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Incyte’s First-in-Class mutCALR-Targeted Monoclonal Antibody, INCA033989, Granted Breakthrough Therapy Designation by U.S. FDA

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.

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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])

Incyte Announces New Positive Data for INCA033989, its First-In-Class mutCALR-Targeted Monoclonal Antibody, in Patients with Myelofibrosis Presented at ASH 2025

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.

"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

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.

CARsgen Announces Data of Allogeneic BCMA CAR-T Cell Therapy CT0596 for Relapsed/Refractory Multiple Myeloma at the 2025 ASH Annual Meeting

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.

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])

Innovent Biologics Announces Initial Results of the First-in-Human Phase 1 Study of Trispecific Antibody IBI3003 in Relapsed or Refractory Multiple Myeloma

On December 7, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures, and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major disease areas, reported the initial data of the first-in-human trial of IBI3003, a novel trispecific antibody targeting G protein-coupled receptor C5D (GPRC5D), B-cell maturation antigen (BCMA), and CD3 for the treatment of relapsed or refractory multiple myeloma (R/R MM), in an oral presentation at the 2025 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. IBI3003 demonstrated favorable tolerability and a manageable safety profile. Despite the relatively short follow-up duration, IBI3003 has shown encouraging efficacy signals, particularly in high-risk patients with extramedullary disease (EMD) or those who have previously received anti-BCMA and/or anti-GPRC5D targeted therapies.

IBI3003 is a novel trispecific antibody targeting GPRC5D, BCMA and CD3 simultaneously. Its dual-targeting design against BCMA and GPRC5 aims to overcome single antigen escape in multiple myeloma (MM). In preclinical studies, IBI3003 exhibited superior in vivo anti-tumor activity over marketed benchmark bispecific antibodies in mouse models, with particularly prominent tumor-killing efficacy in in vitro cell models with low expression of BCMA and GPRC5D. Currently, Innovent is conducting a Phase 1/2 clinical trial (NCT06083207) of IBI3003 in China and Australia to evaluate its safety, tolerability, and efficacy in patients with R/R MM.

The first phase of the study enrolled eligible R/R MM patients who had failed ≥2 lines of previous anti-myeloma therapies that included at least a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 mAb; and must be relapsed or refractory to their last anti-myeloma regimen. Prior BCMA- or GPRC5D-targeting therapy was allowed.

IBI3003 was administered subcutaneously once weekly (QW). For patients who have received continuous treatment for ≥6 months and achieved partial response (PR) or better for ≥2 months could switch to Q2W as maintenance. To reduce the risk of cytokine release syndrome (CRS), 1 to 3 priming doses were included in the study design.

A total of 39 patients were enrolled in this phase in China and Australia, with a dose range of 0.1 μg/kg to 800 μg/kg. The median age of patients was 62 years (range: 40-79), 64.1% of whom were classified as high-risk per mSMART criteria, and 46.2% had ≥1 EMD. The median number of prior lines of therapy was 4 (range: 1-10). All patients had received at least three classes of drugs (PI, IMiD, and anti-CD38 antibody), 51.3% had received at least five classes of drugs (at least 2 PIs, 2 IMiDs, and 1 anti-CD38 antibody), 41% had previously received anti-BCMA and/or anti-GPRC5D therapies, and 76.9% were refractory to the last treatment. As of the data cutoff date, November 7, 2025, the median follow-up duration was 3.25 months (range: 0.4-7.4), and the median treatment duration was 12.14 weeks (range: 1.0-33.0).

Manageable Safety Profile of IBI3003 in R/R MM Patients

Dose-limiting toxicity (DLT) only occurred in 2 patients, both of whom experienced Grade 4 platelet count decreased and recovered.
97.4% of patients experienced treatment-emergent adverse events (TEAEs). Common TEAEs included CRS, neutrophil count decrease, anemia, lymphocyte count decrease, white blood cell count decrease, and platelet count decrease.
Hematological disorders were the most common Grade ≥3 TEAEs that mainly occurred during step-up dosing and were manageable and recoverable.
The incidences of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were 64.1% and 6.1%, respectively, all of which were Grade 1-2 and resolved with treatment. Prophylactic use of tocilizumab may reduce incidence, severity, and duration CRS.
The incidence of all-grade infections was 48.7%, with Grade ≥3 infections reported in 28.2% of patients.
For GPRC5D target-related TEAEs involving the oral cavity, skin, and nails, no Grade ≥3 oral TEAEs were observed. Most skin and nail TEAEs were Grade 1-2, with only 2 patients experiencing Grade 3 rash.
Encouraging Efficacy and Depth of Response Observed with IBI3003 at Doses ≥120 μg/kg

Encouraging efficacy was observed with a median follow-up of 3.25 months: Among patients treated with ≥120 μg/kg (n=24), the overall response rate (ORR) was 83.3%, including 4 cases of stringent complete response (sCR), 7 cases of very good partial response (VGPR), and 9 cases of partial response (PR).
Among patients treated with ≥120 μg/kg, the ORR was 80% in 10 patients with EMD and 77.8% in 9 patients who had previously received anti-BCMA and/or anti-GPRC5D therapies.
Among patients who achieved CR or better as assessed by central laboratory next-generation sequencing (NGS) testing, the minimal residual disease (MRD) negativity rate was 100% (n=4).
Potent and Sustained Pharmacodynamic Responses Observed with IBI3003 in R/R MM Patients

Biomarker analysis showed that baseline soluble BCMA (sBCMA) levels were high and variable in R/R MM patients (median level: 198 ng/mL, range: 10-3010 ng/mL).
A profound and durable decline in serum sBCMA across 120, 360 and 540 μg/kg groups was observed, demonstrating a strong pharmacodynamic response.
IBI3003 has demonstrated favorable tolerability and a manageable safety profile in R/R MM patients, with encouraging efficacy signals observed at doses ≥120 μg/kg. Efficacy responses were also observed in high-risk patients, including those with EMD or prior anti-BCMA and/or anti-GPRC5D therapies. Current follow-up remains relatively short, and deeper anti-tumor responses are expected with continued treatment and observation. Dose optimization for IBI3003 is ongoing in the Phase 1 study.

Professor Peng Liu, Zhongshan Hospital Affiliated to Fudan University, stated, "Patients with R/R MM have a poor prognosis after failing standard treatments, including PI, IMiD, and anti-CD38 therapies, with an ORR of only 29.8%, a median progression-free survival of 4.6 months, and a median overall survival of 12.4 months[1]. Therefore, there is an urgent unmet clinical need for these patients, particularly those with high-risk features such as EMD or prior anti-BCMA and/or anti-GPRC5D therapies. The dual-target coverage of BCMA and GPRC5D by IBI3003 addresses the issues of antigen expression heterogeneity and treatment resistance associated with single-target drugs, reducing tumor escape. Meanwhile, its optimized CD3 affinity enables precise T-cell activation for tumor killing while also improving safety. In the disclosed Phase 1 study results, IBI3003 showed a manageable safety profile and impressive efficacy data at doses ≥120 μg/kg, with an ORR of 83.3%. It also demonstrated significant efficacy in high-risk patients with EMD or prior anti-BCMA and/or anti-GPRC5D therapies, fully reflecting its potential in overcoming R/R MM. We look forward to the long-term follow-up survival data with continuous IBI3003 treatment."

About IBI3003 (Anti-GPRC5D/BCMA/CD3 Trispecific Antibody)

IBI3003 is a tri-specific TCE developed using Innovent’s proprietary Sanbody platform to target both GPRC5D and BCMA. Designed to overcome drug resistance driven by single-antigen tumor escape, IBI3003 has exhibited superior in vivo antitumor activity in preclinical studies compared with marketed benchmark TCEs, especially in cell models with low BCMA and GPRC5D expression. Innovent is currently conducting a Phase 1/2 clinical trial (NCT06083207) of IBI3003 in China and Australia to evaluate its safety, tolerability, and efficacy in patients with R/R MM.

(Press release, Innovent Biologics, DEC 7, 2025, View Source [SID1234661219])

Median PFS Trending Beyond One Year: Leads Biolabs’ LBL-034 Showcases Breakthrough Clinical Data in Oral Presentation at the 2025 ASH Annual Meeting

On December 7, 2025 Nanjing Leads Biolabs Co., Ltd. ("Leads Biolabs" or the "Company", Stock Code: 9887.HK) reproted an oral presentation on the opening day of the conference featuring the Phase I/II clinical results of LBL-034, a GPRC5D/CD3 bispecific antibody with a unique 2:1 structure and conditional activation, independently developed using the proprietary LeadsBody platform, for the treatment of relapsed/refractory multiple myeloma (RRMM) at the 67th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") held in Orlando, Florida, USA.

The study, led by Professor Jin Lu of Peking University People’s Hospital and conducted across 17 centers in China, demonstrated that LBL-034 achieved favorable safety and highly encouraging anti-tumor activity, including in high-risk refractory subgroups, highlighting its potential as a best-in-class therapeutic candidate.

The key clinical highlights of LBL-034

Safe escalation to 1200 μg/kg with no DLTs or MTD reached.
Adverse events impacting quality of life were predominantly Grade 1–2 and occurred mainly during Cycle 1, with markedly lower incidence thereafter. Taste, skin, and nail toxicities were infrequent and generally self-resolving.
Strong efficacy across dose levels 400–1200 μg/kg (n=40).
ORR reached 82.5%, with ≥CR at 52.5%, ≥VGPR at 72.5%, and MRD negativity at 80.0%.
At 800 μg/kg, ORR and ≥CR were 90.9% and 63.6%, respectively.
Robust activity in difficult-to-treat RRMM subgroups.
Extramedullary disease (EMD): ORR 75.0%, including two sCRs. At 1200 μg/kg, ORR in EMD patients reached 100%, with rapid EMD lesion regression observed.
Prior BCMA-treated patients: ORR 85.7%, with CR/sCR 57.1%.
Durable clinical benefit.
Across the 400–1200 μg/kg range, the 12-month PFS rate was 61.2% (median follow-up: 9.6 months). At 400 μg/kg (n=11), median follow-up reached 13.1 months, with a 12-month PFS rate of 56.8%.
Executive Commentary

Dr. Charles Cai, Chief Medical Officer of Leads Biolabs, stated:

"We are delighted that the strong efficacy and clinical potential of LBL-034 have been recognized by the international scientific community. A Phase II trial evaluating the safety and efficacy of LBL-034 with a RP2D at 1200 μg/kg in 4 populations, including 4L+RRMM, 2L+RRMM with EMD, 4L+RRMM with prior BCMA therapy, and R/R Plasma Cell Leukopenia (PCL) is currently ongoing. With our focused and efficient clinical development strategy, we aim to deliver new treatment options to patients with multiple myeloma, particularly those who are refractory or have extramedullary disease, as quickly as possible."

About LBL-034

LBL-034 is a bispecific T-cell engager (TCE) that targets both GPRC5D and CD3, developed using the Company’s proprietary LeadsBody platform. Designed with a 2:1 binding format—two sites for GPRC5D and one for CD3—LBL-034 can selectively target GPRC5D+ cancer cells, conditionally activate T cells, reduce the risk of cytokine release, minimize the risk of systemic toxicity, and lower the risk of T cell exhaustion, thereby exerting anti-tumor effects in an efficient, low-toxic, and long-term stable manner.

In preclinical studies, LBL-034 has demonstrated strong efficacy signals, comparable to or exceeding those of leading competitors. The molecule is currently being evaluated in a Phase I/II clinical trial for relapsed or refractory multiple myeloma (RRMM) in China. According to Frost & Sullivan, as of November 2024, LBL-034 is the second most clinically advanced GPRC5D-targeted CD3 T-cell engager globally. In October 2024, LBL-034 received Orphan Drug Designation (ODD) from the U.S. FDA for the treatment of multiple myeloma.

(Press release, Nanjing Leads Biolabs, DEC 7, 2025, View Source [SID1234661218])