A Phase 1 Study with a Pilot Expansion Phase of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone (IoVeX) for Relapsed B-cell Acute Lymphoblastic Leukemia (B-ALL)

The goal of this clinical trial is to learn if the combination of drugs Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone (IoVeX) are safe to treat relapsed B-cell Acute Lymphoblastic Leukemia (B-ALL) in pediatric and adult patients. It will also learn if these drugs are well tolerated. The main questions it aims to answer are:
Is the drug combination of Inotuzumab Ozogamicin, Venetoclax, and Dexamethasone (IoVeX) safe when given to patients?
What medical problems do patients taking IoVeX experience?
Participants will:
Receive this combination of drugs for 1 cycle which is 28 days at various timepoints. If participants tolerate cycle 1 they will be eligible to continue to cycle 2 which is also 28 days.
Have checkups and tests at the beginning of the study and throughout the course of each cycle.

Start Date01 Apr 2025

Sponsor / Collaborator

Cincinnati Children's Hospital Medical Center

NCT06715709

/ Not yet recruitingPhase 4IIT

Corticosteroids in Total Knee Arthroplasty: How Many Dexamethasone Doses Should Be Given Perioperatively? a Randomized Controlled Trial

The purpose of this study is to determine the most efficient and safest dexamethasone dose given perioperatively during total knee arthroplasty that reduces postoperative option consumption and pain, improves postoperative nausea and vomiting, and minimizes postoperative complications

Start Date01 Apr 2025

Sponsor / Collaborator

Mayo Clinic

NCT06879379

/ RecruitingPhase 2/3IIT

A Randomized, Multicenter Study Comparing Post-Transplant KPD Regimen Consolidation With No Consolidation in Newly Diagnosed Multiple Myeloma (NDMM) Transplant-eligible Patients

This study aims to evaluate the efficacy and safety of post-transplant consolidation therapy with the KPD regimen (carfilzomib, pomalidomide, and dexamethasone) versus no consolidation, followed by maintenance therapy, in patients with transplant-eligible newly diagnosed multiple myeloma (TE-NDMM). The primary goal is to compare minimal residual disease (MRD) negativity rates and overall treatment outcomes between the two groups.

Start Date01 Mar 2025

Sponsor / Collaborator

Peking University People's Hospital

100 Clinical Results associated with Dexamethasone Cipecilate

100 Translational Medicine associated with Dexamethasone Cipecilate

100 Patents (Medical) associated with Dexamethasone Cipecilate

Literatures (Medical) associated with Dexamethasone Cipecilate

01 Feb 2018·European Journal of Pharmaceutical SciencesQ2 · MEDICINE

Opportunity and challenges of nasal powders: Drug formulation and delivery

Q2 · MEDICINE

Review

Author: Buttini, Francesca ; Rossi, Alessandra ; Bortolotti, Fabrizio ; Colombo, Gaia ; Sonvico, Fabio ; Tratta, Elena ; Manniello, Michele Dario ; Russo, Paola ; Tiozzo Fasiolo, Laura

In the field of nasal drug delivery, among the preparations defined by the European Pharmacopoeia, nasal powders facilitate the formulation of poorly water-soluble active compounds. They often display a simple composition in excipients (if any), allow for the administration of larger drug doses and enhance drug diffusion and absorption across the mucosa, improving bioavailability compared to nasal liquids. Despite the positive features, however, nasal products in this form still struggle to enter the market: the few available on the market are Onzetra Xsail® (sumatriptan) for migraine relief and, for the treatment of rhinitis, Rhinocort® Turbuhaler® (budesonide), Teijin Rhinocort® (beclomethasone dipropionate) and Erizas® (dexamethasone cipecilate). Hence, this review tries to understand why nasal powder formulations are still less common than liquid ones by analyzing whether this depends on the lack of (i) real evidence of superior therapeutic benefit of powders, (ii) therapeutic and/or commercial interest, (iii) efficient manufacturing methods or (iv) availability of suitable and affordable delivery devices. To this purpose, the reader's attention will be guided through nasal powder formulation strategies and manufacturing techniques, eventually giving up-to-date evidences of therapeutic efficacy in vivo. Advancements in the technology of insufflation devices will also be provided as nasal drug products are typical drug-device combinations.

01 Oct 2011·XenobioticaQ4 · MEDICINE

In vitrometabolism of dexamethasone cipecilate, a novel synthetic corticosteroid, in human liver and nasal mucosa

Q4 · MEDICINE

Article

Author: Kawakita, Naoko ; Takahashi, Yousuke ; Tsujioka, Tomoo ; Nakamura, Akio ; Nakagawa, Takashi ; Sasagawa, Takahiro ; Yamada, Tetsuhiro ; Nonaka, Kiyoko

Dexamethasone cipecilate (DX-CP, 9-fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione 21-cyclohexanecarboxylate 17-cyclopropanecarboxylate) is a novel synthetic corticosteroid used to treat allergic rhinitis. The pharmacological effect of DX-CP is considered to be mainly due to its active de-esterified metabolite (DX-17-CPC). To investigate the in vitro metabolism of DX-CP in human liver, DX-CP was incubated with human liver microsomes and S9. In addition, a metabolism study of DX-CP with human nasal mucosa was carried out in order to elucidate whether DX-17-CPC is formed in nasal mucosa, the site of action of DX-CP. DX-17-CPC was the major metabolite in both liver microsomes and S9. Two new epoxide metabolites, UK1 and UK2, were detected in liver S9, while only UK1 was detected in liver microsomes. This suggests that cytosol enzymes are responsible for the formation of UK2. In human nasal mucosa, DX-CP was mainly transformed into DX-17-CPC. By using recombinant human carboxylesterases (CESs), the reaction was shown to be catalyzed by CES2. These results provide the evidence that the active metabolite DX-17-CPC is the main contributor to the pharmacological action after the intranasal administration of DX-CP to humans.

01 Dec 2010·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Clinical pharmacology study of the corticosteroid nasal spray dexamethasone cipecilate (NS-126): examination of the durability of efficacy in the nasal induction test

Q2 · MEDICINE

Article

Author: Minoru Okuda ; Chikuma Hamada ; Kimihiro Okubo ; Minoru Gotoh

BACKGROUNDDexamethasone cipecilate is a corticosteroid nasal spray whose local efficacy durability has been improved by introduction of a liposoluble functional group to its chemical structure. This study was conducted to evaluate the efficacy of once-daily treatment with this drug in patients with perennial allergic rhinitis by a challenge test with house dust antigen (Phase I clinical pharmacology study).METHODSThis study was designed as a randomised placebo-controlled double-blind study in 28 patients with perennial allergic rhinitis. Either 200 μg dexamethasone cipecilate or placebo was administered once daily for 7 days, and the antigen challenge test conducted 23 h after the dose on each day. We evaluated the efficacy primarily through assessment of suppression of immediate nasal symptoms.RESULTSWhen efficacy durability was evaluated by physicians based on a general assessment of the effects of suppression of nasal symptoms, the percentage of patients with efficacy lasting for 24 h differed significantly between the dexamethasone cipecilate group (69.2%, 9 out of 13) and the placebo group (15.4%, 2 out of 13) (p = 0.015).CONCLUSIONSDexamethasone cipecilate was shown to be a corticosteroid having sustainable local efficacy. The results suggest that once-daily administration of dexamethasone cipecilate is effective in patients with allergic rhinitis, and that its efficacy lasts for 24 h.

News (Medical) associated with Dexamethasone Cipecilate

12 Mar 2025

·www.fiercepharma.com

J&J, Legend to invest $150M in Belgium cell therapy facility as new Carvykti rival looms

Johnson & Johnson and Legend Biotech's additional investment comes just as the so-called Tech Lane facility is set to begin clinical production of Carvykti in a few weeks. On track to meet their long-stated capacity goal for multiple myeloma therapy Carvykti in 2025, Johnson & Johnson and Legend Biotech are already planning the next phase of their cell therapy manufacturing expansion.Based on internal projections for demand, the two companies have approved about $150 million in additional investments to expand the future capacity of a brand-new facility in Ghent, Belgium, Legend CEO Ying Huang, Ph.D., and interim Chief Financial Officer Jessie Yeung said on an investor call Tuesday.J&J and Legend decided on the new investment just as the so-called Tech Lane facility is set to begin clinical production of Carvykti in a few weeks. The site is expected to gain approval to initiate commercial supply by the end of 2025, according to Huang.For the latest expansion, early engineering and design work has begun, and construction is slated to start in the second half of 2025 and expected to be complete in 2028, Yeung said. The addition will primarily provide supplies for the EU market, a Legend spokesperson told Fierce Pharma.Over the last several years, J&J and Legend have been busy working to ramp up their cell therapy manufacturing capacity. Since Carvykti’s initial FDA approval in early 2022, supply constraints have limited the CAR-T therapy’s revenue growth. What’s more, an expanded FDA nod in April 2024 in second-line multiple myeloma roughly tripled the med’s eligible patient population.In one of the pair’s recent efforts to boost supply, contract manufacturer Novartis recently won FDA approval to make commercial supply of Carvykti at its site in Morris Plains, New Jersey, Huang said on the call. Also in New Jersey, J&J and Legend said in the fall of 2022 that they would double the investment in their flagship Raritan manufacturing facility to a total of $500 million. Legend now expects regulatory approval of a new section at that site in the second half of this year.The companies have another site in Ghent, called the Obelisc facility, which began commercial production in the third quarter of 2024 and is now operating at full capacity, according to Legend.These recent expansions will help the companies reach a capacity to be able to produce 10,000 doses of Carvykti on an annualized basis this year, a goal that was outlined in 2023.“By the end of this year, we’ll be in a situation where supply is fully meeting the demand where we are, and then we’ll be able to keep pace,” Alan Bash, Legend’s president of Carvykti, said on Tuesday’s call. But as analysts noted on the call, Wall Street’s 2026 consensus sales projection for Carvykti indicates that market watchers were unsure about whether patient demand will start to taper off.As of Tuesday, Carvykti can be administered at 104 certified treatment centers in the U.S. Meanwhile, growing levels of administration in the outpatient setting—and increased use at community practices—offer “significant upside” to the drug's growth trajectory, Bash said.Recipients of CAR-T therapies need to be monitored for the potentially life-threatening side effect of cytokine release syndrome. Because of Carvykti’s delayed onset of te syndrome, community providers are able to utilize outpatient administration, thereby freeing up limited inpatient space.This factor can help increase overall treatment capacity and therefore boost demand. The proportion of outpatient Carvykti use has increased from about 30% a year ago to more than 50% today, according to Bash.J&J and Legend have a three-stage plan to increase adoption in the community setting, where most multiple myeloma patients are treated. Right now, the drugmakers are reaching out to more than 8,000 community oncologists to educate them on Carvykti and to help them refer patients to certified treatment centers.In the second stage, starting later this year, the pair will identify certain regional hospitals and community accounts that are closely affiliated with large hospitals to administer Carvykti on-site, Bash said. For the third stage, which will begin next year, the goal is to have the drug more widely administered in community oncology practices, he added. Looming competition Another key reason analysts have reservations about Carvykti in 2026 is the expected entry of Gilead Sciences and Arcellx’s rival BCMA CAR-T anito-cel. In a pivotal phase 2 trial in late-line myeloma, anito-cel showed what analysts viewed as competitive efficacy and better safety to Carvykti, with the important caveat that cross-trial comparisons carry inherent flaws.On Tuesday’s call, Huang played down the potential threat of anito-cel for Carvykti in 2026. When approved, anito-cel would be entering the late-line setting, whereas the majority of Carvykti’s revenue mix will come from earlier lines, he argued. By the end of 2025, Legend expects about two-thirds to three-quarters of Carvykti revenue will come from second- to fourth-line treatment, he said.In anito-cel's phase 2 trial, one factor that stood out for the drug was the absence of some delayed neurotoxicities, including Parkinsonism, which has recently emerged as a concern for Carvykti. During Tuesday’s call, Legend executives pointed to a recent single-site study by the Colorado Blood Cancer Institute. The small study of 39 patients suggested that unrestrained absolute lymphocyte count (ALC) expansion is predictable of neurotoxicites following Carvykti treatment and that prophylactic treatment with the steroid dexamethasone may be able to mitigate the effect. The study did not separate delayed neurotoxocities from other neurologic complications.Legend is talking to multiple centers to potentially study this phenomenon in an investigator-initiated trial, and it has incorporated the mitigation strategy into ongoing Cartitude trial programs for Carvykti, Chief Medical Officer Mythili Koneru, M.D., Ph.D., said on Tuesday’s call.As to the real world, Koneru noted that an ALC-based monitoring and mitigation strategy is easily applicable, because it’s “a very typical lab result that is checked very frequently and commonly at all centers, including academic centers as well as in a community setting.”

Phase 2Cell TherapyDrug Approval

05 Mar 2025

·www.fiercepharma.com

FDA blasts Edenbridge over 'misleading' exhibit booth panel

Edenbridge Pharmaceuticals’ omission of risk information on an exhibit booth panel is one focus of an FDA letter. The FDA has sent its first untitled letter of 2025, hitting Edenbridge Pharmaceuticals with a notice after assessing an exhibit booth panel’s compliance with the rules on promoting prescription drugs.Edenbridge, which rebranded as Dexcel Pharma in October, created the panel to communicate data on its multiple myeloma drug Hemady. The product is an oral formulation of the steroid dexamethasone. By including 20 mg of dexamethasone in each tablet, rather than the 4 mg found in some other products, the company has cut the number of pills multiple myeloma patients need to take.The exhibit displays data on the claimed advantages of Hemady. However, the FDA, having reviewed the panel and a complaint made via the Bad Ad program, found fault with some information Edenbridge left out and the robustness of a study that underpinned some of the claims.The panel’s omission of risk information is one focus of the FDA’s letter. The exhibit states that Hemady can cut the number of dexamethasone tablets multiple myeloma patients take by 80%. However, the panel is misleading, according to the FDA, because it presents those data but “entirely omits all risk information.” The agency said the lack of risk information creates a misleading impression about the safety of the drug. The FDA also took aim at a retrospective, real-world comparison of adherence to Hemady and generic dexamethasone. Edenbridge presented the findings of the analysis in a table on the exhibit. The table compares the medication possession rate (MPR), a measure of adherence, and the percentage of people with an MPR of at least 80% for 4 mg dexamethasone and Hemady.The ratio and percentage of patients with an MPR of at least 80% are higher in the Hemady cohort than in the 4-mg arm, according to Edenbridge. The company compared the cohorts, generating p-values of 0.0002 and 0.007. P-values of 0.05 and lower are typically considered statistically significant.Yet, the FDA said the study “does not support conclusions regarding comparative adherence” to the two formulations because of design and methodology limitations. The agency listed problems with patient selection, noting that the study had failed to verify whether people on Hemady actually had been diagnosed with multiple myeloma and had included both newly diagnosed and relapsed or refractory patients in the 4 mg dexamethasone cohort, without distinguishing between the different phases of disease.The FDA also highlighted the “notably unbalanced sample size”: The 4 mg dexamethasone arm contained 3,775 patients, but there were only 43 people in the Hemady group. The FDA said “such unbalanced sample sizes can lead to overestimation of adherence in favor of the Hemady group.” Citing such issues, the agency said the study did not establish that adherence was better on Hemady than 4 mg dexamethasone. The FDA sent the letter on Feb. 3 and gave Edenbridge 15 working days to respond. The agency asked Edenbridge to list all promotional communications that contain representations like those described in the letter. The Hemady website for healthcare professionals used to display results from the adherence study, but Edenbridge removed that page some time after Dec. 3, 2024, per snapshots saved in the Internet Archive.

19 Feb 2025

·www.prnewswire.com

Karyopharm Reports Fourth Quarter and Full Year 2024 Financial Results, Announces Update to Phase 3 XPORT-EC-042 Trial and Highlights Recent Company Progress

– Total Revenue of $145 Million and U.S. XPOVIO® (selinexor) Net Product Revenue of $113 Million for Full Year 2024 – – Top-Line Data Readout from Phase 3 SENTRY Trial Evaluating Selinexor in Combination with Ruxolitinib in Patients with JAKi-Naïve Myelofibrosis Anticipated in 2H 2025; Company on Track to Complete Enrollment in 1H 2025 – – Company Announces Update to Phase 3 XPORT-EC-042 Trial of Selinexor as Maintenance Therapy in Advanced or Recurrent TP53 Wild-Type Endometrial Cancer. Following Dialogue with the FDA Regarding the Evolving Treatment Landscape, Trial to Focus Enrollment on Patients with Either pMMR Tumors or Patients with dMMR Tumors that are Medically Ineligible for Checkpoint Inhibitors. Increasing Sample Size to 276; Top-Line Data Now Expected in Mid-2026 – – Company Provides Full-Year 2025 Total Revenue Guidance of $140 Million to $155 Million, Including U.S. XPOVIO Net Product Revenue Guidance of $115 Million to $130 Million – – Conference Call Scheduled for Today at 8:00 a.m. ET – NEWTON, Mass., Feb. 19, 2025 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today reported financial results for the fourth quarter and full year ended December 31, 2024. In addition, Karyopharm highlighted select corporate milestones and provided an overview of its key clinical development programs. "In 2025, our teams remain focused on the transformative opportunity to redefine the standard of care in myelofibrosis, with top-line data from our Phase 3 SENTRY trial evaluating selinexor in combination with ruxolitinib on-track for the second half of 2025. We look forward to completing enrollment of our SENTRY trial in the first half of this year and leveraging our demonstrated commercialization capabilities in multiple myeloma to support a rapid launch, subject to approval," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "In endometrial cancer, today we announced our updated plans for our Phase 3 trial and intend to primarily focus on the TP53 wild-type pMMR population, which represents approximately 50% of all women with endometrial cancer, and expect to share top-line data in mid-2026." Fourth Quarter 2024 and Recent Highlights XPOVIO Commercial Performance Achieved U.S. net product revenue for the year ended December 31, 2024 of $113 million, compared to $112 million for the year ended December 31, 2023. U.S. net product revenue for the fourth quarter of 2024 was $29 million, compared to $25 million for the fourth quarter of 2023. Demand for XPOVIO was consistent in 2024 versus 2023, with demand growth in the second half of 2024 in both the community setting, which represents approximately 60% of XPOVIO net product revenue, and the academic setting, offsetting a decline in demand in the first half of the year due to an intensified competitive landscape. XPOVIO net product revenue was impacted year-over-year by higher gross-to-net adjustments in 2024, driven primarily by increased 340B discounts and Medicare rebates. Expanded global patient access for selinexor in 2024 with favorable reimbursement decisions in the United Kingdom, France, Italy, China and South Korea and additional regulatory approvals in UAE, Kuwait, China, Malaysia, Turkey, Thailand, and South Korea in various indications, increasing the number of countries where selinexor is now approved in more than 45 countries. Research and Development (R&D) Highlights Myelofibrosis Updated the co-primary endpoint in the Phase 3 SENTRY trial (XPORT-MF-034; NCT04562389) to absolute mean change in total symptom score (Abs-TSS) following alignment with the U.S. Food and Drug Administration (FDA) and proactively increased the total sample size to approximately 350 patients to further increase the statistical powering. Abs-TSS measures the average improvement in symptom scores over 24 weeks relative to the baseline symptom score. Abs-TSS is viewed by many key opinion leaders (KOLs) and patient advocacy organizations as a more accurate assessment of symptom improvement in head-to-head clinical trials, such as SENTRY which is evaluating selinexor in combination with ruxolitinib in patients with JAK inhibitor (JAKi) naïve myelofibrosis versus ruxolitinib alone. Spleen volume reduction ≥35% (SVR35) at week 24 remains the other co-primary endpoint. These two co-primary endpoints will be tested sequentially starting with SVR35 followed by Abs-TSS. Hosted an investor event with leading KOLs in October 2024 to discuss the change in the co-primary endpoint in the Phase 3 SENTRY trial to Abs-TSS and highlight the strength of the data from the Company's Phase 1 trial in myelofibrosis. Data from the Company's Phase 1 trial, evaluating the combination of selinexor 60 mg plus ruxolitinib in JAKi naïve myelofibrosis patients, demonstrated that 79% of patients in the intent to treat population (n=14) achieved SVR35 and an average Abs-TSS improvement of 18.5 points in the efficacy evaluable population (n=9), at week 24 relative to baseline. Acknowledging the small sample size, these data suggest that the combination is favorable compared to historical ruxolitinib monotherapy data which indicates that less than half of patients achieve SVR35 and an Abs-TSS improvement of 11 to 14 points1. As of the most recent data cut off, the safety profile remained consistent and no new safety signals were identified. The Company continues to enroll patients into the 60 mg cohort of the Phase 2 SENTRY-2 trial of selinexor monotherapy in JAKi naïve patients with moderate thrombocytopenia (XPORT-MF-044; NCT05980806). 1Phase 3 MANIFEST trial. Rampal R, et al. ASH 2023. Oral 628; Phase 3 TRANSFORM-1 trial Pemmaraju N, et al. ASH 2023 abstract 620. Endometrial Cancer The Company is modifying the design of its Phase 3 XPORT-EC-042 trial evaluating selinexor as a maintenance-only therapy following systemic therapy versus placebo in patients with TP53 wild-type advanced or recurrent endometrial cancer. In late 2024 and early 2025, the Company engaged in communications with the FDA regarding the design adequacy of XPORT-EC-042 given the changing standard of care in endometrial cancer, particularly the approval of checkpoint inhibitors for patients with advanced or recurrent endometrial cancer regardless of mismatch repair status. In light of the FDA's acknowledgement that the magnitude of benefit achieved from checkpoint inhibitors is less for patients with pMMR tumors than patients with dMMR tumors, consistent with the biology and mechanism of action of checkpoint inhibitors, the Company's modifications include defining two patient populations for which the primary endpoint of progression free survival (PFS), tested sequentially, and key secondary endpoint of overall survival (OS) will be evaluated: a modified intent to treat population (mITT) that will include patients with: TP53 wild-type tumors with proficient mismatch repair status (pMMR); or, TP53 wild-type tumors with deficient mismatch repair status (dMMR), who are medically ineligible to receive checkpoint inhibitors. the trial's original intent to treat (ITT) population, which will include all patients enrolled in the trial whose tumors are TP53 wild-type, regardless of MMR status. The Company is increasing the trial sample size from 220 patients to approximately 276 patients, to ensure that the mITT population includes approximately 220 patients who are either: a) TP53 wild-type pMMR or b) TP53 wild-type dMMR and medically ineligible to receive a checkpoint inhibitor. The increase in sample size maintains sufficient power for the primary endpoint of PFS in the mITT population. To date, approximately 80% of patients enrolled meet the new eligibility definition for the mITT population. The proposed modifications are intended to address certain of the FDA's feedback regarding the evolving treatment landscape, including the approval of multiple checkpoint inhibitors for advanced/recurrent endometrial cancer patients with pMMR and/or dMMR tumors in 2023 and 2024. Enrollment continues in the XPORT-EC-042 trial and, depending on the strength of the data, the Company intends to pursue regulatory approval. As a result of the proposed modifications, the Company now expects topline data in mid-2026. Multiple Myeloma Completed enrollment of the Phase 3 XPORT-MM-031 trial (EMN29; NCT05028348) of approximately 120 patients, leveraging the data published on selinexor 40 mg, pomalidomide and dexamethasone (SPd40) in 2024. The Phase 3 XPORT-MM-031 trial is being conducted in collaboration with the European Myeloma Network and is evaluating the all-oral combination SPd40 in patients with previously treated multiple myeloma who received an anti-CD38 in their immediate prior line of therapy. Pending ongoing engagement with regulatory agencies on the updated protocol and statistical plan, the Company intends to provide an update on this trial. Anticipated Catalysts and Operational Objectives in 2025 Myelofibrosis Announce completion of enrollment of the Phase 3 SENTRY trial evaluating selinexor in combination with ruxolitinib in JAKi naive myelofibrosis patients in 1H 2025. Report preliminary data on a subset of participants in the 60 mg cohort from the Phase 2 SENTRY-2 trial evaluating selinexor as a monotherapy in patients with JAKi naïve myelofibrosis with moderate thrombocytopenia in 1H 2025. Report top-line results from the Phase 3 SENTRY trial in 2H 2025. Multiple Myeloma Maintain the Company's commercial foundation in the competitive multiple myeloma marketplace and drive increased XPOVIO revenues. Continue global launches and reimbursement approvals for selinexor by partners in ex-U.S. territories. Continue to follow patients that are enrolled in the Phase 3 XPORT-MM-031 (EMN29) trial. Pending ongoing engagement with regulatory agencies on the updated protocol and statistical plan, the Company intends to provide an update on this trial. Endometrial Cancer Continue to enroll patients into the Phase 3 XPORT-EC-042 trial of selinexor as a maintenance monotherapy for patients with TP53 wild-type advanced or recurrent endometrial cancer. 2025 Financial Outlook Based on its current operating plans, Karyopharm expects the following for full year 2025: Total revenue to be in the range of $140 million to $155 million. Total revenue consists of U.S. XPOVIO net product revenue and license, royalty and milestone revenue earned from partners. U.S. XPOVIO net product revenue to be in the range of $115 million to $130 million. R&D and selling, general and administrative (SG&A) expenses to be in the range of $240 million to $255 million, which includes approximately $20 million of estimated non-cash stock-based compensation expense. The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO net product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into the first quarter of 2026.2 2Excluding re-payment of $24.5 million aggregate principal amount of the Company's remaining senior convertible notes due October 2025 (the 2025 Notes) and $25.0 million minimum liquidity covenant under the Company's senior secured term loan due 2028. Taking into account the repayment of the 2025 Notes and the minimum liquidity covenant, Karyopharm expects its cash, cash equivalents and investments will be sufficient to fund its operations into the fourth quarter of 2025. Full Year and Fourth Quarter 2024 Financial Results Total revenue: Total revenue for the fourth quarter of 2024 was $30.5 million, compared to $33.7 million for the fourth quarter of 2023. Total revenue for the year ended December 31, 2024 was $145.2 million, compared to $146.0 million for the year ended December 31, 2023. Net product revenue: Net product revenue for the fourth quarter of 2024 was $29.3 million, compared to $25.1 million for the fourth quarter of 2023. Net product revenue for the year ended December 31, 2024 was $112.8 million, compared to $112.0 million for the year ended December 31, 2023. License and other revenue: License and other revenue for the fourth quarter of 2024 was $1.3 million, compared to $8.7 million for the fourth quarter of 2023. License and other revenue for the year ended December 31, 2024 was $32.4 million, compared to $34.0 million for the year ended December 31, 2023. Cost of sales: Cost of sales for the fourth quarter of 2024 was $1.3 million, compared to $1.5 million for the fourth quarter of 2023. Cost of sales for the year ended December 31, 2024 was $6.0 million, compared to $4.9 million for the year ended December 31, 2023. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue. R&D expenses: R&D expenses for the fourth quarter of 2024 were $33.3 million, compared to $39.4 million for the fourth quarter of 2023. R&D expenses for the year ended December 31, 2024 were $143.2 million, compared to $138.8 million for the year ended December 31, 2023. The increase in both periods was primarily due to increased clinical trial activity, partially offset by a reduction in headcount and contractors. SG&A expenses: SG&A expenses for the fourth quarter of 2024 were $27.2 million, compared to $30.7 million for the fourth quarter of 2023. SG&A expenses for the year ended December 31, 2024 were $115.4 million, compared to $131.9 million for the year ended December 31, 2023. The decrease in both periods was primarily due to a reduction in headcount and contractors as well as lower commercial-related activities in connection with cost optimization efforts. Interest income: Interest income for the fourth quarter of 2024 was $1.5 million, compared to $2.5 million for the fourth quarter of 2023. Interest income for the year ended December 31, 2024 was $7.4 million compared to $10.9 million for the year ended December 31, 2023, due to lower investment balances in 2024 as compared to 2023. Interest expense: Interest expense for the fourth quarter of 2024 was $11.2 million, compared to $6.2 million for the fourth quarter of 2023. Interest expense for the year ended December 31, 2024 was $37.4 million, compared to $23.8 million for the year ended December 31, 2023. The increase in both periods was primarily due to the term loan and convertible debt that were issued in 2024. Gain on extinguishment of debt and other income: Other income for the fourth quarter of 2024 was $10.1 million due to non-cash fair value remeasurements. The Company had immaterial other expense in the fourth quarter of 2023. Gain on extinguishment of debt and other income for the year ended December 31, 2024 was $73.1 million primarily due to the recognition of a $44.7 million non-cash gain on extinguishment of debt and $28.7 million non-cash fair value remeasurements, both of which related to the refinancing transactions that were completed in mid-2024. The Company had immaterial other expense for the year ended December 31, 2023. Net loss: Karyopharm reported a net loss of $30.8 million, or $0.24 per basic and diluted share, for the fourth quarter of 2024, compared to a net loss of $41.8 million, or $0.36 per basic and diluted share, for the fourth quarter of 2023. Net loss included non-cash stock-based compensation expense of $3.9 million and $5.2 million for the fourth quarters of 2024 and 2023, respectively. Karyopharm reported a net loss of $76.4 million, or $0.63 per basic share and $0.93 per diluted share, for the year ended December 31, 2024, compared to a net loss of $143.1 million, or $1.25 per basic and diluted share, for the year ended December 31, 2023. Net loss included non-cash stock-based compensation expense of $18.4 million and $21.7 million for the years ended December 31, 2024 and 2023, respectively. Cash position: Cash, cash equivalents, restricted cash and investments as of December 31, 2024 totaled $109.1 million, compared to $192.4 million as of December 31, 2023. Conference Call Information Karyopharm will host a conference call today, February 19, 2025, at 8:00 a.m. Eastern Time, to discuss the fourth quarter and full year 2024 financial results, the financial outlook for 2025 and to provide other business updates. 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 XPOVIO® (selinexor) XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds 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 patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in 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 endometrial cancer and myelofibrosis. 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). For the treatment of adult patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). SELECT IMPORTANT SAFETY INFORMATION Warnings and Precautions Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care. Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors. Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care. Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care. Serious Infection: Monitor for infection and treat promptly. Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes. Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception. Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract. Adverse Reactions The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%. The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients. Use In Specific Populations Lactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit . 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 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 a growing number of ex-U.S. territories and countries, including Europe and 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 , 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 Karyopharm's guidance on its 2025 total revenue, 2025 U.S. net product revenue and 2025 R&D and SG&A expenses; expected cash runway; expectations with respect to commercialization efforts; the ability of selinexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, diffuse large B-cell lymphoma and other diseases; and expectations with respect to the clinical development plans and potential regulatory submissions of selinexor. 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; the direct or indirect impact of the COVID-19 pandemic or any future pandemic on Karyopharm's business, results of operations and financial condition; 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 September 30, 2024, which was filed with the Securities and Exchange Commission (SEC) on November 5, 2024, 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. SOURCE Karyopharm Therapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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D07073	-	D07AB19 H02AB02 D10AA03 A01AC02 S02BA06 D07XB05 S03BA01 S01CB01 C05AA09 S01BA01 R01AD03	-

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