ISB 1342 / Glenmark - LARVOL DELTA

A population-based gap analysis of bispecific antibody trial access: Racial, geographic, and Medicaid-linked disparities in lymphoma and myeloma (ASH 2025) - P1/2, P2 | "We calculated trial-site density per 1,000 incidentcases in each state and used logistic regression to estimate odds of a county hosting a bsAb trialsite based on racial/ethnic majority, rurality, and Medicaid metrics, adjusting for local incidencerates. We identified 127 unique U.S. bsAb trial sites for DLBCL and MM, including representativetrials such as NCT04649359, NCT04824794, and ISB-1342 studies. This is the first quantitative, population-based analysis showing that bsAb trial accessfor DLBCL and MM is significantly skewed toward urban, high‑income, majority‑White countieswith higher Medicaid-managed care penetration and located in Medicaid-expansion states.Disadvantaged counties (majority‑Black/Hispanic, rural, lower Medicaid reach) are dramaticallyunderrepresented. Given that bsAbs like epcoritamab and elranatamab were FDA approved in2023, this contemporary gap risks perpetuating inequities in access to cutting-edgeimmunotherapies. These disparities..."

Clinical • Medicaid • Reimbursement • US reimbursement • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • CD20

Dose Escalation of ISB 1342, a Novel CD38xCD3 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma (RRMM) (ASH 2023) - P1 | "This mechanism of action is different from existing monospecific CD38 targeting therapies and was designed to overcome resistance to daratumumab in MM. Treatment with ISB 1342 was well tolerated at higher dose levels evaluated. Observed CRS events were moderate. No increased risk of infection has been observed ."

Clinical • IO biomarker • Anemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • CD4 • CD69 • CD8 • IFNG • IL10 • IL2 • IL6 • TNFA

Study of ISB 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma (clinicaltrials.gov) - P1 | N=81 | Completed | Sponsor: Ichnos Sciences SA | Recruiting ➔ Completed | N=245 ➔ 81 | Trial completion date: May 2024 ➔ Dec 2023

Enrollment change • Trial completion • Trial completion date • 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

ICHNOS SCIENCES DELIVERS STRONG EVIDENCE FOR ITS TRIO OF ONCOLOGY ASSETS AT ASH 2023 ANNUAL MEETING (PRNewswire) - P1 | N=245 | NCT03309111 | Sponsor: Ichnos Sciences SA | "Dose-dependent pharmacokinetics and biomarkers: Following IV infusion, ISB 1342 showed dose-linear increase in serum exposures across the evaluated dose range. Increases in several T-cell activation-related biomarkers (CD69 by flow, and serum cytokines withing 24hrs, such as IFNg, TNFa, IL-2, IL-6 and IL-10), were consistently observed following ISB 1342 dosing supporting proof of mechanism. Efficacy signals: Positive results in patient groups at higher dose levels (8 and 16 μg/kg cohorts) align with predicted effectiveness based on a sophisticated preclinical quantitative system pharmacology (QSP) model, supporting the drug's potential success in treating multiple myeloma."

P1 data • 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

Preclinical Characterization of ISB 1342, a CD38 × CD3 T-Cell Engager for Relapsed/Refractory Multiple Myeloma (Cancer Network) - "A recent publication characterizing ISB 1342, a CD38/CD3 bispecific antibody, has demonstrated its safety and efficacy against multiple myeloma (MM) in animal models....Using a redirected lysis (RDL) assay with human peripheral blood mononuclear cells (hPBMCs) as effectors, in vitro studies showed that ISB 1342 engaged CD38 on tumor cells and CD3ε on T cells, mediating T-cell activation and killing of tumor cells. Additionally, the potency of ISB 1342 was not influenced by the presence of daratumumab in sequential or concomitant treatment."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

Preclinical Characterization of ISB 1342, a CD38 × CD3 T-Cell Engager for Relapsed/Refractory Multiple Myeloma (Cancer Network) - "A recent publication characterizing ISB 1342, a CD38/CD3 bispecific antibody, has demonstrated its safety and efficacy against multiple myeloma (MM) in animal models....In NSG mice engrafted subcutaneously with KMS-12-BM (MM cell line) and injected intraperitoneally with hPBMCs, ISB 1342 showed the ability to control tumor growth and increase the infiltration of T cells in the tumor microenvironment, irrespective of CD38 expression levels. In terms of safety, ISB 1342 exhibited an adequate profile in PK/PD studies, highlighting a potential therapeutic window. Overall, ISB 1342 has shown potential as an effective and safe therapy for multiple myeloma patients, even in those previously treated with daratumumab."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

Pre-clinical characterization of ISB 1342, a CD38xCD3 T-cell engager for relapsed/refractory multiple myeloma. (PubMed, Blood) - "Whilst treatment of multiple myeloma (MM) with daratumumab significantly extend patient lifespan, resistance to therapy is inevitable. These data suggest that ISB 1342 may be an option in patients with r/rMM refractory to prior anti-CD38 bivalent monoclonal antibody therapies. It is currently developed in a phase 1 clinical study."

Journal • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

Initial Results of Dose Escalation of ISB 1342, a Novel CD3xCD38 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma (RRMM) (ASH 2022) - P1 | "This mechanism of action is differentiated from existing monospecific CD38 targeting therapies and was designed to overcome resistance to daratumumab in MM. Treatment with ISB 1342 was well tolerated at the dose levels evaluated. The observed CRS events were moderate. Dose escalation continues with additional dose cohorts accruing."

Clinical • IO biomarker • Anemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Multiple Myeloma • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia • IFNG • IL10 • IL2 • IL6 • TNFA

ICHNOS SCIENCES PRESENTS DATA SUPPORTING THREE ONCOLOGY ASSETS AT ASH 2022 ANNUAL MEETING (PRNewswire) - P1 | N=245 | NCT03309111 | Sponsor: Ichnos Sciences SA | "In addition to the oral presentation on trispecific antibody ISB 2001 described above, Ichnos was selected for three poster presentations of data on other pipeline assets: Initial Results of Dose Escalation of ISB 1342, a Novel CD3xCD38 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma...presented by Sanjay Mohan, MD, on Sunday, December 11: Showed that treatment with ISB 1342 was well tolerated at the evaluated Q1W dose levels up to cohort 109 (2µg/kg priming, 8µg/kg targeted dose), that observed CRS events were moderate and manageable with supportive care, and that no increased risk of infection has been observed; Dose escalation continues with participants enrolling in additional cohorts..."

Enrollment status • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

ICHNOS SCIENCES DATA SELECTED FOR PRESENTATION AT THE 64TH ASH ANNUAL MEETING (PRNewswire) - "Ichnos Sciences Inc...announced that four abstracts highlighting data on its pipeline assets have been selected for presentation at the upcoming 64th American Society of Hematology (ASH) Annual Meeting and Exposition....These abstracts highlight three assets – ISB 1342, ISB 1442 and ISB 2001 – two of which are currently in Phase 1 clinical studies in relapsed/refractory multiple myeloma."

Clinical data • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia

ICHNOS SCIENCES ANNOUNCES SELECTION OF TRISPECIFIC ANTIBODY ISB 2001 AS NEXT CLINICAL CANDIDATE FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA (PRNewswire) - "ISB 2001, is on Track to Enter Clinical Development in 2023...Ichnos Sciences Inc...announced the selection of ISB 2001, its first TREAT1 trispecific antibody, which engages BCMA x CD38 x CD3, as its next candidate to move into clinical development. The company has initiated IND-enabling studies for relapsed/refractory multiple myeloma and aims to advance ISB 2001 to a first-in-human study once clearance from the health authorities is received in 2023....A first-in-human study with ISB 1442 is planned to start in mid-2022. Ichnos' lead clinical candidate, ISB 1342, a CD38 x CD3 bispecific antibody, continues to enroll patients with relapsed/refractory multiple myeloma in an ongoing Phase 1, dose escalation and expansion study."

IND • New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

A multispecific antibody platform for optimal engineering of multiple myelomaimmunotherapies. (CIMT 2022) - P1 | "In vivo, ISB 1442 shows higher inhibition of tumor growth relative to daratumumab and comparable tumor regression relative to magrolimab. In summary, we report two novel approaches for the treatment of MM using the BEAT technology to co-target either CD38 and CD3, or CD38 and CD47. The designs of ISB 1342 and ISB 1442 are anticipated to enhance antitumor activity in MM patients by overcoming primary and acquired mechanisms of resistance."

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

[VIRTUAL] ISB 1342: A first-in-class CD38 T cell engager for the treatment of relapsed refractory multiple myeloma. (ASCO 2021) - "Hence the higher potency of ISB 1342 relative to daratumumab supports the ongoing clinical development in multiple myeloma patients."

IO biomarker • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • CXCL10 • GZMA • TNFA

Phase 1, multicenter, open-label study of single-agent bispecific antibody t-cell engager GBR 1342 in relapsed/refractory multiple myeloma. (ASCO 2018) - P1; "CD38, a transmembrane glycoprotein upregulated on myeloma cells, is a validated disease target as evidenced by the anti-myeloma activity of daratumumab, an anti-CD38 human IgG1 monoclonal antibody. Primary endpoints include AEs (frequency, severity), number of dose-limiting toxicities during Cycle 1 (Part 1), and objective response to GBR 1342 (Part 2). Secondary endpoints include pharmacokinetics and anti-tumor activity of GBR 1342 (progression-free and overall survival)."

Clinical • P1 data • Multiple Myeloma

[VIRTUAL] ISB 1342: A FIRST-IN-CLASS CD38 T CELL ENGAGER FOR THE TREATMENT OF RELAPSED REFRACTORY MULTIPLE MYELOMA (EHA 2021) - "The release of the Granzyme A and B, TNF-alpha and CXCL-10 in the tumor micro-environment one week post-treatment was strongly and significantly increased by ISB 1342 but not by daratumumab and ISB 1342_13DU; this represents a correlate of anti-tumor immunity associated with ISB 1342 efficacy in vivo. Conclusion Hence the higher potency of ISB 1342 relative to daratumumab supports the ongoing clinical development in multiple myeloma patients."

IO biomarker • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology • CXCL10 • GZMA • TNFA

Study of ISB 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma (clinicaltrials.gov) - P1; N=197; Recruiting; Sponsor: Ichnos Sciences SA; Phase classification: P1/2 ➔ P1; N=125 ➔ 197; Trial completion date: Feb 2021 ➔ May 2024; Trial primary completion date: Feb 2021 ➔ Mar 2024

Clinical • Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Ichnos Sciences Presents Preclinical Data Confirming Potential For ISB 1342 In Relapsed/Refractory Multiple Myeloma At 2021 ASCO Annual Meeting (PRNewswire) - "Ichnos' data demonstrate the ability of ISB 1342 to redirect T lymphocytes against tumor cells expressing varying levels of CD38 in preclinical in vitro and in vivo potency models. ISB 1342 engages a different epitope than do approved CD38-targeted biologics, and these models suggest that it may be effective in patients who have progressed despite treatment with such therapies."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

"1st #ASCO21 #mmsm list ⁦@mtmdphd⁩ 8007 teclistamab 8008 talquetamab 8010 NGF vs blood mass spec 8011 Elo-KRD 8013 Cartitude-2 10507 SPM in AA vs white 8029 ctDNA for MRD 8041 LocoMMotion 8044 ISB1342 CD38 8050 New MGUS/SMM mouse 12082 Prognosis perception in caregivers" (@AuclairDan)

Circulating tumor DNA • Preclinical • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma

"#ASCO21 #mmsm 18512 Disparity in MM https://t.co/1qrOPL4mq6 8029 ctDNA for MRD https://t.co/cCyCwGVuZ7 8041 LocoMMotion https://t.co/OYY2SkxkBh 8044 ISB1342 https://t.co/awcfnRi82J 8050 MGUS/SMM mouse https://t.co/3bMMvHnCQX 12082 Perception in caregivers https://t.co/53G7byeWIf" (@AuclairDan)

Circulating tumor DNA • Preclinical • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma

Study of GBR 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma (clinicaltrials.gov) - P1/2; N=125; Recruiting; Sponsor: Ichnos Sciences SA; Phase classification: P1 ➔ P1/2

Clinical • Phase classification

"#Glenmark #orphandrug #USFDA #MultipleMyeloma #gbr1342 For more precise news subscribe to pharmashots @Pharmashot https://t.co/gGoIvobme5" (@consultoctavus)

Orphan drug

Glenmark receives Orphan Drug Designation for GBR 1342, a bispecific antibody candidate under evaluation for the treatment of multiple myeloma (PRNewswire) - "Glenmark Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to its bispecific antibody candidate GBR 1342 for the treatment of patients with multiple myeloma who have received prior therapies. Derived from the company's proprietary BEAT® (Bispecific Engagement by Antibodies based on the T cell receptor) technology, GBR 1342 is being investigated for the treatment of multiple myeloma. The candidate is one of five clinical-stage assets in the pipeline of Glenmark's new innovation company."

Orphan drug

Study of GBR 1342, a CD38/CD3 Bispecific Antibody, in Subjects With Previously Treated Multiple Myeloma (clinicaltrials.gov) - P1; N=125; Recruiting; Sponsor: Glenmark Pharmaceuticals S.A.; Trial completion date: Apr 2020 ➔ Feb 2021; Trial primary completion date: Mar 2019 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date