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Nurix Therapeutics Outlines 2026 Goals and Objectives for Advancing Bexobrutideg and Its Pipeline of Novel Degrader-Based Medicines in Cancer and Autoimmune Diseases

On January 12, 2026 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines in oncology and autoimmune diseases, reported the Company’s achievements in 2025 and outlined key objectives and anticipated milestones for 2026, which will be the subject of Nurix’s corporate update at the 44th Annual J.P. Morgan Healthcare Conference today at 4:30 p.m. PT, in San Francisco.

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"2025 was a defining year for Nurix, having advanced our potentially best-in-class BTK degrader, bexobrutideg, into pivotal development for patients with relapsed or refractory CLL," said Arthur T. Sands, president and chief executive officer of Nurix. "As we enter 2026, we are focused on executing the DAYBreak CLL-201 study and initiating the confirmatory Phase 3 trial, DAYBreak CLL-306. We are also excited to advance our pipeline of wholly owned and partnered programs in inflammation and autoimmune diseases, including our new tablet formulation of bexobrutideg, our IRAK4 degrader program partnered with Gilead, and our STAT6 degrader program partnered with Sanofi. With our pivotal DAYBreak program underway, a strong balance sheet, and multiple catalysts across oncology and immunology, we believe Nurix is exceptionally well positioned to make 2026 a transformative year for the Company and the field of targeted protein degradation."

2025 Select Accomplishments and Business Highlights

Potential Best-in-Class BTK degrader, Bexobrutideg, in CLL

Presented new and updated clinical and preclinical data supporting a potential best-in-class BTK degrader profile. New and updated clinical data were presented in December 2025 at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH2025) that provide a maturing clinical picture of bexobrutideg’s efficacy, durability, and tolerability. Highlights included an 83% objective response rate, including two complete responses (4.3%) in CLL patients with a median of four prior lines of treatment. Responses were durable and deepened over time with a median progression-free survival estimated at 22.1 months, which is highly competitive with currently approved agents in a similar line of therapy. Bexobrutideg was well tolerated with no dose-limiting toxicities across all doses tested. New preclinical data were presented in October 2025 that support bexobrutideg’s potential best-in-class BTK degrader profile, demonstrating superior degradation potency, broad coverage of clinically relevant BTK mutations, and exquisite selectivity. These findings strengthen the Company’s conviction that bexobrutideg may prove to be a clinically superior medicine for the treatment of patients with CLL and other B-cell driven diseases.

Successfully addressed FDA’s Project Optimus with the selection of the 600 mg once daily dose for pivotal development in r/r CLL. The selection of the 600 mg dose was supported by data from a randomized cohort within the Phase 1b study comparing 200 mg and 600 mg in accordance with Project Optimus and reflects alignment with global regulators, including the U.S. Food and Drug Administration, the UK Medicines and Healthcare products Regulatory Agency, and the European Medicines Agency. The results, subsequently reported at ASH (Free ASH Whitepaper)2025, demonstrated a trend toward a higher objective response rate and longer progression-free survival with the 600 mg dose without an increase in adverse events. The clearance by regulators of the 600 mg dose allows Nurix to optimize bexobrutideg’s therapeutic effect, providing patients the opportunity to regain control of CLL that has progressed or has failed to respond to other therapies.

Initiated pivotal clinical development in patients with relapsed or refractory CLL. In October 2025, Nurix initiated enrollment in the DAYBreak CLL-201 pivotal Phase 2 study (NCT07221500). This single-arm, global study is evaluating bexobrutideg at 600 mg once daily in patients with relapsed or refractory CLL whose disease progressed following treatment with a BTK inhibitor and a BCL2 inhibitor. The trial is designed to support accelerated approval of bexobrutideg in triple-exposed CLL/SLL patients. Nurix plans to initiate a randomized confirmatory Phase 3 trial in 2026 to support full approval of bexobrutideg.

First-in-class CBL-B Inhibitor NX-1607

Presented positive Phase 1a clinical data demonstrating immune activation and clinical activity. New Phase 1a clinical data for NX-1607 were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in October and the 2025 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November, demonstrating dose-dependent pharmacologic activity and signals of clinical activity across a diverse set of 82 patients with eleven different tumor types. Clinical activity was observed through reductions in tumor-specific biomarkers such as prostate-specific antigen (PSA) in prostate cancer and carcinoembryonic antigen (CEA) in colorectal cancer. Notably, there was a confirmed partial response in a patient with micro-satellite stable colorectal cancer (MSS CRC), a tumor type typically unresponsive to immune checkpoint therapy. As anticipated, treatment with NX-1607 led to increased peripheral T cell activation and proliferation, indicating active T-cell receptor engagement and immune responsiveness, suggesting its potential as an active immune-oncology agent with a unique mechanism distinct from PD-1/PD-L1 therapies.

Advancing Pipeline in Inflammation and Autoimmune Diseases

Introduced new tablet formulation of bexobrutideg into Phase 1 testing to support an IND for inflammation and autoimmune indications. In 2025, Nurix initiated a Phase 1 single ascending and multiple ascending dose (SAD/MAD) study to evaluate pharmacokinetics (PK), pharmacodynamics (PD), and safety of a new tablet formulation of bexobrutideg. This study is intended to support an IND filing and enable expansion into inflammatory and autoimmune indications beginning in 2026.

Partner Gilead initiated Phase 1 testing of IRAK-4 degrader. In April 2025, Nurix announced that the FDA cleared the Investigational New Drug (IND) application for GS-6791 (previously NX-0479), a novel, potentially best-in-class oral degrader of IRAK4 being developed in collaboration with Gilead Sciences. GS-6791 is designed to selectively degrade IRAK4, a key signaling protein that drives inflammation in autoimmune and inflammatory diseases. Gilead subsequently initiated an ongoing Phase 1 trial in healthy volunteers, the results of which will inform Nurix’s option for a 50/50 co-development and U.S. profit share.

Partner Sanofi advanced STAT6 degrader program into IND enabling studies: In June 2025, Nurix announced that Sanofi exercised its option to extend its license for Nurix’s STAT6 program, including the development candidate NX-3911. NX-3911 is an oral, highly selective degrader of STAT6, a key transcription factor within the IL-4/IL-13 signaling pathways that drive inflammation in allergic and type 2 inflammatory conditions, which currently is in IND enabling studies. Sanofi is responsible for all development activities, and Nurix retains an option for a 50/50 U.S. profit share and co-promotion after initial clinical proof of concept.

Corporate and Leadership

Strengthened financial position to support execution of bexobrutideg pivotal program and expansion into inflammation and autoimmune disease. In October 2025, Nurix closed an underwritten registered offering of 24,485,799 shares of its common stock, providing gross proceeds to Nurix of $250.0 million, before deducting underwriting discounts and commissions and other offering expenses payable by Nurix. In addition, Nurix earned $47.0 million in non-dilutive capital through its strategic collaborations with Gilead, Sanofi and Pfizer. Nurix is well capitalized with pro forma cash/investments of $663.8 million1.

Strengthened leadership with appointments of chief commercial officer and new board members with deep experience in drug development and commercialization. In 2025, Nurix announced the hiring of John Northcott as chief commercial officer, bringing extensive U.S. and global commercial leadership experience, including both pre-launch planning and on-market commercialization in hematology, oncology and a wide range of other therapeutic areas. In addition Nurix also appointed two board members: Roy Baynes, MB.Bch., M.Med., Ph.D., who has extensive experience in the development of innovative, blockbuster medicines during a distinguished career in hematology and oncology, and Roger Dansey, M.D., senior leader in drug development and operations with over 25 years of executive experience in pharmaceutical and biotech companies across both U.S. and international markets.

2026 Outlook: Executing the Next Phase of Growth

Execute pivotal development pathway in CLL:
Enrollment of pivotal Phase 2 trial – DAYBreak CLL-201
Initiation of a confirmatory Phase 3 study in patients with r/r CLL in the 2L+ setting comparing bexobrutideg monotherapy to pirtobrutinib – DAYBreak CLL-306
Initiation of a Phase 1b/2 clinical study in patients with CLL in combination with other therapeutic agents including venetoclax (BCL-2 inhibitor)
Advance Degrader Programs in I&I:
Bexobrutideg – data from new tablet formulation SAD/MAD study supporting IND in I&I
GS-6791 IRAK4 degrader – potential Phase 1 results2
NX-3911 STAT6 degrader – potential IND filing by Sanofi2
Report Ongoing Clinical Data Updates:
Bexobrutideg Phase 1a/b CLL cohorts
Bexobrutideg Phase 1a/b NHL cohorts
Zelebrudomide Phase 1a cohorts
Progress Research and Development Pipeline:
Leverage DEL-AITM platform to fuel wholly owned and partnered drug discovery programs
Earn additional research milestones and potential licensing fees from its collaborations with Gilead, Sanofi, and Pfizer.

1Represents cash balance as of August 31, 2025, plus the net proceeds from the October 2025 registered direct offering

2Statements include Nurix estimate for partnered programs using industry standard timelines based on current stage of development (not official guidance of partners).

About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, highly selective small molecule degrader of BTK currently being evaluated in the DAYBreak CLL-201 clinical trial (NCT07221500), a pivotal single-arm Phase 2 study of bexobrutideg in patients with relapsed or refractory chronic lymphocytic leukemia. Bexobrutideg also continues to be studied in the NX-5948-301 Phase 1a/1b clinical trial (NCT05131022) in patients with relapsed or refractory B cell malignancies.

About NX-1607
NX-1607 is an investigational first-in-class oral inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) being developed for immuno-oncology indications, including a range of solid tumor types. CBL-B is a cytoplasmic E3 ubiquitin ligase that negatively regulates T cell activation, making it an attractive target for immuno-oncology and offering a novel therapeutic approach to treat solid tumors. Inhibition of CBL-B in preclinical studies reverses T cell exhaustion, alleviates tumor induced immunosuppression, and may also exert direct antitumor effects. Nurix is evaluating NX-1607 in an ongoing Phase 1 trial in adults in a range of oncology indications. This study includes a thorough investigation of both dose and schedule in the Phase 1a portion. Additional information on the NX-1607 clinical trial can be accessed at www.clinicaltrials.gov (NCT05107674).

(Press release, Nurix Therapeutics, JAN 12, 2026, View Source [SID1234661962])

Nerviano Medical Sciences announces NMPA Clearance of IND for PARP7-Selective Inhibitor Atamparib in Promising New Therapeutic Setting

On January 12, 2026 NMS Group (NMS), a global leader in oncological innovation, reported that the China’s National Medical Products Administration (NMPA) has granted approval to the Investigational New Drug (IND) application for its first-in-class, orally bioavailable PARP7-selective inhibitor, atamparib, enabling its clinical studies in patients with advanced solid tumors.

The phase Ib/II clinical trial expected to start in the first quarter of 2026 is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of atamparib in patients with advanced solid tumors, with a focus on a promising new therapeutic sub-setting. The goal is to validate the molecule’s differentiated mechanism of action and its favorable safety and tolerability with more than 200 patients treated so far, both in late-line patients and in future combination with standard-of-care in earlier treatment settings.

"The IND approval in China represents a key strategic milestone for the development of atamparib," said Hugues Dolgos, CEO of NMS Srl. "Recent data generated across preclinical and clinical programs, along with the newly published mechanism of action, have enabled us to reposition this asset into a promising sizeable indication where we believe it can deliver meaningful clinical benefit."

"Conducting the study in China is expected to support atamparib global clinical development by enabling timely access to a clinically relevant patient population and facilitating the potential availability of new treatment options for patients in China and worldwide," said Dadong Li, CEO of NMS Shanghai. "This milestone marks an important step in advancing the development of atamparib and exploring its potential to expand treatment options for patients."

In parallel, NMS is advancing a dual inhibitor program currently in preclinical development, targeting PARP7 and another undisclosed target, which is expected to complement the clinical development strategy of atamparib and underscores the company’s commitment to building a differentiated portfolio of innovative therapeutic candidates.

(Press release, Nerviano Medical Sciences, JAN 12, 2026, View Source [SID1234661961])

Mereo BioPharma Provides Corporate Update

On January 12, 2026 Mereo BioPharma Group plc (NASDAQ: MREO) ("Mereo" or the "Company"), a clinical-stage biopharmaceutical company focused on rare diseases, reported an update on its programs, setrusumab for the treatment of osteogenesis imperfecta (OI) and alvelestat, which is being studied for the treatment of alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD), and revised its cash runway guidance.

Data from the Phase 3 Orbit and Cosmic studies of setrusumab in osteogenesis imperfecta, including data on bone mineral density, vertebral fractures, and patient reported outcomes on pain and physical function, will be presented at the J.P. Morgan Healthcare Conference.

The Company is also updating its previous cash runway guidance. As of December 31, 2025, cash and cash equivalents were approximately $41 million, which are expected to fund operations to mid-2027.

"The reductions and delays in pre-commercial and manufacturing activities related to setrusumab that we implemented following the recent top-line data from the Phase 3 Orbit and Cosmic studies have extended our cash runway to mid-2027 and we will continue to tightly manage our resources as we assess potential next steps for the program, alongside our partner, Ultragenyx," said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo. "There are no FDA or EMA approved treatments for people living with OI. Although bisphosphonates are used to improve bone mineral density, OI remains a high unmet need. We will continue to assess the totality of the Phase 3 trial data to determine next steps, including potential interactions with the regulators. In parallel, we are advancing partnering discussions for our Phase 3 ready program, alvelestat in AATD-LD."

Dr. Scots-Knight is scheduled to present at the 44th Annual J.P. Morgan Healthcare Conference on Wednesday, January 14, 2026 at 1:30pm PT (9:30pm GMT). A live audio webcast of the presentation can be accessed through the news and events section of the Company’s website at www.mereobiopharma.com/news. Following the conclusion of the live event, an archived replay will be available on the Company’s website.

Setrusumab (UX143)

As announced on December 29, 2025, the Phase 3 Orbit and Cosmic studies of setrusumab in OI did not achieve statistical significance against the primary endpoints of reduction in annualized clinical fracture rate compared to placebo or bisphosphonates, respectively. Both studies achieved strong statistical significance against the key secondary endpoint of improvement in bone mineral density versus comparator. The improvement in bone mineral density in the Cosmic study was associated with a decreased rate of fracture in this younger more highly fracturing patient population, although this was not statistically significant. The safety profile of setrusumab was consistent with that observed in prior studies.

Further analyses of the data from both studies are ongoing to determine the path forward, including potential regulatory interactions.

There is a high unmet medical need in OI, which is associated with a substantial clinical, humanistic and economic burden of illness due to the complexity of the condition and necessary medical care and support. As well as fractures, people living with OI present with a broad spectrum of skeletal features including bone deformity, scoliosis and growth impairment. Pain is the most common and impactful sign, symptom or clinical event reported in children and adolescents.

There are no EMA or FDA approved treatments for OI (except for neridronate, which is approved nationally in Italy). Bisphosphonates are used off-label in children in Europe and the U.S., despite the lack of clinical evidence to support their effectiveness in reducing fractures.

Alvelestat (MPH-966)

The Company is continuing to advance key activities to support the planned initiation of the global Phase 3 pivotal study. Based on previous discussions with the FDA and EMA, Mereo anticipates a single Phase 3 trial enrolling approximately 220 early- and late-stage AATD-LD patients evaluating alvelestat over an 18-month treatment period will support regulatory submissions in both the U.S. and Europe. The primary efficacy endpoint for U.S. approval will be the St. George’s Respiratory Questionnaire (SGRQ) Total Score, with lung density measured by CT scan serving as the primary endpoint for potential European regulatory approval.

Mereo continues to be in active discussions with potential partners for the Phase 3 development and commercialization of alvelestat.

Vantictumab (OMP18R5)

The Company out-licensed vantictumab for autosomal dominant osteopetrosis Type 2 (ADO2) to āshibio, Inc. whilst retaining European rights. āshibio, Inc. is responsible for funding the global program and following regulatory discussions, plans to initiate a Phase 2 study in 2H 2026. Vantictumab was previously investigated in Phase 1a/b oncology trials in around 100 patients with biomarker evidence of potential impact on osteoclast function and high bone turnover which led to fragility fractures in some patients. āshibio, Inc. reported promising pre-clinical data at ASBMR 2025 in ADO2 mouse model. Vantictumab significantly decreased areal bone mineral density and rescued the bone phenotype in the ADO2 mouse model.

(Press release, Mereo BioPharma, JAN 12, 2026, View Source [SID1234661958])

New Data Underscoring Ability of Leapfrog Bio’s OncoSLX Platform to Identify Drug Retargeting Opportunities for Treating Cancer Published in Nature Portfolio Journal

On January 12, 2026 Leapfrog Bio, a clinical-stage precision oncology company dedicated to discovering and developing novel targeted therapies for cancers caused by loss-of-function (LOF) mutations, reported the publication of a peer‑reviewed study in npj Systems Biology and Applications, a Nature Portfolio journal, titled "Challenges and opportunities for oncology drug repurposing informed by synthetic lethality." The paper provides a practical framework for drug retargeting in oncology and highlights core discoveries that helped guide the optimization of Leapfrog Bio’s OncoSLX Platform.

"This paper validates two fundamental realities in targeted cancer drug discovery: genetic targeting opportunities discovered in cell lines are more likely to hold up in the clinic when caused by a driver mutation, and drugs behave very differently from genetic knockouts, so screening them against the causal biology is essential," said Tomas Babak, Ph.D., Founder and Chief Scientific Officer of Leapfrog Bio and co-author on the publication. "Our OncoSLX platform is built on these principles and allows us to run thousands of these drug-mutation tests against all cancer driver mutations simultaneously, quickly identifying potent, genetically targeted treatments for LOF cancers."

Dr. Babak continued, "By screening clinically safe drugs, we can restart development in Phase 2 in genetically selected patients where the probability of efficacy is higher. We expect this approach to be significantly accelerating and derisking as we advance through development."

"Leapfrog Bio was founded to bring the transformative benefit of precision medicines to the many patients with cancers caused by LOF mutations, for whom targeted options are limited," said Greg Vontz, Chief Executive Officer of Leapfrog Bio. "Among our most promising discoveries to date is the vulnerability of EP300 LOF cancers to BET inhibitors, like our lead candidate, LFB190. Leveraging learnings from our OncoSLX platform, we are positioned to advance LFB190 directly into mid-stage development. We look forward to initiating our planned Phase 1b/2a trial in mid-2026."

LFB190 is an oral, small-molecule, potentially best-in-class BETi in development for the more than 60,000 U.S. patients annually who are diagnosed with EP300-mutated solid tumors, including non-small cell lung, bladder, colon, pancreatic, head and neck, and bile duct cancers. While BET inhibitors have been widely studied across cancer indications, they have shown limited efficacy in genetically unselected populations. Extensive preclinical studies have shown that BET inhibitors can be highly effective when used to treat EP300-driven cancers, and previous clinical development of LFB190 as an untargeted therapy has shown favorable safety and tolerability for the drug.

About OncoSLX Platform
OncoSLX Platform is Leapfrog Bio’s proprietary pharmacogenetic platform that screens clinically characterized small molecules against isogenic models of cancer driver mutations, focusing on loss‑of‑function biology. Unlike traditional synthetic‑lethality approaches based on gene knockouts, OncoSLX captures the full spectrum of drug biology and then integrates real‑world outcomes data to prioritize indications likely to deliver survival benefit, compressing timelines and reducing translational risk. This approach identifies novel treatments for loss-of-function-driven cancers that cannot be discovered by conventional methods.

About LFB190 and EP300-Mutated Cancers
LFB190 is a novel, oral BET inhibitor for the treatment of solid tumors driven by EP300 loss-of-function (LOF) mutations. Leapfrog Bio’s OncoSLX Platform has identified a novel synthetic lethality relationship between BET inhibitors and EP300 LOF mutations, which are a known and frequent cancer driver with no targeted therapy available. LFB190 has shown strong preclinical efficacy in patient-derived xenograft (PDX) models of EP300-mutated cancers. EP300 is a tumor suppressor gene involved in chromatin remodeling and transcriptional regulation. When mutated, its loss contributes to tumor progression across multiple cancer types, including approximately 6 percent of non-small cell lung cancers (NSCLC), approximately 15 percent of bladder cancers, and similar frequencies in colon, pancreatic, and head and neck cancers. While BET inhibitors have historically shown limited efficacy in unselected populations, Leapfrog Bio’s platform revealed a compelling effect in EP300-mutated tumors.

(Press release, Leapfrog Bio, JAN 12, 2026, View Source [SID1234661957])

Karyopharm Announces Preliminary Unaudited 2025 Revenue and Reiterates Expectation of Delivering Potentially Transformative Phase 3 Data in 2026

On January 12, 2026 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported preliminary unaudited fourth quarter and full year 2025 total revenue and U.S. XPOVIO net product revenue estimates and outlined its 2025 achievements and 2026 objectives.

"2026 has the promise to be a transformative year for Karyopharm and the patient communities that we intend to serve, with top-line data from our Phase 3 SENTRY trial in myelofibrosis expected in March. Positive data from our SENTRY trial could unlock our opportunity to improve patient outcomes and redefine the standard-of-care in myelofibrosis. Our teams are actively preparing for regulatory filings, commercialization and the opportunity to rapidly launch with the first ever combination therapy in a multi-billion dollar market," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "In endometrial cancer, we remain focused and on track to report top-line data from our Phase 3 XPORT-EC-042 trial in mid-2026, representing a significant opportunity to transform patient outcomes in a targeted, biomarker driven patient population. With two high-potential data readouts this year, 2026 is expected to be a catalyst-rich year that could position us for tremendous long-term value creation."

Key Program Highlights in 2025

Selinexor in Multiple Myeloma

Demand for XPOVIO was consistent in 2025 versus 2024 in the increasingly competitive multiple myeloma marketplace, with the community setting continuing to drive approximately 60% of overall net product revenue.

Global patient access for selinexor expanded in 2025, with favorable reimbursement decisions in Spain and China, and additional regulatory approvals in multiple countries where selinexor is now approved in more than 50 countries.
Selinexor in Myelofibrosis

Completed enrollment of the Phase 3 SENTRY trial (XPORT-MF-034; NCT04562389) with 353 patients in early September 2025. SENTRY is evaluating 60 mg once-weekly selinexor in combination with ruxolitinib compared to ruxolitinib plus placebo. The preliminary baseline characteristics for patients enrolled in SENTRY as presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2025 Annual Meeting (n=320) are representative of the intended patient population. In addition, preliminary blinded aggregate safety data from the first 61 patients with a median follow-up of greater than 12 months may suggest improvements in both hematologic and non-hematologic treatment emergent adverse events as compared to the Phase 1 data evaluating selinexor 60 mg weekly in combination with standard of care ruxolitinib in JAKi-naïve myelofibrosis patients, as well as historical ruxolitinib monotherapy data. The Company cautions that preliminary baseline characteristics and preliminary blinded aggregate safety data from the Phase 3 SENTRY trial may not ultimately be reflective of the actual trial results.

Presented data from the XPORT-MF-035 (NCT04562870) Phase 2, randomized, open-label trial of selinexor versus physician’s-choice in hard-to-treat patients with heavily pretreated myelofibrosis (n=24) at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress. The data suggest the potential for single-agent clinical activity with selinexor, including spleen volume reduction, symptom improvement, hemoglobin stabilization, reduced transfusion burden, and evidence of disease modification.
Selinexor in Endometrial Cancer

Modified the design of the Phase 3 XPORT-EC-042 (NCT05611931) trial to: a) focus enrollment on patients with either: i) proficient mismatch repair status (pMMR) tumors; or ii) patients with deficient mismatch repair status (dMMR) tumors who are medically ineligible for checkpoint inhibitors; b) introduce a new modified intent-to-treat (ITT) population of approximately 220 patients comprised of this focused population; and, c) increase the ITT sample size to approximately 276 patients.

Enrollment continues in the 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.
Corporate and Financial Highlights for 2025

Based on preliminary unaudited financial information, the Company expects total revenue, which includes license and royalty revenue from partners, to be approximately $33 million for the fourth quarter 2025 and approximately $145 million for the full year 2025, and U.S. XPOVIO net product revenue to be approximately $32 million for the fourth quarter 2025 and approximately $115 million for the full year 2025.

Completed strategic financing transactions that extended cash runway beyond the expected top-line readout of the Phase 3 SENTRY trial in myelofibrosis.

Cash, cash equivalents, restricted cash and investments as of December 31, 2025 were approximately $64 million. The Company expects its existing liquidity, including the revenue it expects to generate from XPOVIO net product sales and its license agreements, will be sufficient to fund its planned operations into the second quarter of 2026.
The financial information presented in this press release may be adjusted as a result of the completion of customary annual review and audit procedures.

Anticipated Catalysts and Operational Objectives in 2026

Myelofibrosis

Top-line data from the Phase 3 SENTRY trial is expected in March 2026.

The Company expects to report top-line data from all patients in the 60 mg cohort of the Phase 2 SENTRY-2 trial with at least 24 weeks of follow-up in the second half of 2026.
Endometrial Cancer

Top-line data from the event-driven, Phase 3 XPORT-EC-042 trial is expected in mid-2026. The Company continues to enroll patients into the XPORT-EC-042 trial of selinexor as a maintenance monotherapy for patients with TP53 wild-type advanced or recurrent endometrial cancer.
Multiple Myeloma

Maintain the Company’s commercial foundation in the increasingly competitive multiple myeloma marketplace and drive increased XPOVIO revenues.

Continue to support global launches by our partners following regulatory and reimbursement approvals for selinexor in ex-U.S. territories.

Continue to follow patients that are enrolled in the Phase 3 XPORT-MM-031 (EMN29) trial. The Company expects to report top-line data from this event-driven trial in the second half of 2026.
Corporate Presentation

Karyopharm will be posting an updated corporate overview presentation on its website today. The presentation will be accessible under "Events & Presentations" in the Investor section of the Company’s website, View Source

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 are randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline.

About Myelofibrosis

Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union1. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib. Patients treated with the most commonly prescribed JAK inhibitor often require blood transfusions, and more than 30% will discontinue treatment due to anemia.2 Anemia and transfusion dependence are correlated with poor prognosis and shortened survival.3

1. Clarivate/DRG (2023)
2. Palandri, F., Palumbo, G.A., Elli, E.M. et al. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis. Blood Cancer J. 11, 4 (2021).
3. Pardanani, A., & Tefferi, A. (2011). Prognostic relevance of anemia and transfusion dependency in myelodysplastic syndromes and primary myelofibrosis. Haematologica, 96(1), 8–10.

About the Phase 3 XPORT-EC-042 Trial

EC-042 (XPORT-EC-042; NCT05611931) is a global, Phase 3, randomized, double-blind clinical trial evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. The EC-042 trial is expected to enroll approximately 276 patients who will be randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The trial includes two patient populations, for which, the primary endpoint of progression free survival will be tested sequentially and the key secondary endpoint of overall survival will be evaluated: 1) a modified intent to treat population (mITT) that will include patients with either, a) TP53 wild-type tumors with proficient mismatch repair status (pMMR); or, b) TP53 wild-type tumors with deficient mismatch repair status (dMMR), who are medically ineligible to receive checkpoint inhibitors; and, 2) 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 mITT population is expected to include approximately 220 patients. In connection with the EC-042 trial, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOneCDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type.

About Endometrial Cancer

Endometrial cancer (EC) is the most common gynecologic malignancy in the U.S.1 In 2025, approximately 69,120 uterine cancers (predominantly endometrial) are expected to be diagnosed, with 13,860 deaths.1 In 2022, there were about 420,368 cases with 97,723 deaths worldwide.2 Both incidence and mortality have continued to rise.3,4 Key risk factors include obesity, type 2 diabetes, high-fat diets, tamoxifen or oral estrogen use, and delayed menopause.5 TP53 is a well-recognized prognostic marker for EC; >50% of advanced or recurrent EC tumors are TP53wt (gene for tumor protein P53; wild-type), and ~40%-55% are both TP53wt and mismatch repair-proficient (pMMR).6-8 While immune checkpoint inhibitors have shown benefit in patients with mismatch repair–deficient (dMMR) and pMMR, the magnitude of benefit is greater for patients with dMMR tumors versus pMMR tumors.9-10 There remains an unmet need for targeted therapies for patients with pMMR EC.

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 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: [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 www.XPOVIO.com.

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

(Press release, Karyopharm, JAN 12, 2026, View Source [SID1234661956])