Diversity of Immune Cell Engagement and Indications across Hematologic and Solid Tumors

ASSETS DESCRIPTION INDICATION
PRODUCTS
PRECLINICAL PHASE 1 PHASE 2 PHASE 3
STATUS

ISB 1442

CD38 x CD47 BEAT® bispecific antibody
Multiple Myeloma;
AML planned in 2024​
NCT05427812
PHASE 1
ORPHAN DRUG

ISB 2001

BCMA x CD38 x CD3
TREAT™ trispecific antibody​

Multiple Myeloma
NCT05862012
PHASE 1
ORPHAN DRUG

ISB 1342

CD38 x CD3 BEAT® bispecific antibody

Multiple Myeloma T-ALL under consideration

Rectangle 4586
PHASE 1
ORPHAN DRUG

GRC 54276

Hematopoietic progenitor kinase 1 inhibitor

Solid Tumors

NCT05878691

PHASE 1

PRODUCTS

COMPOUND
ISB 1442

TARGET
CD38 x CD47 BEAT® bispecific antibody

INDICATION
Multiple Myeloma; AML planned in 2024

PHASE

NCT05427812

STATUS :
PHASE 1 ORPHAN DRUG

PRODUCTS

COMPOUND
ISB 2001

TARGET
BCMA x CD38 x CD3 TREATTM trispecific antibody​

INDICATION
Multiple Myeloma

PHASE

NCT05862012

STATUS : 
PHASE 1 ORPHAN DRUG

PRODUCTS

COMPOUND
ISB 1342

TARGET
CD38 x CD3 BEAT® bispecific antibody

INDICATION
Multiple Myeloma T-ALL under consideration

PHASE

Rectangle 4586

STATUS : 
PHASE 1 ORPHAN DRUG

PRODUCTS

COMPOUND
GRC 54276 

TARGET
Hematopoietic progenitor kinase 1 inhibitor

INDICATION
Solid Tumors

PHASE

NCT05878691

STATUS : 
PHASE 1

ISB 1442 - Triple Mechanism of Tumor-Cell Killing
Enhanced ADCP, ADCC and CDC

KEY ATTRIBUTES
  • Dual binding to CD38 and CD47 epitopes, increasing avidity relative to daratumumab

  • Two Fab regions drive binding to distinct CD38 epitopes that don’t compete functionally with daratumumab

  • One arm blocks CD47-SIRPa binding on tumor cells to enhance ADCP
    • Enhanced phagocytosis by blocking CD47 and increasing activation signaling through FcγR binding
    • CD47 is over-expressed by hematologic tumors and associated with worse prognosis
    • Reduced potential for antigen sink with lower-affinity Fab binding to CD47 expressed on healthy cells

  • Potent ADCC, CDC and ADCP based on optimized affinity, architecture/avidity and enhanced 
Fc function

  • Optimized tolerability with low potential for adverse effects on red blood cells such as hemagglutination, platelet aggregation

  • ISB 1442 was granted Orphan Drug Designation for Multiple Myeloma by the U.S. FDA
tumor cell

TREAT™: Trispecific Engagement by Antibodies based on the TCR, MHC: Major histocompatibility complex, CDC: Complement-Dependent Cytotoxicity ADCC: Antibody-Dependent Cell-mediated Cytotoxicity

ISB 2001 is first TREATTM Trispecific Antibody for
Relapsed/Refractory Multiple Myeloma

KEY ATTRIBUTES
  • BCMA and CD38 are expressed on the surface of multiple myeloma cells 
and are clinically validated targets.

  • ISB 2001 combines three proprietary Fab arms binding to CD3 on T-cells, and to BCMA and CD38 on myeloma cells.

  • In vitro studies showed increased killing potency of tumor cells compared to all tested antibodies, including currently approved and investigational multiple myeloma therapies.

  • In vivo studies in multiple myeloma models also show superior potency relative to antibodies for the treatment of multiple myeloma.

  • ISB 2001 redirects CD3+ T lymphocytes to kill tumor cells expressing from low 

    to high levels of both BCMA and CD38.

  • With two different tumor-associated antigens, ISB 2001 is expected to be more resistant to antigen escape associated with treatment of MM patients
    .
  • ISB 2001 was granted ODD by the U.S. FDA
isb2001_new
TREAT™: Trispecific Engagement by Antibodies based on the TCR MHC: Major histocompatibility complex, CDC: Complement-Dependent Cytotoxicity ADCC: Antibody-Dependent Cell-mediated Cytotoxicity

GRC 54276 - HPK1 inhibitor known to activate APCs and T-cells

  • GRC 54276 (HPK1 Inhibitor) is being developed as an orally administered IO-adjuvant treatment for patients with solid tumors. Hematopoietic progenitor kinase 1 (HPK1), is a negative regulator of T and B cell receptor signalling and an attractive therapeutic strategy for immuno-oncology based
    treatment in cancers.

  • GRC 54276 is a novel, orally active HPK1 inhibitor that demonstrates excellent stand-alone efficacy and enhances current immunotherapy efficacy.

  • In vitro, it has shown to potentiate cytokine release from DC and T-cells. It reverses Adenosine and PGE2 mediated immuno suppression.

  • In vivo (murine colon cancer efficacy model) it inhibits tumor growth of 55% at the ED max of 30 mg/kg and of 75% in combination with CTLA4 antibody. Immune profile in GRC 54276 treated tumors showed increased IL-2 and IFNg levels along with cytotoxic T cells. It also inhibit pSLP76 (ser 376) with ED50 of 11.3 mg/kg.

  • GRC 54276 is in development for advanced solid tumors
grc54276

AML: Acute Myeloid Leukemia
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