ABBV-2001 / Glenmark, AbbVie, Ichnos Glenmark Innovation - LARVOL DELTA

AbbVie advances ABBV-2001/ISB 2001: A unique, single-molecule trispecific T-cell engager (TCE) approach toward robust anti-myeloma activity with superior tumor cytotoxicity (IMS 2026) - No abstract available

Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology

First Results of a Phase 1, First-in-Human, Dose Escalation Study of ISB 2001, a BCMAxCD38xCD3 Targeting Trispecific Antibody in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) (ASH 2024) - P1 | "Tocilizumab was used in 3 patients. Sustained objective responses were demonstrated from 50μg/kg (MRD neg, sCR) in pts with heavily pre-treated RRMM, with a high ORR of 75% across dose levels. Dose-escalation continues with no DLT observed thus far (NCT05862012)."

Clinical • First-in-human • IO biomarker • P1 data • Trispecific • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Oncology • Respiratory Diseases

AbbVie to Present Phase 3 Etentamig Results and Data from Broad Multiple Myeloma Portfolio at the 2026 International Myeloma Society (IMS) Meeting (PRNewswire) - "Plenary presentation will feature Phase 3 CERVINO results demonstrating that etentamig met the study's dual primary endpoints of objective response rate (ORR) and progression-free survival (PFS) in relapsed/refractory multiple myeloma (RRMM); Additional presentations highlight research across the breadth of AbbVie's multiple myeloma portfolio, including ABBV-2001 (ISB 2001), a trispecific T-cell engager and surzetoclax, a BCL-2 inhibitor, and combination approaches....Additional presentations from these investigational assets will explore treatment sequencing, infection-related healthcare utilization and costs, and real-world outcomes, reinforcing AbbVie's strategy to advance understanding of disease heterogeneity, mechanisms of resistance and the evolving needs of patients living with multiple myeloma."

Clinical data • P1/2 data • P3 data • Multiple Myeloma

Pharmacokinetics (PK) and pharmacodynamics (PD) of ISB 2001, a novel BCMAxCD38xCD3 trispecific antibody from the first-in-human (FIH) phase 1 study in relapsed/refractory multiple myeloma patients (AACR 2025) - P1 | "ISB 2001, a novel BCMAxCD38xCD3 trispecific antibody demonstrated dose proportional PK and a high ORR across a range of dose levels in patients with heavily pre-treated RRMM, including patients previously treated with T-cell-directed therapies. Biomarker observations to date support the tumor-directed specificity of the mechanism of action and are consistent with the mild to moderate immune-related toxicity in clinic. Dose-escalation continues with no DLT observed thus far (NCT05862012)."

Clinical • First-in-human • IO biomarker • P1 data • PK/PD data • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology • CD4 • CD8 • CXCL8 • HAVCR2 • IL10 • IL2RA • IL6 • LAG3 • PD-1 • TNFRSF9

Phase 1, first-in-human study of ISB 2001: A BCMAxCD38xCD3-targeting trispecific antibody for patients with relapsed/refractory multiple myeloma (RRMM)—Dose escalation (DE) results. (ASCO 2025) - P1 | "ISB 2001 was well tolerated with manageable CRS, no ICANS and demonstrated robust anti-myeloma activity in heavily pretreated RRMM pts (NCT05862012). Full clinical data, including PK and PD results from the dose-escalation portion of the study, will be presented at the conference."

Clinical • P1 data • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology

TRIgnite- 1Study, Phase 1, First-in-Human Study of ISB 2001: A BCMAxCD38xCD3-Targeting Trispecific Antibody for Patients with Relapsed/Refractory Multiple Myeloma (RRMM)—Dose Escalation (DE) Results (IMS 2025) - P1 | "ISB 2001 was well tolerated with manageable adverse events and demonstrated robust anti-myeloma activity in heavily pretreated RRMM pts (NCT05862012). Expansion Cohorts to further optimize dose and treatment schedules following FDA Project Optimus are open to accrual."

Clinical • First-in-human • P1 data • Trispecific • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia

A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-specific Antibodies Intravenously (IV)/Subcutaneously (SC) Alone or in Combinations (clinicaltrials.gov) - P1/2 | N=602 | Recruiting | Sponsor: AbbVie | N=440 ➔ 602 | Trial completion date: Mar 2036 ➔ Dec 2035

Adverse events • Enrollment change • Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Clinical Validation of a QSP Model for ISB 2001, a Trispecific T Cell Engager to Support Optimal FIH Study Design in RRMM Patients. (PubMed, Clin Pharmacol Ther) - P1 | "This approach is consistent with the emerging FDA roadmap to reduce animal testing by utilizing computational modeling methodologies for FIH dose selection. Finally, we demonstrate the validation of the QSP model and approach by comparing its predictions with evolving preliminary safety, PK, and antimyeloma activity data from the ongoing TRIgnite-1 clinical trial."

First-in-human • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma (TRIgnite-1) (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Ichnos Sciences SA | N=85 ➔ 200

Enrollment change • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

ISB 2001, a BCMA and CD38 dual targeting T cell engager, demonstrates superior cytotoxicity relative to teclistamab in the samples of patient relapsing from CD38 and BCMA targeted immunotherapies (AACR 2024) - P1 | "In relapsed/refractory (r/r) patients, which received CD38 targeted therapy, daratumumab cytotoxicity was substantially reduced due to low CD38 expression. Blood 128, 12 (2016). (https://doi.org/10.1182/blood-2022-159353) Abstract# 3396 , ASH 2023, Hanlon Sia at al."

Clinical • First-in-human • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

Clinical validation of a quantitative systems pharmacology (QSP) model of ISB 2001 used for deriving first in human (FIH) dose and efficient phase 1 dose escalation design in relapsed refractory multiple myeloma (RRMM) patients (AACR 2025) - P1 | "This QSP model was benchmarked with teclistamab's clinical data to derive the minimal pharmacologically active dose (MPAD) of ISB 2001[1]. Despite the absence of monkey PK and toxicology data, this QSP-guided approach successfully predicted an optimal FIH dose, clinical PK, safety, and efficacy, while minimizing patient exposure to non-therapeutic doses. With this method, TCEs can be optimized solely for activity against human tumors without requiring cross-reactivity to animal species. Overall, the QSP based FIH calculation approach offers an effective pathway for designing phase 1 studies for future TCEs."

Clinical • First-in-human • IO biomarker • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma (TRIgnite-1) (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Ichnos Sciences SA | N=80 ➔ 200

Enrollment change • First-in-human • Hematological Malignancies • Multiple Myeloma • Oncology

Dual-antigen-targeting T-cell immunotherapies in MM: circumventing tumor heterogeneity and preventing antigen escape. (PubMed, Blood) - "Notably, the efficacy of the combination of teclistamab and talquetamab appears to have enhanced anti-MM activity, compared to the corresponding conventional BsAbs alone in similar patient populations. Furthermore, dual-antigen targeting with T-cell redirecting trispecific antibodies (e.g., ramantamig [BCMAxGPRC5D] and ISB2001 [BCMAxCD38]) has already demonstrated promising results in heavily pretreated MM with several studies ongoing in earlier stages of the disease. Studies with limited numbers of patients have demonstrated that CAR T-cell products with specificity for more than one antigen are also effective in advanced MM, but at this time none of the dual-targeting CAR T-cell products is clearly superior to targeting BCMA alone with ciltacabtagene autoleucel (cilta-cel). Dual-targeting should eventually be compared in large phase 3 trials with the classical approach of serial treatment with mono-targeting agents with target switch."

Heterogeneity • IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Current landscape and future prospects of bispecific antibodies in multiple myeloma. (PubMed, J Egypt Natl Canc Inst) - "The recent FDA approvals of teclistamab, talquetamab, elranatamab and linvoseltamab have reshaped the therapeutic landscape of relapsed/refractory MM (RRMM), achieving overall response rates (ORR) exceeding 60% in heavily pretreated patients...In addition to these milestones, early-phase data from emerging trispecific antibodies, such as ISB 2001, show ORRs as high as 75% and deep responses, including stringent complete responses (sCR) and minimal residual disease (MRD) negativity...We synthesize the latest clinical trial data, explore strategies for overcoming resistance, and discuss ongoing efforts to optimize combination regimens and sequencing. By critically evaluating these advancements, we highlight the evolving role of BsAbs and trispecific antibodies in redefining treatment paradigms, with the ultimate goal of improving patient outcomes and advancing toward a potential cure for multiple myeloma."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Integrated Preclinical Data Analysis of ISB 2001 Enables Optimal Starting Dose Selection for a First-in-Class Trispecific T Cell Engager Phase1 Study in Multiple Myeloma (ASH 2023) - P1 | "Instead, we generated datasets employing in vitro and in vivo models for ISB 2001 and teclistamab (possessing a similar mode of action). However, to our knowledge this is the first time that a starting dose in clinical studies of a trispecific TCE, lacking species cross-reactivity and therefore a GLP toxicology preclinical package, has been derived based on integrated preclinical data analysis utilizing a QSP model. Clinical evaluation of ISB 2001 is ongoing in a phase I dose escalation and dose expansion study in subjects with relapsed/refractory MM (NCT05862012)."

IO biomarker • P1 data • Preclinical • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology • CD38

ISB 2001: Accelerating Patient Benefits through Quantitative Systems Pharmacology (QSP) Guided First-in-Human (FIH) Starting Dose Selection (ASH 2024) - P1 | "Recently approved BCMA-TCEs, elranatamab and teclistamab, also started at low FIH doses, 0.1 to 0.3 µg/kg, respectively, requiring dose-escalation of approximately 2,150-fold and 100-fold before showing clinical response; further 10,000-fold and 5,000-fold to reach recommended phase 2 dose (RP2D) (Usmani SZ et al., Lancet. The PK profiles of ISB 2001 were available in 6 patients up to 150 µg/kg. The individual subject serum concentration-time profiles were very close to the simulated serum concentration profiles from the QSP modeling, demonstrating the accuracy of this approach.Conclusion : Given the technological advancement and tremendous improvement in designing safer TCEs, we believe our novel approach of selecting the FIH dose based on MPAD, as well as dose escalation steps based on QSP modeling is a much more efficient, faster, more patient-centric and safer path forward for developing TCEs, as compared to traditional MABEL-based approaches."

Clinical • First-in-human • IO biomarker • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

A Phase 1, First-in-Human, Dose Escalation and Dose-Expansion Study of a BCMAxCD38xCD3 Targeting Trispecific Antibody ISB 2001 in Subjects with Relapsed/Refractory Multiple Myeloma (ASH 2023) - P1 | "ISB 2001 has been designed to overcome those resistance mechanisms inherent to current MM therapies such as monoclonal antibodies (e.g. daratumumab), BCMA-targeted therapies, proteasome inhibitors(PIs), or immunomodulatory drugs(IMiDs)...The first-in-human dose was derived by integrating both in vitro and in vivo preclinical data benchmarked to teclistamab utilizing a quantitative systems pharmacology (QSP) model guided approach...A total of approximately 40 evaluable patients will be enrolled in Part 2. The study is currently open for enrollment (Clinicaltrials.gov identifier: NCT05862012)."

Clinical • First-in-human • IO biomarker • P1 data • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology

Pharmacokinetics (PK) and pharmacodynamics (PD) of ISB 2001, a BCMAxCD38xCD3 trispecific antibody, in TRIgnite-1, the First-in-Human (FIH) Phase 1 study in relapsed/refractory multiple myeloma (RRMM) (SITC 2025) - "Serum levels of APRIL (left) and BAFF (right) were determined by bead-based immunoassay; Tmax data represents the highest measured value for each patient. Plots represent data from patients who achieved an objective response"

First-in-human • IO biomarker • P1 data • PK/PD data • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology • CXCL11 • CXCL8 • HAVCR2 • IL10 • IL2RA • IL6 • LAG3 • PD-1 • TNFRSF9

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

Ichnos Glenmark Innovation receives upfront payment of USD700 million (Business Standard) - "The payment is in accordance with the agreed contractual terms and is being made towards an exclusive global licensing agreement for IGI's lead investigational asset, ISB 2001 across North America, Europe, Japan, and Greater China markets."

Financing • Multiple Myeloma

AbbVie and Ichnos Glenmark Innovation (IGI) Announce Exclusive Global Licensing Agreement for ISB 2001, a First-in-Class CD38×BCMA×CD3 Trispecific Antibody (PRNewswire) - "AbbVie...and IGI Therapeutics SA...announced an exclusive licensing agreement for IGI's lead investigational asset, ISB 2001, developed using IGI's proprietary BEAT protein platform, for oncology and autoimmune diseases...Under the terms of the agreement, AbbVie will receive exclusive rights to develop, manufacture, and commercialize ISB 2001 across North America, Europe, Japan and Greater China. Subject to regulatory clearance, IGI will receive an upfront payment of $700 million and is eligible to receive up to $1.225 billion in development, regulatory, and commercial milestone payments, along with tiered, double-digit royalties on net sales."

Licensing / partnership • Multiple Myeloma

Emerging therapeutic agents in multiple myeloma: highlights from the 2024 ASH annual meeting. (PubMed, Biomark Res) - "Key updates include: Cevostamab (FcRH5×CD3) demonstrated a 30.2% overall response rate in patients who underwent BCMA-targeted treatment and 60.6% in BCMA-targeted naïve patients;the triple-step dosing strategy reduced cytokine release syndrome. Lisaftoclax (APG-2575, BCL-2 inhibitor) displayed overall response rates ranging from 61.3 to 100% and ≥ VGPR rates of 32.3-100%, supporting enhanced response depth with favorable safety in combination regimens. Inobrodib (CCS1477, p300/CBP inhibitor) plus lenalidomide achieved a 71% overall response rate in pomalidomide-refractory patients, marking the first oral epigenetic modulator to reverse immunomodulatory drug resistance. Elranatamab (ELRA, BCMA×CD3) combined with carfilzomib and dexamethasone yielded an 83.3% overall response rate with a median duration of response not reached. Mezigdomide (MEZI, CELMoD) showed an 85.7% overall response rate and 17.5-month progression-free survival in..."

Journal • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

PHASE 1, FIRST-IN-HUMAN STUDY OF ISB 2001: A BCMAXCD38XCD3-TARGETING TRISPECIFIC ANTIBODY FOR PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)—DOSE ESCALATION (DE) RESULTS. (EHA 2025) - P1 | "ISB 2001 was well tolerated with manageable CRS, no ICANS and demonstrated robust anti-myeloma activity in heavily pretreated RRMM pts (NCT05862012). Full clinical data, including PK and PD results from the dose-escalation portion of the study, will be presented at the conference."

Clinical • P1 data • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology

Glenmark Pharma arm’s new cancer drug shows promise for relapsed multiple myeloma treatment (CNBC-TV18) - P1 | N=80 | TRIgnite-1 (NCT05862012) | Sponsor: Ichnos Sciences SA | "The drug showed an overall response rate of 79% in patients who received the recommended dose, meaning nearly four out of five patients saw their cancer shrink. One in three patients achieved a complete or near-complete response. Importantly, these results were seen even in patients who had previously tried and failed other advanced treatments, such as CAR-T cell therapy and bispecific antibodies."

P1 data • Multiple Myeloma

Full Dose-Escalation Data Show Continued High Response Rates and Favorable Safety Profile of ISB 2001, a First-in-Class BCMA × CD38 × CD3 Trispecific Antibody, for the Treatment of Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - P1 | N=80 | NCT05862012 | Sponsor: Ichnos Sciences SA | "Ichnos Glenmark...presented promising full dose-escalation results from its Phase 1 TRIgnite-1 study of ISB 2001, an investigational first-in-class BCMA × CD38 × CD3-targeting trispecific antibody for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). These data, presented as a rapid oral presentation (Abstract #7514) at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, demonstrated a sustained overall response rate (ORR) of 79% and a high complete/stringent complete response (CR/sCR) rate of 30% across seven active dose levels (≥ 50 µg/kg) in a heavily pretreated patient population, with a favorable safety profile. The ORR was 74% in all treated patients, including two patients treated at lower dose levels....The median half-life of ISB 2001 was approximately 17 days, supporting the potential for less-frequent dosing."

P1 data • PK/PD data • Multiple Myeloma