ISB 1442 / Glenmark - LARVOL DELTA

Initial Dose Escalation of ISB 1442, a Novel CD38 Biparatopic x CD47 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma (RRMM) (ASH 2023) - P1/2 | "ISB 1442 has 2 Fab domains binding to distinct CD38 epitopes that do not compete functionally with daratumumab. Treatment with ISB 1442 was well tolerated at the dose levels evaluated. The observed clinical CRS events were moderate and potentially related to macrophage activation following ISB 1442 administration. Updated clinical, biomarker and PK data will be presented for this ongoing study."

Clinical • IO biomarker • Anemia • Dermatology • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • CD47 • SIRPA

Dose Escalation of ISB 1442, a Novel CD38 Biparatopic x CD47 Bispecific Antibody, in Patients with Relapsed / Refractory Multiple Myeloma (ASH 2024) - P1/2 | "Tocilizumab was used in 5 pts. Super-proportional PK and receptor occupancy biomarkers suggest higher dose levels may be needed to achieve required efficacy concentrations in bone marrow compartment. The study continues to enroll in the dose escalation (NCT05427812)."

Clinical • IO biomarker • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • CD47

Biparatopic binding of ISB 1442 to CD38 in trans enables increased cell antibody density and increased avidity. (PubMed, MAbs) - "The specific design and structural features of ISB 1442 enable: 1) enhanced trans binding to adjacent CD38 molecules to increase Fc density at the cancer cell surface; 2) prevention of avid cis binding to monomeric CD38 to minimize blockade by soluble shed CD38; and 3) greater binding avidity, with a slower off-rate at high CD38 density, for increased specificity. The superior CD38 targeting of ISB 1442, at both high and low receptor densities, by its biparatopic design, will enhance proximal CD47 blockade and thus counteract a major tumor escape mechanism in multiple myeloma patients."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Phase 1/2 Study of ISB 1442 in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=29 | Terminated | Sponsor: Ichnos Sciences SA | N=121 ➔ 29 | Trial completion date: May 2027 ➔ Nov 2024 | Recruiting ➔ Terminated | Trial primary completion date: May 2027 ➔ Nov 2024; Business decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

Submit Current Safety Data of Indians: CDSCO Panel Tells Glenmark On Anti-Cancer Drug ISB1442 (Medical Dialogues) - "Reviewing the Phase I/II clinical study protocol of the anti-cancer drug ISB1442 presented by the drug major Glenmark, the Subject Expert Committe (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has opined the firm to submit the current safety data including data of Indian Subjects from the already approved clinical trial in India....This came after the drug major Glenmark presented Phase I/II clinical study protocol No ISB1442-10 version 1.0 dated 16 Feb 2024."

Clinical protocol • Hematological Malignancies • Oncology

Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma. (PubMed, Nat Commun) - "ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma."

Journal • Hematological Disorders • 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) - P1/2 | N=121 | NCT05427812 | Sponsor: Ichnos Sciences SA | "Safety and tolerance: Demonstrated treatment with ISB 1442 was well tolerated at the dose levels evaluated, with observed clinical cytokine release syndrome (CRS) events being low grade and potentially related to macrophage activation following ISB 1442 administration. Dose-dependent pharmacokinetics: Showed dose-linear increase in serum concentration up to DL 3 (60 mg), followed by a super-proportional increase in serum exposure most evident between DL3 (60 mg) and DL4 (150 mg)."

P1/2 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

ICHNOS SCIENCES RECEIVES ORPHAN DRUG DESIGNATION FOR FIRST-IN-CLASS BISPECIFIC (CD38 x CD47) ANTIBODY INNATE CELL MODULATOR, ISB 1442 (PRNewswire) - "Ichnos Sciences Inc...announced the company has been granted orphan drug designation (ODD) by the U.S. Food and Drug Administration (FDA) for its first-in-class biparatopic 2+1 BEAT^® bispecific antibody targeting CD38 and CD47 for the treatment of relapsed/refractory multiple myeloma (MM). ISB 1442, which is Ichnos' second clinical-stage asset to receive ODD in MM..."

Orphan drug • Hematological Malignancies • Multiple Myeloma • Oncology

Preclinical Evaluation of ISB 1442, a First-in-Class CD38 and CD47 Bispecific Antibody Innate Cell Modulator for the Treatment of AML and T-ALL (ASH 2022) - P2 | "Preclinical activity of ISB 1442 for the treatment of relapsed/refractory multiple myeloma (rrMM), including increased killing potency relative to daratumumab and magrolimab benchmarks as well as more favorable off tumor/on target specificity, was reported previously (Sammicheli et al. In summary, these data support the clinical development of 1442 in AML and T-ALL. Based on its unique design and multiple mechanisms of action, ISB 1442 is anticipated to have antitumor activity in AML and T-ALL patients in a single antibody relative to anti-CD38 or anti-CD47 monoclonal antibodies as well as their combination."

IO biomarker • Preclinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia • CD47 • SIRPA

A Phase 1/2, First-in-Human, Multicenter, Open-Label, Dose Escalation and Dose-Expansion Study of Single-Agent ISB 1442 in Patients with Relapsed/Refractory Multiple Myeloma (ASH 2022) - P1/2 | "Hence, an enhanced CD38 targeted therapy that unleashes the innate immune cell mediated tumor killing potential and overcomes daratumumab resistance mechanisms may present a unique opportunity to treat MM...Due to low-affinity binding to CD47, ISB 1442 engages CD47 efficiently only upon CD38 binding (avidity-induced binding), thereby reducing the potential for on-target, off-tumor effects, and it does not cause any detectable RBC depletion in vitro compared to magrolimab (Figure 2)...The study is currently open for enrollment. Clinicaltrials.gov identifier: NCT05427812."

Clinical • IO biomarker • P1/2 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • CD47 • SIRPA

ICHNOS SCIENCES PRESENTS DATA SUPPORTING THREE ONCOLOGY ASSETS AT ASH 2022 ANNUAL MEETING (PRNewswire) - "Preclinical Evaluation of ISB 1442, a First-in-Class CD38 and CD47 Bispecific Antibody Innate Cell Modulator for the Treatment of AML and T-ALL...presented by Stefano Sammicheli, PhD, on Sunday, December 11: Showed that ISB 1442 induces killing of acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL) cell lines in multiple in vitro assays, and has superior activity to daratumumab in AML and T-ALL cell lines expressing intermediate or low CD38 expression; Demonstrated more frequent killing of AML blasts and a trend of higher potency compared to monospecific anti-CD38 daratumumab or anti-CD47 (5F9)...A Phase 1/2, First-in-Human, Multicenter, Open-Label, Dose Escalation and Dose-Expansion Study of Single-Agent ISB 1442 in Patients with Relapsed/Refractory Multiple Myeloma...to be presented by Tony Jiang, MD PhD on the evening of Monday, December 12: Provides an overview of the ongoing Phase 1/2 study..."

Preclinical • Trial status • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia

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

ISB 1442, a first-in-class CD38 and CD47 bispecific antibody innate cell modulator for the treatment of CD38 positive hematological malignancies (ITOC 2022) - "ISB 1442 is designed with a bi-paratopic anti-CD38 arm that strongly binds two CD38 epitopes on tumor cells which do not functionally compete with daratumumab. Conclusions We report a novel approach for the treatment for CD38 positive hematologic malignancies by co-targeting CD38 and CD47 using a first in class multispecific antibody. Based on its unique design and multiple mechanisms of action, ISB 1442 is anticipated to enhance antitumor activity in patients relative to anti-CD38 mAbs by overcoming primary and acquired tumor escape mechanisms of resistance."

Hematological Malignancies • Oncology • SIRPA

Phase 1/2 Study of ISB 1442 in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=121 | Recruiting | Sponsor: Ichnos Sciences SA | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Immune Modulation • Multiple Myeloma • Oncology

ICHNOS SCIENCES ANNOUNCES INITIATION OF FIRST-IN-HUMAN STUDY FOR ISB 1442 (PRNewswire) - "Ichnos Sciences Inc...today announced dosing of the first patient in the Phase 1/2 dose escalation and expansion study of ISB 1442, a CD38 x CD47 biparatopic bispecific antibody for the treatment of relapsed/refractory multiple myeloma....The study will enroll approximately 121 participants across sites in Australia and the United States."

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Phase 1/2 Study of ISB 1442 in Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=121 | Not yet recruiting | Sponsor: Ichnos Sciences SA

New P1/2 trial • Hematological Malignancies • Immune Modulation • Multiple Myeloma • Oncology

ISB 1442, A FIRST-IN-CLASS CD38 AND CD47 BISPECIFIC ANTIBODY INNATE CELL MODULATOR FOR THE TREATMENT OF CD38 POSITIVE HEMATOLOGICAL MALIGNANCIES (EHA 2022) - "Aims ISB 1442 was developed for the treatment of hematologic malignancies that express CD38, including multiple myeloma (MM), acute myeloid leukemia (AML), and T-acute lymphoblastic leukemia (T-ALL), with the intention of overcoming mechanisms of resistance to CD38-targeted therapies such as daratumumab and isatuximab, and minimizing hemagglutination/hemolysis on red blood cell (RBC) observed with anti-CD47 monoclonal antibodies (mAb) such as magrolimab. Conclusion In summary, we report a novel approach for the treatment for CD38 positive hematologic malignancies by co-targeting CD38 and CD47 using a first in class multispecific antibody. Based on its unique design and multiple mechanisms of action, ISB 1442 is anticipated to enhance antitumor activity in patients relative to anti-CD38 mAbs by overcoming primary and acquired tumor escape mechanisms of resistance."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia • SIRPA

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

ISB 1442, a first-in-class CD38 and CD47 bispecific antibody innate cell modulator for the treatment of CD38 positive hematologic malignancies. (CIMT 2022) - "ISB 1442 induced higher tumor growth inhibition relative to daratumumab and comparable tumor regression compared to magrolimab. In summary, we report a novel approach for the treatment of CD38 positive hematologic malignancies by co-targeting CD38 and CD47with a single agent. Based on its unique design and multiple mechanisms of action, ISB 1442 is anticipated to enhance antitumor activity in patients relative to anti-CD38 mAbs by overcoming primary and acquired tumor escape mechanisms of resistance."

Hematological Disorders • Hematological Malignancies • Oncology • SIRPA

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

"ISB 1442, a first-in-class CD38 and CD47 bispecific antibody innate cell modulator for the treatment of CD38 positive hematologic malignancies" (CIMT 2022) - No abstract available

Hematological Disorders • Hematological Malignancies • Oncology

Engineering ISB 1442, a First-in-Class 2+1 Biparatopic Multispecific Antibody that Targets both CD38 and CD47, as a Treatment for Relapsed/Refractory Multiple Myeloma and Other CD38-Positive Hematologic Malignancies (PEGS 2022) - No abstract available

Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

BEAT, a Plug-and-Play Platform for Engineering Novel Multi-Specific Antibodies Against Cancer (PEGS 2022) - "ISB 1442, a first-in-class 2+1 biparatopic BEAT® 2.0 bispecific (CD38xCD47) antibody, demonstrates higher potency and tumor growth inhibition preclinically relative to daratumumab. A Phase 1 study in hematologic malignancies is planned for mid-2022."

Hematological Disorders • Hematological Malignancies • Oncology