essentially limitless and different in every person, driving the push toward personalized medicine. This work suggests the opposite may be closer to the truth. With the cell states and their master regulators now known, it was time to test approved drugs to see which might work against each tumor cell state. For this step, the team focused on DMG. They screened 372 clinically relevant oncology drugs and analyzed how the cells responded to each drug after 24 hours. Instead of simply measuring whether cells died, the researchers analyzed how each drug changed the activity of master regulators within the cells, revealing whether a drug disrupted the regulatory networks that maintain specific tumor cell states. The team then fed these drug profiles into two other clinical-grade computational tools—OncoTarget and OncoTreat—that predict which drugs can best switch off the master regulators that keep each tumor cell state alive. One of these network-based algorithms identifies drugs that directly inhibit a key regulator, and the other flags those that can reverse the broader regulatory program sustaining a given cell state. Both have been tested in a large preclinical study and are now being applied clinically to guide cancer treatment. Using these technologies, the team systematically identified drugs capable of reversing individual cell states in DMG, achieving roughly 90% predictive accuracy and specificity in single-cell state depletion assays, which measure the proportion of cells remaining in a specific state after treatment. Next, those drug predictions needed to be validated. In a mouse model of DMG, in which the tumor was under the skin, eight out of nine drugs tested precisely depleted the predicted target states. “That is pretty remarkable, because we started with 372 possible drugs, virtually all those that are currently clinically relevant in oncology,” says Califano. With that success, the team then started combining drugs to target two states at once, and found that some drug combinations increased survival. Across these experiments, four out of six drug combinations tested showed much stronger benefit than single-drug treatments. The team then tested the drugs in a second mouse model, in which the tumor was in the brain. Here, they noticed a clear pattern: When a drug depleted one cell state, other, non-targeted states became more dominant, meaning that the tumors shifted toward cells that were able to survive the treatment, the very nature of drug resistance. Drug combinations were tested in DMG orthotopic models. This confirms why combination therapy is often needed across various cancers – eliminating only one cell state allows the others to take over. In the case of DMG, a combination of two drugs, avapritinib and ruxolitinib, offered the greatest survival gains. While FDA-approved for other conditions, these drugs have not previously been used to treat DMG. To directly apply their findings to human health, the Biohub team is now working with partners to build a clinical trial for the newly discovered DMG drug regimen. “Targeting different cell states simultaneously or sequentially would appear to be the only way forward,” says Califano. “Every tumor we’ve seen is made up of multiple states, and unless you hit more than one at a time, the cancer finds a way back.”