ISB 2001 / Glenmark - LARVOL DELTA

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 | "Clinical Trial Registration Number: NCT05862012 The abstract will be released to the public on May 22, 2025 at 4:00 PM"

Clinical • P1 data • Trispecific • Hematological Malignancies • 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

Ichnos Glenmark Innovation (IGI) Receives U.S. FDA Fast Track Designation for ISB 2001 for Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - "IGI, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for ISB 2001. This important designation was granted for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least three prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody....Results from the dose-escalation portion of the Phase 1 clinical study of ISB 2001 in patients with heavily pretreated multiple myeloma to be presented at the 2025 ASCO Annual Meeting."

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

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 • IO biomarker • P1 data • 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 • IO biomarker • P1 data • Trispecific • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Oncology • Respiratory Diseases

Ichnos Glenmark Innovation (IGI) Presents First Clinical Data from Phase 1 Study of Trispecific TREAT Antibody, ISB 2001, Showing High Overall Response Rate (ORR) with Durable Responses and Favorable Safety Profile in Patients with Heavily Pretreated Multiple Myeloma (GlobeNewswire) - P1 | N=80 | NCT05862012 | Sponsor: Ichnos Sciences SA | "No dose-limiting toxicities were observed up to weekly subcutaneous doses of 1.2 mg/kg, with mostly mild Cytokine Release Syndrome, no cases of neurotoxicity, and no discontinuations due to adverse events; ISB 2001 demonstrated an ORR of 83% in heavily pretreated patients treated at active doses (0.05 mg/kg and higher); Preliminary half-life of over 10 days supports planned evaluation of less-frequent dosing schedule; Data suggest ISB 2001 could compare favorably with approved bispecific options."

P1 data • Multiple Myeloma

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 • IO biomarker • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

Ichnos Glenmark Innovation (IGI) Announces First Presentation of Data from Phase 1 Study of the Trispecific ISB 2001 in Relapsed/Refractory Multiple Myeloma (r/rMM) at Upcoming ASH Annual Meeting (GlobeNewswire) - P1 | N=80 | NCT05862012 | Sponsor: Ichnos Sciences SA | "The oral presentation will detail results from the dose-escalation portion of the study. The abstract features data as of July 2024, including: An overall response rate (ORR) of 75% (9/12) in efficacy-evaluable patients, including one (1) MRD negative stringent complete response (sCR). A favorable safety and tolerability profile that showed no dose-limiting toxicities (DLTs), only one adverse event of special interest (AE) above Grade 2, and no treatment discontinuation. The oral presentation at ASH will be supplemented with additional data and analyses."

P1 data • Multiple Myeloma

Certara & Ichnos Glenmark Innovation Collaboration Optimizes Dosing Strategy for Potential First-In-Class Cancer Drug (GlobeNewswire) - "Certara, Inc...shared the results from its collaboration with Ichnos Glenmark Innovation (IGI) on the first-in-human dose prediction and selection for ISB 2001. Preclinical research and biosimulation findings were recently published in Nature Cancer. This publication highlighted ISB 2001’s therapeutic potential for relapsed/refractory multiple myeloma patients....IGI sought to optimize the FIH dose of ISB 2001 to maximize patient safety and efficacy....As a result of this collaboration, the clinical starting dose increased by approximately 50-100 fold over the conventional starting dose....Accepted by the U.S. FDA and Australian HREC, this approach paves the way for determining FIH dosing for ISB 2001 and other TCEs."

Preclinical • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells. (PubMed, Nat Cancer) - P1 | "Despite the broad expression of CD38 across human tissues, ISB 2001 demonstrated a reduced T cell activation profile in the absence of tumor cells when compared to TCEs targeting CD38 only. To determine an optimal first-in-human dose for the ongoing clinical trial ( NCT05862012 ), we developed an innovative quantitative systems pharmacology model leveraging preclinical data, using a minimum pharmacologically active dose approach, therefore reducing patient exposure to subefficacious doses of therapies."

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

IGI Announces Publication in Nature Cancer on ISB 2001, IGI's Innovative Trispecific Antibody for Relapsed/Refractory Multiple Myeloma (GlobeNewswire) - "Ichnos Glenmark Innovation (IGI), an alliance between Ichnos Sciences...and Glenmark Pharmaceuticals Ltd., announced today that Nature Cancer published a research article describing the preclinical development of ISB 2001, a first-in-class trispecific antibody targeting BCMA and CD38 on myeloma cells and CD3 on T cells....Article highlights preclinical findings demonstrating ISB 2001 can potentially overcome myeloma cell escape mechanisms to evade therapeutic anti-tumor activity. Data show superior killing potency of multiple myeloma tumor cells by ISB 2001 when compared to several approved bispecific therapies and combination of therapies."

Preclinical • Multiple Myeloma

Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Ichnos Sciences SA | Not yet recruiting ➔ Recruiting

Enrollment open • 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 • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology

Ichnos Glenmark Innovation Presents Preclinical Data for its Oncology Asset ISB 2001 at AACR 2024 Annual Meeting (PRNewswire) - "Ichnos Glenmark Innovation...shared preclinical data for its oncology asset ISB 2001 during the oral presentation at the annual American Association for Cancer Research (AACR) 2024....ISB 2001 showed superior cytotoxicity in comparison with teclistamab, alnuctamab and EM-801 across cell lines with variable expression levels of both BCMA and CD38. ISB 2001 showed minimal cytotoxicity reduction by soluble factors (sCD38, sBCMA, APRIL) compared to teclistamab, alnuctamab and EM-801, which exhibited cytotoxicity reduction to a much eater degree. Superior tumor growth inhibition in MM xenograft models relative to teclistamab + daratumumab combination."

Preclinical • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

Glenmark Gets CDSCO Panel Nod To study ISB 2001 In Multiple Myeloma (Medical Dialogues) - "The drug major Glenmark has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organization (CDSCO) to conduct the clinical study of the anticancer drug ISB 2001 in relapsed /refractory multiple myeloma....This came after the drug major Glenmark presented Phase I clinical study protocol No. ISB 2001-101 version 2.0 amendment 01 dated 07/April/2023. This study is a first-in-human, Phase I, Open label study that will evaluate the safety and anti-myeloma activity of ISB 2001 in participants with relapsed/refractory multiple myeloma."

Non-US regulatory • Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Ichnos and Glenmark take a collaborative leap to accelerate innovation in Cancer Treatment with their alliance - 'Ichnos Glenmark Innovation' (PRNewswire) - "This alliance brings together drug innovation capabilities of Ichnos and Glenmark to develop cutting-edge therapies for the treatment of hematological malignancies and solid tumors; IGI harnesses the collective expertise of over 150 scientists, operating through its three centers of innovation across the USA, Switzerland and India; There are currently three oncology molecules in clinical trials, with two having received orphan drug designation from the U.S. FDA; The synergies derived from this alliance will substantially reduce Glenmark's investment in innovative research."

Licensing / partnership • Acute Lymphocytic Leukemia • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

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 • IO biomarker • P1 data • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

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

1st patient dosed in Phase 1 trial of triple-target treatment ISB 2001 (Myeloma Research News) - "The first multiple myeloma patient has been dosed in a Phase 1 clinical trial evaluating the safety and efficacy of ISB 2001, Ichnos Sciences’ trispecific antibody — a treatment that simultaneously targets three proteins. This study (NCT05862012) aims to recruit up to 80 adults with relapsed or refractory (hard-to-treat) multiple myeloma at sites in Australia and the U.S. Locations in the U.S. may not yet be open."

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

ICHNOS SCIENCES DATA SELECTED FOR PRESENTATION AT THE 65TH ASH ANNUAL MEETING (PRNewswire) - "Ichnos Sciences...today announced that three abstracts highlighting data on its leading oncology assets have been selected for presentation at the upcoming 65th American Society of Hematology (ASH) Annual Meeting and Exposition. The meeting will be held December 9-12, 2023, in San Diego, California...These abstracts discuss three assets—ISB 2001, ISB 1342 and ISB 1442..."

Clinical data • Hematological Malignancies • Multiple Myeloma • Oncology

ICHNOS SCIENCES ANNOUNCES INITIATION OF FIRST-IN-HUMAN CLINICAL TRIAL FOR ISB 2001 (PRNewswire) - "Ichnos Sciences Inc...today announced dosing of the first patient in the Phase 1 first-in-human clinical trial of ISB 2001, a BCMA x CD38 x CD3 TREAT™ trispecific antibody, for the treatment of multiple myeloma....This study is a first-in-human, Phase 1, open-label study that will evaluate safety and anti-myeloma activity of ISB 2001 in an estimated 80 participants with relapsed/refractory multiple myeloma (R/R MM) across multiple centers, including the U.S. and Australia. The multicenter study will be conducted in two parts: dose escalation and dose expansion."

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

ICHNOS SCIENCES RECEIVES ORPHAN DRUG DESIGNATION FOR FIRST-IN-CLASS TRISPECIFIC ANTIBODY, ISB 2001 (PRNewswire) - "Ichnos Sciences Inc...announced it has been granted orphan drug designation (ODD) by the U.S. Food and Drug Administration (FDA) for its first-in-class T-cell engaging trispecific antibody, ISB 2001, for the treatment of multiple myeloma....This milestone is achieved as Ichnos prepares to initiate a Phase 1 first-in-human dose-escalation dose-expansion study of ISB 2001 later this summer, after securing approval from the Human Research Ethics Committee (HREC) in Australia and IND clearance from the FDA."

New P1 trial • Orphan drug • Hematological Malignancies • Multiple Myeloma • Oncology

Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=80 | Not yet recruiting | Sponsor: Ichnos Sciences SA

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Overcoming mechanisms of escape from treatments for multiple myeloma with ISB 2001, a potential first-in-class trispecific BCMA and CD38 targeted T cell engager (AACR 2023) - "We also compared the tumor killing potency of ISB 2001 to teclistamab, a BCMAxCD3 bispecific antibody recently approved to treat relapsed/refractory (RR) MM patients who have received prior lines of treatment. Significant benefit is anticipated for RRMM patients who may experience tumor escape through target downregulation mechanisms. The evaluation of ISB2001 in a phase 1 clinical trial is planned for the first half of 2023."

IO biomarker • Trispecific • Hematological Malignancies • Multiple Myeloma • Oncology