Project Details
Project Description
We are developing a new immuno-oncology biologic treatment based on a novel series of flexible CTLA4-Ig fusion proteins (FlexCTLA4-Ig) that activate the immune system and trigger antitumour immunity in mouse models. Our FlexCTLA4-Ig series has an immunostimulatory mechanism of action distinct to current cancer immunotherapies, with potential utility in oncology and infectious diseases. A provisional patent application covering FlexCTLA4-Ig compositions and their uses has been filed, and we are currently revising a manuscript describing the anti-tumour effects of FlexCTLA4-Ig for second round review at the leading journal Nature.
FlexCTLA4-Ig fusion proteins were developed by Ross Dickins (Monas University) in collaboration with Nadia Kershaw (WEHI) based on extensive in-house biophysical data. Compositionally they are similar to CTLA4-Ig (abatacept), a US >$3B pa immunosuppressive biologic marketed by BMS mainly for rheumatoid arthritis. However, remarkably, by simply introducing flexibility into CTLA4-Ig we have converted it from an immunosuppressor to an immunostimulator with potent anti-tumour activity. Unlike existing cancer immunotherapies,
FlexCTLA4-Ig activates anti-tumour immunity through specific targeting of antigen-presenting cells. FlexCTLA4-Ig simultaneously perturbs the CTLA4 and PD(L)1 checkpoints, both critical targets in immuno-oncology.
Product development of FlexCTLA4-Ig for cancer and infectious disease is significantly de-risked with respect to manufacturing, safety, and likely similar PK/PD profile based on compositional similarity to CTLA4-Ig/abatacept (despite opposite functionality). Importantly our current mouse data do not raise any safety concerns. Based in its unique mechanism of action we anticipate FlexCTLA4-Ig may have efficacy in cancers resistant to existing cancer immunotherapies, or as combination therapies.
FlexCTLA4-Ig fusion proteins were developed by Ross Dickins (Monas University) in collaboration with Nadia Kershaw (WEHI) based on extensive in-house biophysical data. Compositionally they are similar to CTLA4-Ig (abatacept), a US >$3B pa immunosuppressive biologic marketed by BMS mainly for rheumatoid arthritis. However, remarkably, by simply introducing flexibility into CTLA4-Ig we have converted it from an immunosuppressor to an immunostimulator with potent anti-tumour activity. Unlike existing cancer immunotherapies,
FlexCTLA4-Ig activates anti-tumour immunity through specific targeting of antigen-presenting cells. FlexCTLA4-Ig simultaneously perturbs the CTLA4 and PD(L)1 checkpoints, both critical targets in immuno-oncology.
Product development of FlexCTLA4-Ig for cancer and infectious disease is significantly de-risked with respect to manufacturing, safety, and likely similar PK/PD profile based on compositional similarity to CTLA4-Ig/abatacept (despite opposite functionality). Importantly our current mouse data do not raise any safety concerns. Based in its unique mechanism of action we anticipate FlexCTLA4-Ig may have efficacy in cancers resistant to existing cancer immunotherapies, or as combination therapies.
| Status | Finished |
|---|---|
| Effective start/end date | 31/07/22 → 30/11/24 |