On November 3, 2025 Recordati Rare Diseases Inc. reported the presentation of new data related to its growing portfolio of treatments for rare hematologic disorders at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which takes place December 6-9, 2025, in Orlando, Fla. In a series of nine poster presentations, Recordati researchers and independent investigators will present research detailing advances in Castleman disease (CD), cold agglutinin disease (CAD)/cold agglutinin syndrome (CAS), and immune-related complications of CAR T-cell therapy. Highlights include a report on the development of an artificial intelligence (AI) model that evaluates CD tissue samples; an analysis of the morbidity burden and healthcare costs among patients with idiopathic multicentric Castleman disease (iMCD); the first real-world evaluation of sutimlimab in the treatment of patients with CAD or CAS; and a prospective evaluation of siltuximab in the prevention or treatment of cytokine release syndrome (CRS) after CAR T-cell therapy.

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"We are particularly excited about the long-term safety data for sutimlimab in cold agglutinin disease and the growing body of research investigating the use of siltuximab in Castleman disease," said Milan Zdravkovic, Executive Vice President, Research & Development and Chief Medical Officer at Recordati. "Also notable is the poster describing an innovative, AI-based approach to lymph node analysis, which could represent a meaningful step toward earlier and more consistent diagnosis of Castleman disease, one of the most difficult hematologic conditions to diagnose accurately. Altogether, the datasets presented at ASH (Free ASH Whitepaper) 2025 reflect Recordati’s ongoing commitment to advancing care for people living with rare hematologic disorders."

"The ASH (Free ASH Whitepaper) Annual Meeting is an important opportunity to showcase research advances in hematologic diseases, and we are pleased that the meeting organizers have accepted nine abstracts related to our therapies," said Mohamed Ladha, President and General Manager at Recordati Rare Diseases North America. "Together with our independent research partners, Recordati is at the forefront of advancing potential therapeutic solutions for people living with devastating conditions such as Castleman disease. We look forward to these data sparking further dialogue and collaboration as we continue in our efforts to improve patients’ lives."

The ASH (Free ASH Whitepaper) 2025 Annual Meeting will feature the following poster presentations:

Castleman Disease

Poster number: 2606
Title: Retrospective real-world data analysis of morbidity burden and healthcare costs in idiopathic multicentric Castleman disease compared with matched controls (BURDEN-iMCD)
Presenting author: Sudipto Mukherjee, MD, PhD, MPH, Cleveland Clinic

Poster number: 3001
Title: Comprehensive analysis of subtype-specific outcomes and management in Castleman disease: a 20-year cohort study
Presenting author: Yoshito Nishimura, MD, PhD, MPH, Mayo Clinic

Poster number: 3002
Title: Automated grading of Castleman disease histopathology using an attention-based multiple-instance learning model
Presenting author: Muir Morrison, PhD, University of Utah

Poster number: 3009
Title: Pediatric idiopathic multicentric Castleman disease is often severe and responds to siltuximab
Presenting author: Bridget Austin, MS, Perelman School of Medicine, University of Pennsylvania, Center for Cytokine Storm Treatment & Laboratory

Poster number: 3006
Title: Epidemiology and clinical characteristics of idiopathic multicentric Castleman disease in Spain (ARCANA study): Prevalence cohort
Presenting author: José-Tomás Navarro, MD, PhD, Catalan Institute of Oncology, Josep Carreras Leukaemia Research Institute

Poster number: 4788
Title: Siltuximab-mediated suppression of CRP is associated with clinical response in idiopathic multicentric Castleman disease
Presenting author: Jean-Francois Rossi, MD, PhD, Université de Montpellier

Cold Agglutinin Disease (CAD)

Poster number: 6242
Title: Real-world safety of sutimlimab in patients with CAD/CAS: a multinational, multicenter, observational, prospective cohort study
Presenting author: Alexander Röth, MD, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen

CAR T-Cell Therapy Toxicity (including in B-Cell Lymphoma)*

Poster number: 2385
Title: Safety and immunomodulatory effects of siltuximab prophylaxis prior to standard of care CD19 directed chimeric antigen receptor T-cell (CD19.CART) therapy for B-cell lymphomas: final Phase I trial results
Presenting author: Nathan Denlinger, DO, MS, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center

Poster number: 5919
Title: Siltuximab versus tocilizumab for the management of CAR T-cell associated cytokine release syndrome
Presenting author: Mayur Narkhede, MD, University of Alabama at Birmingham

*These studies were conducted as investigator-sponsored studies without research involvement by Recordati.

About Idiopathic Multicentric Castleman Disease (iMCD)
Idiopathic multicentric Castleman disease is a rare cytokine-driven disorder that may be life-threatening and can affect people of any age. Its symptoms often resemble those of malignant lymphoma, autoimmune, or infectious diseases, making it difficult to diagnose. iMCD is a subtype of Castleman disease (CD), which is a group of rare conditions that affect the immune system, characterized by swollen lymph nodes and a broad range of inflammatory signs and symptoms. The cause of iMCD is unknown, and there are no known risk factors. Some people with iMCD have elevated levels of interleukin 6 (IL-6), a cytokine that is produced in the body during inflammation and which plays a central pathological role in iMCD; IL-6 elevation may explain some of the symptoms patients experience, such as swollen lymph nodes, fever, unexplained weight loss, and night sweats.

About Cold Agglutinin Disease (CAD)
Cold agglutinin disease (CAD) is a rare type of autoimmune hemolytic anemia (AIHA), characterized as a low-grade lymphoproliferative disorder of the bone marrow. In CAD, autoantibodies bind to erythrocytes at temperatures ≤37°C, leading to complement-mediated hemolysis. CAD symptoms include severe, debilitating fatigue and other clinical manifestations (e.g., dyspnea, tachycardia) that can impact patients’ quality of life. While the median age of onset is approximately 60 years, CAD has been diagnosed in patients as young as 30.

(Press release, Recordati, NOV 3, 2025, View Source [SID1234659296])

On November 3, 2025 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported the acceptance of two abstracts for poster presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2025 annual meeting taking place from December 6 to 9, 2025, in Orlando, FL.

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First poster – Development update on eti-cel

The first poster provides a development update on eti-cel product candidate (UCART20x22), an allogeneic dual CAR-T targeting CD20 and CD22 being developed in Phase 1 of the NATHALI-01 clinical trial, for patients with relapsed/refractory non Hodgkin lymphoma (r/r NHL). In addition, the poster outlines the addition of low dose interleukin-2 (IL-2) to further deepen and extend anti-tumor activity of eti-cel in patients with r/r NHL, supported by compelling preclinical data.

Cellectis unveiled preliminary results on eti-cel, which demonstrate an encouraging overall response rate (ORR) of 86% and a complete response (CR) rate of 57% at the current dose level (n=7), with 4 out of 7 patients achieving a complete response. The preliminary high rate of complete responses underscores the potential of this innovative approach to transform outcomes for r/r NHL patients. Cellectis expects to present the full Phase 1 dataset for eti-cel, including low-dose IL-2 combination cohorts, in 2026.

"We are excited by the progress and evolution of the eti-cel program with the addition of IL-2, which promises to build on the encouraging preliminary response rates observed in the Phase 1 program," said Adrian Kilcoyne, MD, MPH, MBA, Chief Medical Officer at Cellectis. "We look forward to sharing the full Phase 1 dataset including the IL-2 cohorts expected in 2026."

Poster title: Trial in progress: Open-label dose-finding and dose-expansion study to evaluate the safety, expansion, persistence, and clinical activity of UCART20x22 in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) NATHALI-01

Presenter: Vivian Dai, Senior Director, Clinical Research Scientist at Cellectis

Date/Time: December 7, 2025 at 6:00 PM – 8:00 PM ET

Room: OCCC – West Halls B3-B4

Second poster – Correlation between alemtuzumab exposure and response with lasme-cel

The second poster highlights the correlation between alemtuzumab exposure and depth of response in the difficult-to-treat patients who have received lasme-cel (UCART22) in the course of the Phase 1 of BALLI-01, a clinical trial testing this allogeneic CAR-T product candidate targeting CD22 in relapsed/refractory acute lymphoblastic leukemia (ALL). Additionally, the data identifies a threshold exposure level of alemtuzumab above which achieving a complete response/complete response with incomplete hematologic recovery (CR/CRi) is more likely without any increase in toxicities.

"We strongly believe in the critical role of alemtuzumab in optimizing responses in these heavily pretreated patients," said Adrian Kilcoyne, MD, MPH, MBA, Chief Medical Officer at Cellectis. "These data have confirmed this and demonstrated that we could further enhance the high CR/CRi and minimal residual disease (MRD)-negative rates observed in our Phase 1 program. We look forward to starting enrollment in our pivotal Phase 2 program in Q4 2025."

Poster title: Increased alemtuzumab exposure correlates with improved responses in heavily pretreated R/R ALL patients: Analysis of the BALLI-01 trial

Presenter: Xenia Naj, Ph.D., Director Translational Sciences at Cellectis

Date/Time: December 8, 2025, 6:00 PM – 8:00 PM

Room: OCCC – West Halls B3-B4

(Press release, Cellectis, NOV 3, 2025, View Source [SID1234659247])

On November 3, 2025 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the third quarter ended September 30, 2025 and highlighted progress on key clinical development programs.

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"This has been a very productive quarter as we have strengthened our financial foundation and made meaningful clinical progress with enrollment completion of our Phase 3 SENTRY trial in myelofibrosis, marking a pivotal milestone for Karyopharm," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "With SENTRY enrollment complete, our teams remain focused on clinical trial execution, preparing for top-line data in March, potential regulatory filings, and commercial launch readiness, as we work to redefine the standard-of-care for frontline myelofibrosis patients, pending regulatory approvals."

Third Quarter 2025 Highlights

XPOVIO Commercial Performance

U.S. net product revenue was $32.0 million in the third quarter of 2025, an increase of 8.5% compared to $29.5 million in the third quarter of 2024.

Demand for XPOVIO was consistent in the third quarter of 2025 compared to the third quarter of 2024, with the community setting continuing to drive approximately 60% of overall net product revenue.

Expanded global patient access for selinexor is translating into growth in royalty revenue from the Company’s international partners, primarily the Menarini Group. Royalty revenue increased to $1.5 million in the third quarter of 2025 compared to $0.9 million in the third quarter of 2024.
Research and Development (R&D) Highlights

Myelofibrosis

The Phase 3 SENTRY trial (XPORT-MF-034; NCT04562389) completed enrollment 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 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 the preliminary baseline characteristics and preliminary blinded aggregate safety data may not ultimately be reflective of the actual trial results.

The Company continues to enroll JAKi-naïve myelofibrosis patients with platelet counts above 50,000 in the selinexor 60 mg cohort of the Phase 2 SENTRY-2 trial (XPORT-MF-044; NCT05980806). A recently amended protocol includes patients with platelet counts above 100,000. The Company expects to report top-line data from all patients in the 60 mg cohort with at least 24 weeks of follow-up in 2026.
Endometrial Cancer

Enrollment continues in the Phase 3 XPORT-EC-042 (NCT05611931) trial evaluating selinexor as a maintenance-only therapy following systemic therapy versus placebo in patients with TP53 wild-type advanced or recurrent endometrial cancer.
Multiple Myeloma

Enrollment in the Phase 3 XPORT-MM-031 trial (EMN29; NCT05028348) was completed in the fourth quarter of 2024 (n=117). The trial is being conducted in collaboration with the European Myeloma Network and is evaluating the all-oral combination of selinexor 40 mg, pomalidomide and dexamethasone (SPd40) in patients with previously treated multiple myeloma who received an anti-CD38 in their immediate prior line of therapy.
Anticipated Catalysts and Operational Objectives

Myelofibrosis

Top-line data from the Phase 3 SENTRY trial is expected in March 2026.
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 first half of 2026.
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. The Company expects to report top-line data from this event-driven trial in mid-2026.
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 $110 million to $120 million.

Lowering the range of R&D and selling, general and administrative (SG&A) expenses to $235 million to $245 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.
Third Quarter 2025 Financial Results

Total revenue: Total revenue for the third quarter of 2025 was $44.0 million, compared to $38.8 million for the third quarter of 2024.

Net product revenue: Net product revenue for the third quarter of 2025 was $32.0 million, compared to $29.5 million for the third quarter of 2024. The increase was primarily driven by gross-to-net favorability.

License and other revenue: License and other revenue for the third quarter of 2025 was $12.0 million, compared to $9.3 million for the third quarter of 2024. The increase was primarily driven by milestone-related revenue from Menarini.

Cost of sales: Cost of sales for the third quarter of 2025 was $2.1 million, compared to $1.3 million for the third quarter of 2024. Cost of sales reflects the costs of XPOVIO units sold and the costs of products sold to our partners.

R&D expenses: R&D expenses for the third quarter of 2025 were $30.5 million, compared to $36.1 million in the third quarter of 2024. The decrease was driven by lower clinical trial costs for selinexor in multiple myeloma, reflecting the reduced scope of our Phase 3 trial, and lower personnel and stock-based compensation expenses resulting from previously implemented cost-reduction initiatives.

SG&A expenses: SG&A expenses for the third quarter of 2025 were $26.6 million, compared to $27.6 million for the third quarter of 2024. The decrease was primarily driven by the realization of previously implemented cost reduction initiatives, largely offset by higher professional fees incurred during the quarter in connection with the financing transactions announced by the Company on October 8, 2025.

Loss from operations: Loss from operations for the third quarter of 2025 was $15.2 million, an improvement of approximately 42% compared to a loss of $26.3 million in the third quarter of 2024.

Interest expense: Interest expense for the third quarter of 2025 was $11.0 million, compared to $11.4 million for the third quarter of 2024.

Other (expense) income: Other expense for the third quarter of 2025 was $7.4 million compared to other income of $3.8 million for the third quarter of 2024. The change is primarily attributable to recurring non-cash fair value remeasurements related to the refinancing transactions that were completed in the second quarter of 2024.

Net Loss: Karyopharm reported a net loss of $33.1 million, or $3.82 net loss per basic and diluted share, for the third quarter of 2025, compared to a net loss of $32.1 million, or $3.85 net loss per basic and diluted share, for the third quarter of 2024. Net loss included non-cash stock-based compensation expense of $2.8 million and $4.2 million for the third quarters of 2025 and 2024, respectively.

Cash position: Prior to the receipt of approximately $32 million of net proceeds from the financing transactions announced by the Company on October 8, 2025, cash, cash equivalents, restricted cash and investments as of September 30, 2025 totaled $46.2 million, compared to $109.1 million as of December 31, 2024. On a proforma basis, cash, cash equivalents, restricted cash and investments would have been approximately $78 million. The Company’s cash balance as of September 30, 2025 reflects the benefit of $7.4 million of interest that was paid-in-kind and royalties that were deferred in connection with the Company’s financing transactions announced on October 8, 2025.

Conference Call Information

Karyopharm will host a conference call today, November 3, 2025, at 8:00 a.m. Eastern Time, to discuss the third quarter 2025 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 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.11

1.

American Cancer Society. Cancer Facts & Figures 2025. View Source Accessed October 15, 2025

2.

IARC GLOBOCAN 2022, Global Estimates

3.

Lu KH, et al. N Engl J Med. 2020;383:2053-2064

4.

NCI. Cancer stat facts: uterine cancer. View Source Accessed October 7, 2025

5.

American Cancer Society, Endometrial Cancer Risk Factors, 2025

6.

Leslie KK, et al. Gynecol Oncol. 2021;161(1):113-121.

7.

Vergote I, et al. J Clin Oncol. 2023;41(35):5400-5410.

8.

Mirza MR, et al. Presentation at: ESMO (Free ESMO Whitepaper) Congress; October 20-24, 2023

9.

Mirza MR, et al. N Engl J Med. 2023; 388:2145-2158.

10.

Eskander RN, et al. N Eng J Med. 2023;388:2159-2170.

11.

Makker V, et al. Gynecol Oncol. 2024 Jun:185: 202-211

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.

(Press release, Karyopharm, NOV 3, 2025, View Source [SID1234659263])

On November 3, 2025 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, reported that data from the ongoing Phase 1b study of R2891, a potent and selective inhibitor of dual interleukin receptor-associated kinases 1 and 4 (IRAK1/4), in patients with lower-risk myelodysplastic syndrome (MDS) who are relapsed or refractory (R/R) to prior therapies will be presented in an oral session at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Sunday, December 7, 2025. In addition, the ASH (Free ASH Whitepaper) Annual Meeting will feature four poster presentations with data for REZLIDHIA (olutasidenib) for the treatment of R/R mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML). The ASH (Free ASH Whitepaper) Annual Meeting is being held December 6-9, 2025, in Orlando, Florida and virtually.

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"We are very pleased to have the opportunity to highlight our hematology and oncology portfolio at ASH (Free ASH Whitepaper) this year," said Lisa Rojkjaer, M.D, Rigel’s chief medical officer. "In particular, we are delighted that updated results from our Phase 1b study in patients with relapsed or refractory lower-risk MDS have been accepted for oral presentation. Despite the availability of approved agents, there remains an unmet need for additional therapies to treat patients with transfusion dependent lower-risk MDS, and we look forward to advancing the dose expansion phase of the study to completion."

ASH Annual Meeting abstracts may be accessed online at www.hematology.org. Details of the oral and poster presentations, which will be available in the poster hall and via the virtual event platform, are as follows:

Oral Presentation

Sunday, December 7, 2025, 9:45am to 10:00am ET
Publication #: 489
Session Name: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Moving the Needle Through Novel Approaches in MDS and CMML
Presentation Title: An Update of Safety and Efficacy Results from a Phase 1b Study of R289, a Dual IRAK 1/4 Inhibitor, in Patients with Relapsed/Refractory (R/R) Lower Risk Myelodysplastic Syndrome (LR-MDS)
Presenter: Guillermo Garcia-Manero, M.D.

As of the data cutoff date (July 15, 2025), 33 patients were enrolled in the dose escalation part of the study. Patients had a median age of 75 with a median of 3 prior therapies and 61% were high transfusion burden at baseline.
Patients received R289 at doses ranging from 250 mg QD (once daily) to 500 mg BID (twice daily). For the 500 mg BID dose group, five patients were not yet evaluable (<16 weeks follow up) for determination of hematologic responses and one patient withdrew consent.
R289 was generally well tolerated across all dose groups, with the most frequent treatment emergent adverse events (≥20%) being diarrhea (28.1%), constipation/fatigue (25% each), and creatinine/alanine aminotransferase (ALT) increased (21.9% each), the majority being Grade 1/2. One (1) dose limiting toxicity (DLT) (Grade 4 aspartate aminotransferase (AST) increase/Grade 3 ALT increase) was reported in the 750 mg dose group.
For evaluable transfusion dependent patients (≥16 weeks follow up) at dose levels of at least 500 mg QD and higher, 4/13 patients (31%) achieved durable red blood cell transfusion independence (RBC-TI) for >8 weeks (500 mg QD [1/3], 750 mg QD [2/5], 500/250 mg QD [1/5]). Duration of RBC-TI was >16 weeks in 3 patients, >24 weeks in 2 patients, and >12 months in 1 patient. The median time to onset of RBC-TI was 2.2 months and the median duration of RBC-TI was 24.3 weeks.
All responding patients had R835 plasma concentrations similar to those at which ≥50% LPS-induced inhibition of cytokine release was observed in healthy volunteers, indicating a potential threshold for dose response (≥500 mg QD).
Updated data as of an October 28, 2025, data cutoff will be presented during the oral presentation.
Poster Presentations

Saturday, December 6, 2025, 5:30pm to 7:30pm ET
Publication #: 1659
Title: Clinical Characteristics and Response in Olutasidenib-Treated Relapsed/Refractory mIDH1 Acute Myeloid Leukemia (AML) Patients With Stable Disease Following Two Treatment Cycles
Presenter: Justin M. Watts, M.D.

In the pivotal cohort of the Phase 2 registrational study, of 147 patients with R/R mIDH1 AML who received olutasidenib, 36 (24%) patients maintained stable disease (SD) after 2 cycles of treatment. Treatment duration ranged from 2.6 to 51.1 months. In these 36 patients, the subsequent response rate was 33% (n=12), including 6 (17%) complete remission (CR), 2 (6%) CR with partial hematologic recovery (CRh), 1 (3%) CR with incomplete recovery, 1 (3%) morphologic leukemia-free state, and 2 (6%) partial remission.
Median time to best response from the start of treatment was 3.7 months (range: 2.8-5.7). 8 patients (22%) remained in SD and 16 (44%) had subsequent disease progression on study.
In the 12 late responders, median duration of response (DOR), duration of CR/CRh, and duration of CR were 9.9 months, 17.3 months, and not reached, respectively. Additionally, of the late responders who were transfusion dependent for platelets (n=6) or red blood cells (n=9) at baseline, 5 (83%) and 8 (89%), respectively, became transfusion independent.
Patients who achieved any late response had a longer median treatment duration (10.1 months) than non-responders. Median overall survival (OS) for late responders was 23.9 months and 32.7 months for those with CR/CRh.
Patients with SD after 2 cycles of olutasidenib may experience meaningful clinical benefit with continued treatment, as one-third of these patients subsequently achieved a late response, resulting in a lower risk of death compared to patients with no later response. These findings suggest that early SD may not predict treatment failure and support continuing olutasidenib for at least 6 cycles or until disease progression.
Sunday, December 7, 2025, 6:00pm to 8:00pm ET
Publication #: 4616
Title: Assessment of Real-World Treatment Patterns and Outcomes of Olutasidenib in Patients with Mutated Isocitrate Dehydrogenase 1 Acute Myeloid Leukemia Previously Treated with Venetoclax Using Electronic Health Record Data
Presenter: Catherine Lai, M.D., MPH

This retrospective cohort study analyzed data from Loopback Analytics’ electronic health records data in the U.S. until September 2024, incorporating structured clinical data and abstracted data from physician notes. Fourteen olutasidenib-treated patients in the Loopback database met inclusion criteria for the study.
The overall response rate (ORR) was 50% (7/14) and the composite complete remission (CRc) rate was 36% (5/14). Among patients who achieved any response, 86% (6/7) received venetoclax immediately prior to olutasidenib.
Median OS from olutasidenib initiation in the full cohort was 12.2 months, with the proportion of patients surviving 6, 9, and 12 months estimated to be 88%, 70%, and 53%, respectively.
In this real-world cohort, despite the small sample size, 50% of patients responded to post-venetoclax olutasidenib, consistent with the clinical efficacy observed in the pivotal Phase 2 trial. These findings support the use of olutasidenib as a viable therapeutic option in post-venetoclax treatment settings.
Publication #: 3439
Title: Analysis of Hematologic Improvement (HI) by Time to Response in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients Treated with Olutasidenib
Presenter: Shira N. Dinner, M.D

In the pivotal cohort of the Phase 2 registrational study (n=147), increases in hemoglobin were seen early in the course of treatment and levels continued to increase over 12 cycles. Similarly, platelet counts increased and blast percentages decreased over the course of treatment.
A total of 71 patients (48%) achieved an overall response; 47 patients (32%) achieved CR and 51 (35%) achieved CR/CRh. Among CR/CRh responders, 28 (55%) achieved a response in <2 months, 17 (33%) from 2 to 4 months, and 6 (12%) at >4 months.
Patients with a longer time to response tended to have lower baseline platelet counts and higher bone marrow blast percentages compared with earlier responders, suggesting lower hematopoietic reserve and greater disease burden.
In 37 patients (25%) who had a best response of SD, several showed improvement in platelets and hemoglobin levels by end of treatment. 7 of 21 (33%) patients with prior platelet transfusion dependence became independent and 7 of 23 (30%) with prior red blood cell transfusion dependence became independent.
This report highlights the hematological responses to olutasidenib in these patients with R/R mIDH1 AML and suggests that continuing olutasidenib treatment beyond 2 cycles may offer hematologic benefits, even in the absence of an early clinical response.
Monday, December 8, 2025, 6:00pm ET to 8:00pm ET
Publication #: 5213
Title: Olutasidenib Monotherapy in Patients With mIDH1 Acute Myeloid Leukemia Who Received Prior Intensive Chemotherapy
Presenter: Jay Yang, M.D.

In the pivotal cohort of the Phase 2 registrational study (n=147), in patients with prior intensive chemotherapy (IC), the ORR was 50% with 35/105 (33%) achieving CR and 38/105 (36%) achieving CR/CRh. Median DOR was 15.5 months, with median duration of CR not reached and CR/CRh of 17.6 months.
After a median follow up of 37.3 months, the median OS was 12.5 months. In comparison, in the 38 patients who received prior non-intensive therapy the ORR was 42%; 9/38 achieved CR and 10/38 achieved CR/CRh. The median DOR in this group was 16.2 months, with a median duration of CR and CR/CRh of 28.1 months and 29.0 months, respectively.
Among this cohort of patients with R/R mIDH1 AML who had received prior IC, treatment with olutasidenib monotherapy produced clinically meaningful response rates that closely align with those observed in the overall population, with durable responses and acceptable tolerability.
About R289
R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.2

About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 22,010 new cases in the United States, most in adults, in 2025.3

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.4,5 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.6 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

About REZLIDHIA

INDICATION
REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome
REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence.

Hepatotoxicity
REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.

DRUG INTERACTIONS

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.
Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
LACTATION
Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

GERIATRIC USE
No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

HEPATIC IMPAIRMENT
In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

Click here for Important Safety Information and Full Prescribing Information, including Boxed WARNING.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc.

(Press release, Rigel, NOV 3, 2025, View Source [SID1234659279])

On November 3, 2025 Pierre Fabre Pharmaceuticals Inc. (PFP) reported the transfer of the Biologics License Application (BLA) for tabelecleucel from Atara Biotherapeutics Inc. (Nasdaq: ATRA) with PFP now accountable for all aspects of the submission. Atara will continue to observe the regulatory process and provide support to PFP as needed. The tabelecleucel BLA has an FDA PDUFA target action date of January 10, 2026. If approved, the tabelecleucel will be indicated as monotherapy for treatment of adult and pediatric patients two years of age and older with EBV+ PTLD who have received at least one prior therapy.

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Atara resubmitted the tabelecleucel BLA on July 11, 2025 of this year, in collaboration with PFP, and the FDA accepted the tabelecleucel BLA with Priority Review on July 23. With completion of the transfer of the BLA, Pierre Fabre Laboratories and its subsidiaries are now responsible for all clinical development regulatory, commercial and manufacturing activities for tabelecleucel worldwide. The innovative cell therapy is manufactured by PFP in the US for global clinical development and commercial access.

"Transfer of the BLA represents another critical milestone in our efforts to bring this innovative cell therapy to EBV+ PTLD patients in the US who have limited treatment options and lifespan measured in only a few weeks to months following failure of initial treatment," said Adriana Herrera, chief executive officer of PFP, the Pierre Fabre Laboratories Pharmaceutical subsidiary in the U.S. "We look forward to our continued engagement with the FDA in completing the review of tabelecleucel BLA as we seek to transform outcomes for this ultra-rare, acute, and potentially deadly blood malignancy that occurs after transplantation."

Tabelecleucel is an investigational, allogeneic, off the shelf, EBV-specific T-cell immunotherapy which targets and eliminates EBV-infected cells. The BLA includes data covering more than 430 patients treated with tabelecleucel including the ongoing pivotal ALLELE study investigating the therapy in adults and children two years of age and older with relapsed or refractory EBV+ PTLD following SOT or HCT.

About EBV+PTLD
EBV+ PTLD is an ultra-rare, acute, and potentially deadly hematologic malignancy that occurs after transplantation when patient T-cell immune responses are compromised by immunosuppression. It can impact patients who have undergone solid organ transplant (SOT) or allogeneic HCT. Poor median survival of 3 weeks and 4.1 months for HCT and SOT, respectively, is reported in EBV+ PTLD patients for whom standard of care failed, underscoring the significant need for new therapeutic options.

About Tabelecleucel
Tabelecleucel is an allogeneic, off-the-shelf, EBV-specific T-cell immunotherapy designed to selectively target and eliminate EBV-infected cells. Unlike autologous CAR-T therapies, allogeneic T-cells are derived from third-party donors and are not genetically modified. Immune cells are collected from the blood of healthy donors and exposed to Epstein-Barr virus antigens to enrich for T cells that recognize EBV. These EBV T cells are expanded, characterized, kept alive, and stored for future use in treating patients.

(Press release, Pierre Fabre, NOV 3, 2025, View Source;302601901.html [SID1234659297])