On December 7, 2025 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on developing innovative CAR T-cell therapies, reported that clinical data from its allogeneic BCMA-targeted CAR T-cell product candidate, CT0596, for the treatment of relapsed/refractory multiple myeloma (R/R MM) was presented in a poster at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The poster was titled "A First-in-Human Study of CT0596, an Allogeneic CAR T-Cell Therapy Targeting BCMA, in Patients with Relapsed/Refractory Multiple Myeloma." The publication number was 2296.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This clinical trial (NCT06718270) enrolled 8 patients with R/R MM in the dose-escalation phase who received CT0596 infusion. The median number of prior lines of therapy was 4.5 (range: 3-9). Enrollment was not restricted by NKG2A expression levels. Regarding lymphodepletion, 6 patients received full-dose lymphodepletion with fludarabine (30 mg/m²/day) and cyclophosphamide (500 mg/m²/day) for 3 consecutive days, while 2 patients received reduced-dose lymphodepletion. CT0596 was administered at dose levels of 1.5×10⁸ (n=1), 3×10⁸ (n=5), and 4.5×10⁸ CAR-T cells (n=2), with one patient receiving two infusions.

As of August 31, 2025, all 8 infused patients were evaluable for efficacy, with a median follow-up of 4.14 months (range: 0.9-7.9 months). Six patients achieved a partial response (PR) or better: 3 achieved complete response/stringent complete response (CR/sCR) (all in the full-dose lymphodepletion group), 1 achieved very good partial response (VGPR), and 2 achieved PR. Among the 6 patients who received full-dose lymphodepletion, 5 achieved PR or better. Six patients in the full-dose lymphodepletion group achieved minimal residual disease (MRD)-negativity at Week 4. Patient 01 maintained ongoing sCR and MRD-negativity as of Month 8. Patient 04 achieved PR with resolution of extramedullary disease following the second infusion. CAR-T cell expansion was observed in all 8 patients. Among the two patients who received the 4.5×10⁸ dose, one achieved sCR, and the other exhibited deepening response to VGPR.

CT0596 demonstrated a manageable safety profile. Four patients experienced Grade 1 cytokine release syndrome (CRS); no Grade 2 or higher CRS was observed. No immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD) was reported. No dose-limiting toxicities, treatment discontinuations, or deaths were observed.

The study is still in the dose-exploration phase. The lymphodepletion regimen has been determined, and higher cell doses are being explored to further define the recommended dose (RD). The company plans to initiate a Phase 1b registrational study for CT0596 in 2026.

About CT0596

CT0596 is an allogeneic BCMA-targeted CAR-T therapy developed using CARsgen’s proprietary THANK-u Plus platform. It is currently being evaluated in investigator-initiated trials for relapsed/refractory multiple myeloma (R/R MM) or plasma cell leukemia (PCL). CT0596 demonstrated preliminary favorable tolerability and encouraging efficacy signals. Further investigation is planned in additional plasma cell malignancies and autoimmune diseases mediated by autoreactive plasma cells. The company anticipates submitting an Investigational New Drug (IND) application in the second half of 2025.

(Press release, Carsgen Therapeutics, DEC 7, 2025, View Source [SID1234661222])

On December 7, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported encouraging data from the Phase 1/2 LINKER-MM4 trial evaluating Lynozyfic (linvoseltamab) in adults with newly diagnosed multiple myeloma (NDMM) who were transplant eligible or ineligible were shared in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. These data build on results from a broad clinical development program evaluating Lynozyfic in early lines of treatment, including precursor conditions, as monotherapy and in combination with standard-of-care or novel agents.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The treatment of newly diagnosed multiple myeloma often relies on complicated combinations of quadruplet or triplet regimens, each with its own toxicities, in order to achieve rapid and durable responses, which can be incredibly burdensome for these patients," said Robert Orlowski, M.D., Ph.D., Deputy Chair, Professor of Medicine, and Director of Translational Myeloma Research in the Departments of Lymphoma/Myeloma and Experimental Therapeutics at The University of Texas MD Anderson Cancer Center and the lead investigator for the LINKER-MM4 trial. "As the first to evaluate a BCMAxCD3 bispecific monotherapy in this setting, LINKER-MM4 seeks to understand whether frontline intervention with a single agent can deliver strong efficacy, enabling the simplification and potentially greater tolerability of these regimens. Lynozyfic monotherapy is already achieving MRD negativity rates comparable to quadruplet regimens but earlier in the treatment course, and these compelling results are expected to deepen with longer follow up. These results underscore Lynozyfic’s potential as a foundational component of frontline treatment regimens for multiple myeloma – or even a monotherapy regimen – for both transplant-eligible and transplant-ineligible patients."

LINKER-MM4 is an ongoing, open-label Phase 1/2 trial investigating Lynozyfic in adults with NDMM. During a Phase 1A (dose escalation) cohort, patients were treated with a step-up dosing regimen followed by 50 mg, 100 mg or 200 mg doses of Lynozyfic. The lowest (50 mg) and highest (200 mg) tolerated doses were selected for further evaluation in the Phase 1B (dose-expansion) cohort. Among the 45 treated patients in both Phase 1A and 1B, 28 were transplant eligible, and 17 were transplant ineligible.

Across all dose levels (n=45), there was a 1.2 months median time to onset of response (range: 1-4.5 months). All three dose groups (50 mg, 100 mg and 200 mg) showed impressive efficacy, with a VGPR+ (very good partial response or better) of ≥70% with limited follow-up. Evidence shows that these responses are expected to deepen over time. Across all dose groups, 95% (19 of 20 patients) of all minimum residual disease (MRD) evaluable VGPR+ patients achieved MRD negative status at 10-5 sensitivity.

Across all dose levels, the most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS; all Grade 1: 44%) and neutropenia (any Grade: 38%; Grade 3/4: 33%). Among other adverse events of special interest, one patient in the 50 mg cohort experienced Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). Infections occurred in 84% of patients (Grade 1/2: 51%; Grade 3: 33%) with the majority occurring within the first three months of treatment and the rate of infections decreased over time. There were no ≥Grade 4 infections, Grade 5 TEAEs or dose-limiting toxicities. Ten patients elected to undergo an autologous stem cell transplant, all of whom had an acceptable CD34+ stem cell yield post-induction (range: 2.5-11.5 x 106/kg).

A broad clinical development program investigating Lynozyfic in early stages of the disease is underway. This includes the Phase 2 portion of the LINKER-MM4 trial evaluating Lynozyfic at the recommended 200 mg dose, as well as LINKER-MM6 (EMN39), a trial evaluating a combination of daratumumab, lenalidomide and dexamethasone (DRd) followed by Lynozyfic monotherapy compared with continued DRd in transplant-ineligible NDMM.

The use of Lynozyfic described above is investigational, and its safety and efficacy has not been evaluated by any regulatory authority for this indication.

About the ‘Regeneron Roundtable’ Investor Event
Regeneron will host a virtual investor event to discuss its multiple myeloma program on Wednesday, December 10 at 8:30 a.m. ET. This is the next webcast in a new investor event series called the ‘Regeneron Roundtable,’ intended to highlight programs from the company’s innovative investigational pipeline.
 
Links to the webcast and to register via telephone may be accessed from the ‘Investors and Media’ page of Regeneron’s website at View Source Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.

About Multiple Myeloma
As the second most common blood cancer, there are over 187,000 new cases of MM diagnosed globally every year, with more than 36,000 diagnosed and 12,000 deaths anticipated in the U.S. in 2025. The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable, and while current treatments are able to slow progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.

About Lynozyfic
Lynozyfic was invented using Regeneron’s VelocImmune technology and is a fully human BCMAxCD3 bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing. Lynozyfic is approved to treat certain adults with R/R MM: in the U.S. after four lines of therapy and in the European Union after at least three prior therapies.

In the U.S., the generic name for Lynozyfic in its approved indications is linvoseltamab-gcpt, with gcpt as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA. Outside of the U.S., the generic name of Lynozyfic in its approved indications is linvoseltamab.

Lynozyfic is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens across different lines of therapy in MM, including earlier lines of treatment, as well as plasma cell precursor disorders. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority. 

In addition to LINKER-MM4, ongoing trials include:

LINKER-MM1: Phase 1/2 dose-escalation and dose-expansion trial evaluating the safety, tolerability, dose-limiting toxicities and anti-tumor activity of Lynozyfic monotherapy in R/R MM
LINKER-MM2: Phase 1b, open-label trial evaluating Lynozyfic in combination with other cancer treatments in patients with R/R MM
LINKER-MM3: Phase 3 confirmatory trial evaluating Lynozyfic monotherapy compared to the combination of elotuzumab, pomalidomide and dexamethasone in R/R MM
LINKER-MM5: Phase 3 trial evaluating Lynozyfic monotherapy or in combination with carfilzomib compared to standard of care combination regimens in patients with R/R MM
LINKER-MM6 (EMN39): Phase 3 trial, in collaboration with the European Myeloma Network, evaluating daratumumab, lenalidomide and dexamethasone induction followed by Lynozyfic monotherapy compared to continued daratumumab, lenalidomide, and dexamethasone in NDMM who are transplant-ineligible
Phase 1 trial evaluating Lynozyfic in combination with a Regeneron CD38xCD28 costimulatory bispecific in R/R MM
LINKER-SMM1: Phase 2 trial evaluating Lynozyfic monotherapy in high-risk smoldering MM
LINKER-MGUS1: Phase 2 dose-ranging trial evaluating Lynozyfic monotherapy in high-risk monoclonal gammopathy of unknown significance and non-high-risk SMM
LINKER-AL2: Phase 1/2 trial evaluating Lynozyfic monotherapy in R/R systemic light chain amyloidosis
For more information on Regeneron’s clinical trials in blood cancer, visit the clinical trials website, or contact via [email protected] or 844-734-6643.

IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS

What is the most important information I should know about LYNOZYFIC?
LYNOZYFIC may cause serious or life-threatening side effects, including Cytokine Release Syndrome (CRS) and infusion-related reactions (IRR), or neurologic problems.

Cytokine Release Syndrome (CRS) and infusion related reactions (IRR). CRS is common during treatment with LYNOZYFIC and can also be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS or IRR, including:

fever of 100.4ºF (38ºC) or higher
fast heartbeat
chills or shaking
dizziness or light-headedness
trouble breathing

Neurologic problems. LYNOZYFIC can cause neurologic problems that can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of neurologic problems, including:

headache
agitation, trouble staying awake, confusion or disorientation, seeing or hearing things that are not real (hallucinations)
trouble speaking, writing, thinking, remembering things, paying attention, or understanding things
problems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms
numbness and tingling (feeling like "pins and needles")
burning, throbbing, or stabbing pain
changes in your handwriting
seizures
Due to the risk of CRS and neurologic problems, you will receive LYNOZYFIC on a "step-up dosing schedule" and should be hospitalized for 24 hours after the first and second "step-up" doses.

During the "step-up dosing schedule":
For your first dose, you will receive a smaller "step-up" dose of LYNOZYFIC on Day 1 of your treatment.
For your second dose, you will receive a larger "step-up" dose of LYNOZYFIC, which is usually given on Day 8 of your treatment.
For your third dose, you will receive the first treatment dose of LYNOZYFIC, which is usually given on Day 15 of your treatment.
Your healthcare provider may repeat one or both of the "step-up" doses depending on side effects or if your treatment is delayed.
Before the "step-up" doses and the first two treatment doses of LYNOZYFIC, you will receive medicines to help reduce your risk of CRS and IRR. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of side effects with future doses.
LYNOZYFIC is available only through the LYNOZYFIC Risk Evaluation and Mitigation Strategy (REMS) due to the risk of side effects of CRS and neurologic problems. You will receive a Patient Wallet Card from your healthcare provider. Carry the LYNOZYFIC Patient Wallet Card with you at all times and show it to all of your healthcare providers. The LYNOZYFIC Patient Wallet Card lists signs and symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the signs and symptoms listed on the LYNOZYFIC Patient Wallet Card. You may need to be treated in a hospital.

Your healthcare provider will monitor you for signs and symptoms of CRS and neurologic problems during treatment with LYNOZYFIC, as well as other side effects, and may treat you in a hospital if needed. Your healthcare provider may temporarily stop or completely stop your treatment with LYNOZYFIC if you develop CRS, neurologic problems, or any other severe side effects.

If you have any questions about LYNOZYFIC, ask your healthcare provider.

Before receiving LYNOZYFIC, tell your healthcare provider about all of your medical conditions, including if you:

have an infection.
are pregnant or plan to become pregnant. LYNOZYFIC may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with LYNOZYFIC.
Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with LYNOZYFIC.
You should use an effective form of birth control (contraception) during treatment with LYNOZYFIC and for 3 months after your last dose of LYNOZYFIC.
are breastfeeding or plan to breastfeed. It is not known whether LYNOZYFIC passes into your breast milk. Do not breastfeed during treatment with LYNOZYFIC and for 3 months after your last dose of LYNOZYFIC.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive LYNOZYFIC?

LYNOZYFIC will be given to you by your healthcare provider by infusion through a needle placed in a vein (intravenous infusion).
After the "step-up dosing schedule", the treatment dose of LYNOZYFIC is usually given 1 time each week for 11 doses, and then 1 time every other week for 5 doses. After these doses and based on how your disease responds, your healthcare provider will decide if you are able to receive LYNOZYFIC less often (every 4 weeks) or will continue to have every other week treatment.
Your healthcare provider will decide how long you will receive treatment with LYNOZYFIC.
If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. It is important for you to be monitored closely for side effects during treatment with LYNOZYFIC.
What should I avoid while receiving LYNOZYFIC?
Do not drive, or operate heavy or potentially dangerous machinery, or do other dangerous activities for 48 hours after completing each of your "step-up" doses or at any time during treatment with LYNOZYFIC if you develop new neurologic symptoms, until the symptoms go away.

What are the possible side effects of LYNOZYFIC?
LYNOZYFIC may cause serious side effects, including:

Infections. LYNOZYFIC can cause bacterial, viral, or fungal infections that are serious, life-threatening, or that may lead to death. Upper respiratory tract infections and pneumonia are common during treatment with LYNOZYFIC.
Your healthcare provider will monitor you for signs and symptoms of infection before and during treatment with LYNOZYFIC.
Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with LYNOZYFIC.
Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with LYNOZYFIC, including:
fever of 100.4 °F (38 °C) or higher
chills
cough
shortness of breath
chest pain
sore throat
pain during urination
feeling weak or generally unwell
Decreased white blood cell counts. Decreased white blood cell counts are common during treatment with LYNOZYFIC and can also be severe. Fever can happen with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will check your blood cell counts before you start treatment and during treatment with LYNOZYFIC, and will treat you as needed.
Liver problems. LYNOZYFIC can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Your healthcare provider will do blood tests to check your liver before starting and during treatment with LYNOZYFIC. Tell your healthcare provider if you develop any of the following signs or symptoms of liver problems:
tiredness
loss of appetite
pain in your right upper stomach-area (abdomen)
dark urine yellowing of your skin or the white part of your eyes
The most common side effects of LYNOZYFIC include:

muscle and bone pain
nausea
cough
headache
diarrhea
tiredness or weakness
shortness of breath
The most common severe abnormal blood test results with LYNOZYFIC include: low white blood cell counts and low red blood cell counts.

These are not all of the possible side effects of LYNOZYFIC.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see full Prescribing Information, including Boxed WARNING, and Medication Guide for LYNOZYFIC.

What is LYNOZYFIC?
LYNOZYFIC is a prescription medicine used to treat adults with multiple myeloma who:

have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody to treat their multiple myeloma, and
their cancer has come back or did not respond to prior treatment.
It is not known if LYNOZYFIC is safe and effective in children.

About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.

Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in various combinations and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.

Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA-approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.

(Press release, Regeneron, DEC 7, 2025, View Source [SID1234661207])

On December 7, 2025 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, reported updated data from its ongoing Phase 1b study evaluating R2891, an oral prodrug of R835, a potent and selective dual inhibitor of interleukin receptor-associated kinases 1 and 4 (IRAK1/4), in patients with relapsed or refractory (R/R) lower-risk myelodysplastic syndrome (MDS). The data are being presented today in an oral session by Dr. Guillermo Garcia-Manero at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 6-9, in Orlando, Florida and virtually.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"New therapies are needed for patients with transfusion dependent lower-risk MDS. We’re pleased to share these updated study results, which underscore the potential of R289 to become a treatment option for these patients," said Lisa Rojkjaer, M.D., Rigel’s chief medical officer. "We look forward to concluding the dose expansion phase of the study and anticipate selection of the recommended Phase 2 dose for future clinical studies in the second half of 2026."

Rigel’s open-label Phase 1b study of R289 is evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy in patients with R/R lower-risk MDS (NCT05308264). Enrollment in the dose escalation phase of the study was completed in July 2025. In October 2025, the first patient was dosed in the dose expansion phase where up to 40 patients will be randomized to either 500 mg once or twice daily to determine the recommended Phase 2 dose for future clinical trials.

Key highlights from the updated data as of October 28, 2025, include:

33 patients were enrolled, representing a difficult-to-treat population. The median age was 75. The median number of prior therapies was 3 (range: 1-8); 76% (25) of patients had received luspatercept, 73% (24) had received an erythropoiesis stimulating agent (ESA), 67% (22) had received an hypomethylating agent (HMA) and 6% (2) had received imetelstat. 61% (20) of patients were high transfusion burden (HTB) at baseline. 67% (22) of patients were ring sideroblast (RS) negative.
Median duration of treatment was 5.5 months (range: 0.9 – 27.7 months). R289 was generally well tolerated across all dose groups in this heavily pre-treated lower-risk MDS patient population, the majority of whom were HTB at baseline. The most common Grade 1/2 treatment-emergent adverse events (TEAEs) (in ≥18% of patients) were diarrhea (n=10, 30%), constipation and fatigue (each n=9, 27%), and creatinine increased and cough (each n=7, 21%). The most frequent Grade 3/4 TEAEs were anemia (n=6, 18%), neutrophil count decreased and pneumonia (each n=5, 15%), and alanine aminotransferase (ALT) increased and aspartate aminotransferase (AST) increased (each n=3, 9%). One (1) dose limiting toxicity (DLT) (Grade 4 AST increased/Grade 3 ALT increased) was reported in the 750 mg dose group.
For evaluable transfusion dependent (TD) patients (≥16 weeks follow up) at dose levels of at least 500 mg QD and higher, 6/18 (33%) patients achieved durable red blood cell transfusion independence (RBC-TI) of >8 weeks [500 mg QD (1/3), 750 mg QD (2/5), 500/250 mg QD (1/5), 500 mg BID (2/5)]. Duration of RBC-TI was >16 weeks in 4 patients and >24 weeks in 3 patients. The median time to onset of RBC-TI was 1.9 months and the median duration of RBC-TI was 22.9 weeks. Peak hemoglobin increases of 2.9 to 6.1 g/dL compared to baseline occurred in patients achieving RBC-TI.
Of the 6 patients achieving RBC-TI, 5 had received an HMA.
At doses ≥500 mg QD, steady state R835 plasma concentrations reached or exceeded those associated with 50-90% inhibition of lipopolysaccharide (LPS)-induced cytokine release previously observed in healthy volunteers.
Oral presentation details are as follows:

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.

R289 was previously granted Orphan Drug designation for the treatment of myelodysplastic syndromes and granted Fast Track designation for the treatment of previously-treated transfusion dependent lower-risk MDS by the FDA.

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.

(Press release, Rigel, DEC 7, 2025, View Source [SID1234661208])

On December 7, 2025 Incyte (Nasdaq:INCY) reported new clinical data from two Phase 1 studies evaluating the safety, tolerability and efficacy of INCA033989, a first-in-class mutant calreticulin (mutCALR)-targeted monoclonal antibody, for patients with mutCALR-expressing myeloproliferative neoplasms (MPNs). These preliminary results are from the dose escalation portion of the studies evaluating INCA033989 as a monotherapy in patients with myelofibrosis (MF) harboring a CALR mutation who are resistant, intolerant to or ineligible for JAK inhibitor treatment, and INCA033989 in combination with ruxolitinib (Jakafi) in patients who experienced a suboptimal response to ruxolitinib monotherapy. These data are being featured in oral presentations (Session 634, Publication #484; Session 631, Publication #71) at the 2025 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These positive study results reinforce our confidence in INCA033989’s transformative potential, both as a targeted monotherapy and combination therapy for MF, building on the positive results previously reported in essential thrombocythemia (ET)," said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. "Our goal is to bring new targeted treatment options to patients across the MPN disease spectrum. In line with this commitment, we plan to initiate a registrational program evaluating INCA033989 for the treatment of patients with MF in 2026."

The preliminary analysis (data cut off September 25, 2025) evaluated the safety and efficacy of INCA033989 in patients with MF as measured by spleen volume reduction ≥25% (SVR25) and ≥35% (SVR35), change in MPN-Symptom Assessment Form (SAF), total symptom score (TSS), anemia response and mutCALR variant allele frequency (VAF) reduction.

In the monotherapy arm of the trials, patients with MF treated with INCA033989 (dose range 24 to 2,500 mg) experienced rapid and robust spleen and anemia responses and symptom improvements. Specifically:

At Week 24, 41.7% (15/36) of all evaluable MF patients achieved SVR25, and 33.3% (12/36) achieved SVR35. Among MF patients not previously treated with a JAK inhibitor, 71.4% (5/7) achieved SVR25 and 57.1% (4/7) achieved SVR35. Among those resistant or intolerant to JAK inhibitor treatment, 34.5% (10/29) and 27.6% (8/29) achieved SVR25 and SVR35 at Week 24, respectively.
Anemia response occurred in more than half (56%; 14/25) of evaluable anemic MF patients, with 40% (10/25) of patients achieving a major response with INCA033989 treatment.
Nearly all MF patients treated with INCA033989 (93.3%; 42/45) experienced improved symptoms, with 60% (27/45) achieving a ≥50% reduction in TSS (TSS50) as best response. At Week 24, 39.4% (13/33) of patients achieved a TSS50.
Most patients (89.4%; 42/47) with ≥1 post-baseline VAF measurement experienced a reduction in mutCALR VAF, and 10.6% (5/47) achieved a ≥25% best reduction in VAF.
Most patients (76.5%; 39/51) in the studies had co-occurring mutations. Of those, 40.5% (15/37) of response eligible patients achieved SVR35 or an anemia response. Single-cell analyses in MF patients with high clonal complexity, including high-risk mutations, showed consistent reductions in all CALR-mutant clones, regardless of the presence of co-occurring variants.
Similarly, in the INCA033989 (dose range 70 to 2,500 mg) and ruxolitinib combination arm of the trials, most MF patients experienced spleen volume reductions and symptom improvements:

At Week 24, half (50%; 6/12) of all evaluable MF patients achieved SVR25 and 25% (3/12) achieved SVR35.
Among the 14 evaluable patients, 86% had stable anemia and one (1) patient with non-transfusion dependent anemia had a major anemia response.
The majority of MF patients (81.3%; 13/16) treated with INCA033989 in combination with ruxolitinib experienced symptom improvement, and 33.3% (3/9) achieved TSS50 at Week 24.
Additionally, exploratory analyses in a subset of MF patients from the studies showed that INCA033989 reduced circulating mutCALR-positive hematopoietic stem and progenitor cells (HSPC) and mutCALR-positive platelet producing cells called megakaryocytes (MK) in the bone marrow, and improved marrow architecture, as measured by increased wild type (mutCALR-negative) MK. Among evaluable anemic MF patients (n=12), erythroid progenitor cells (CD71+ by IHC) in the bone marrow increased, correlating with hemoglobin increase and clinical anemia response. Together, these findings demonstrate the disease-modifying activity of INCA033989 in patients with mutCALR-expressing MF.

INCA033989 was well-tolerated, both as a monotherapy and in combination with ruxolitinib, in patients with MF who were resistant or intolerant to prior JAK inhibitor therapy or ineligible for JAK inhibitor treatment, with no dose-limiting toxicities observed.

In the monotherapy arm (n=52), 86.5% (45) of patients were still receiving treatment and 13.5% (7) discontinued treatment. Only two (2) patients discontinued treatment due to treatment-emergent adverse events (TEAEs). Two (2) dose and three (3) infusion interruptions due to TEAEs were reported, and a maximum tolerated dose was not reached (dose range 24 to 2,500 mg). Fifty (50) patients across the monotherapy dose cohorts reported a TEAE, 30 of which were deemed treatment related.
The most common TEAEs (>20%) were anemia, fatigue, thrombocytopenia, arthralgia, AST elevations, cough, diarrhea, headache, leukopenia, nausea and pruiritis – nearly all were Grade 1. Sixteen (16) patients had Grade ≥3 TEAEs, with neutropenia being the most frequent (9.6%).
In the combination therapy arm (n=20), 85.0% (17) patients were still receiving treatment and 15.0% (3) discontinued treatment. Only two patients discontinued treatment due to TEAEs. One (1) dose and one (1) infusion interruption due to TEAEs were reported, and a maximum tolerated dose was not reached (dose range 70 to 2,500 mg). Twenty (20) patients across the combination therapy dose cohorts reported a TEAE, 13 of which were deemed treatment related.
The most common TEAEs (>20%) were anemia, thrombocytopenia, ALT increase, diarrhea and fatigue. Eleven (11) patients experienced Grade ≥3 TEAEs, with anemia (30%) being the most frequent.
"Widely regarded as the most aggressive type of MPN – a group of rare, chronic blood cancers – MF is characterized by bone marrow fibrosis, anemia and splenomegaly, which can lead to debilitating symptoms and increased mortality," said John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mt. Sinai and Director, Center of Excellence for Blood Cancers and Myeloid Disorders, The Tisch Cancer Institute. "The Phase 1 data evaluating INCA033989 alone and in combination with ruxolitinib offer compelling proof-of-concept for a differentiated, targeted treatment approach in MF. The early signals observed suggest the potential to meaningfully influence the MF disease course, and I look forward to seeing this therapy advance in future clinical studies."

More information regarding Incyte’s presentations at the 2025 ASH (Free ASH Whitepaper) Annual Meeting can be found on the ASH (Free ASH Whitepaper) website: View Source

In addition to MF, INCA033989 is also being evaluated in Phase 1 studies for the treatment of patients with essential thrombocythemia (ET). The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy designation to INCA033989 for the treatment of patients with ET harboring a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy. The company plans to initiate a registrational program evaluating INCA033989 for the treatment of patients with ET harboring a Type 1 or non-Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy in 2026.

Incyte Conference Call and Webcast
Incyte will host an investor event and webcast on Sunday, December 7, 2025, from 11:00 – 12:30 p.m. ET to discuss key mutCALR data presented at ASH (Free ASH Whitepaper).

The event will be webcasted and can be accessed via the Events and Presentations tab of the Investor section of Incyte.com and it will be available for replay for 30 days.

About Myeloproliferative Neoplasms (MPNs) and Mutations in Calreticulin (mutCALR)
Calreticulin (CALR) is a protein involved in the regulation of cellular calcium levels and normal protein folding. Somatic, or non-inherited, DNA mutations in the CALR gene (mutCALR) can result in abnormal protein function and lead to the development of myeloproliferative neoplasms (MPNs),1 a closely related group of clonal blood cancers in which the bone marrow functions abnormally, overproducing blood cells.2,3 Among two types of MPNs, essential thrombocythemia (ET) and myelofibrosis (MF), mutCALR drives 25-35% of all cases.1,2

Incyte is at the forefront of developing novel therapies for patients with mutCALR ET or MF that target only malignant cells, sparing normal cells, including INCA033989, a first-in-class, mutCALR-specific therapy.

About the INCA033989 Trial Program
The clinical trial program for INCA033989 includes two multicenter, open-label Phase 1 studies, INCA33989-101 (NCT05936359) and INCA33989-102 (NCT06034002). The studies are evaluating the safety, tolerability and efficacy of INCA033989 in ~455 adult (≥18 years old) patients with mutCALR-expressing myeloproliferative neoplasms (MPNs), including myelofibrosis (MF) and essential thrombocythemia (ET).

The primary endpoint of the studies is measured by the number of participants with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs) and the number of participants with TEAEs leading to dose modification or discontinuation. Secondary endpoints include response rates, mean change of ET total symptom score, percentage of MF patients achieving spleen volume reduction, MF patient anemia response, mean change in disease-related allele burden and various pharmacokinetics measures.

For more information on the studies, please visit: View Source and View Source

About Jakafi (ruxolitinib)
Jakafi (ruxolitinib) is a JAK1/JAK2 inhibitor approved by the U.S. FDA for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea; intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults; steroid-refractory acute GVHD in adult and pediatric patients 12 years and older; and chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Jakafi is a registered trademark of Incyte.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi (ruxolitinib) may cause low platelet, red blood cell, and white blood cell counts. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will do a blood test to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.

Cancer: Some people have had certain types of non-melanoma skin cancers during treatment with Jakafi. Your healthcare provider will regularly check your skin during your treatment with Jakafi. Tell your healthcare provider if you develop any new or changing skin lesions during treatment with Jakafi.

Increases in cholesterol: You may have changes in your blood cholesterol levels during treatment with Jakafi. Your healthcare provider will do blood tests to check your cholesterol levels about every 8 to 12 weeks after you start taking Jakafi, and as needed.

Increased risk of major cardiovascular events such as heart attack, stroke or death in people who have cardiovascular risk factors and who are current or past smokers while using another JAK inhibitor to treat rheumatoid arthritis: Get emergency help right away if you have any symptoms of a heart attack or stroke while taking Jakafi, including: discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back, severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw, pain or discomfort in your arms, back, neck, jaw, or stomach, shortness of breath with or without chest discomfort, breaking out in a cold sweat, nausea or vomiting, feeling lightheaded, weakness in one part or on one side of your body, slurred speech.

Increased risk of blood clots: Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) have happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening. Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with Jakafi, including: swelling, pain, or tenderness in one or both legs, sudden, unexplained chest or upper back pain, shortness of breath or difficulty breathing.

Possible increased risk of new (secondary) cancers: People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers. People who smoke or who smoked in the past have an added risk of new cancers.

The most common side effects of Jakafi include: for certain types of myelofibrosis (MF) and polycythemia vera (PV) – low platelet or red blood cell counts, bruising, dizziness, headache, and diarrhea; for acute GVHD – low platelet counts, low red or white blood cell counts, infections, and swelling; and for chronic GVHD – low red blood cell or platelet counts and infections including viral infections.

These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Call your doctor for medical advice about side effects.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had low white or red blood cell counts, have or had tuberculosis (TB) or have been in close contact with someone who has TB, had shingles (herpes zoster), have or had hepatitis B, have or had liver or kidney problems, are on dialysis, have high cholesterol or triglycerides, had cancer, are a current or past smoker, had a blood clot, heart attack, other heart problems or stroke, or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change your dose or stop taking Jakafi without first talking to your healthcare provider.

Women should not take Jakafi while pregnant or planning to become pregnant. Do not breastfeed during treatment with Jakafi and for 2 weeks after the final dose.

Please see the Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

You may also report side effects to Incyte Medical Information at 1-855-463-3463.

On December 7, 2025 Incyte (Nasdaq:INCY) reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to INCA033989, a first-in-class mutant calreticulin (mutCALR)-targeted monoclonal antibody, for the treatment of patients with essential thrombocythemia (ET) harboring a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ET is a chronic myeloproliferative neoplasm (MPN) characterized by persistently elevated platelet counts due to abnormal blood cell production in the bone marrow. CALR mutations are the second most common oncogenic driver mutation and are observed in 25% of patients with ET. A 52-bp deletion, also known as a Type 1 mutation, occurs in 55% of patients with a CALR mutation, and is associated with the highest risk of transformation to myelofibrosis (MF) among all ET patients.

"Incyte has long been committed to improving outcomes for patients with MPNs, and this Breakthrough Therapy designation underscores the potential of INCA033989 to be a novel therapy that could significantly transform the treatment of ET patients, who today have limited treatment options," said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. "The designation allows us to expedite the development pathway for INCA033989 in patients with Type 1 mutations. Looking ahead, we plan to initiate a Phase 3 program evaluating INCA033989 in ET patients with all types of CALR mutations in mid-2026, following alignment with regulators in the first half of next year."

The FDA Breakthrough Therapy Designation was supported by the early Phase 1 data evaluating INCA033989 in ET patients with a Type 1 CALR mutation available at the time of submission.

The preliminary Phase 1 data were presented earlier this year at the 2025 European Hematology Association (EHA) (Free EHA Whitepaper) Congress. In the study, INCA033989 was well-tolerated and demonstrated rapid and durable normalization of platelet counts across evaluated doses, with greater responses seen at higher doses across both mutation types. Updated results from the Phase 1 dose escalation and expansion trial are planned for presentation at the 2025 ASH (Free ASH Whitepaper) Annual Meeting in Orlando (Session 634; Publication #1024; December 8, 4:30-6:00 p.m. ET).

Incyte plans to develop INCA033989 for patients with Type 1 and non-Type 1 CALR mutations and, following discussions with regulatory agencies, plans to initiate a registrational program evaluating patients with ET with a Type 1 or non-Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy in the first half of next year.

About Essential Thrombocythemia
Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by persistently elevated platelet counts due to abnormal blood cell production in the bone marrow. People living with ET are at increased risk for blood clots and bleeding and a proportion of patients may progress over time to myelofibrosis or acute leukemia.

About Mutations in Calreticulin (mutCALR)
Calreticulin (CALR) is a protein involved in the regulation of cellular calcium levels and normal protein folding. Somatic, or non-inherited, DNA mutations in the CALR gene (mutCALR) can result in abnormal protein function and lead to the development of myeloproliferative neoplasms (MPNs),1 a closely related group of clonal blood cancers in which the bone marrow functions abnormally, overproducing blood cells.2,3 In Essential thrombocythemia (ET) and myelofibrosis (MF), CALR mutations occur in ~25-35% of patients.1,2

Incyte is at the forefront of developing novel therapies for patients with mutCALR ET or MF that target only malignant cells, sparing normal cells, including INCA033989, a first-in-class, mutCALR-specific therapy.

(Press release, Incyte, DEC 7, 2025, View Source [SID1234661225])