PIPELINE
Oncology
- Overview
- ISB 1442
- ISB 2001
- GRC 54276
| ASSETS | DESCRIPTION | INDICATION |
|---|---|---|
| PRODUCTS |
| PRECLINICAL | PHASE 1 | PHASE 2 | PHASE 3 |
|---|---|---|---|
| STATUS |
|---|
CD38 x CD47 BEAT®
bispecific antibody
Multiple Myeloma;
AML planned in 2024
PHASE 1
ORPHAN DRUG
BCMA x CD38 x CD3
TREAT™ trispecific antibody
Multiple Myeloma
PHASE 1
ORPHAN DRUG
GRC 54276
Hematopoietic progenitor kinase 1 inhibitor
Solid Tumors
PHASE 1
PRODUCTS
COMPOUND
TARGET
CD38 x CD47 BEAT® bispecific antibody
INDICATION
Multiple Myeloma; AML planned in 2024
PHASE
STATUS :
PHASE 1 ORPHAN DRUG
PRODUCTS
COMPOUND
TARGET
BCMA x CD38 x CD3 TREATTM trispecific antibody
INDICATION
Multiple Myeloma
PHASE
STATUS :
PHASE 1 ORPHAN DRUG
PRODUCTS
COMPOUND
TARGET
Hematopoietic progenitor kinase 1 inhibitor
INDICATION
Solid Tumors
PHASE
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
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.
- Ichnos received authorizations from HREC in Australia and the U.S. FDA to initiate a Phase 1 first-in-human study of ISB 2001 for the treatment of MM and was granted ODD by the U.S. FDA for the same indication.
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-cell
- 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-cell. 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
Inflammation and Autoimmune Disease
The autoimmune disease assets have been out-licensed to enable greater focus on oncology.
For more details on our pipeline, please click here