Gilead deals more checkpoint disappointment
Gilead might be known for splashing the M&A cash, but it has found a target that apparently doesn’t warrant further investment: HLA-G. TTX-080, originated by Tizona Therapeutics, was missing from Gilead’s fourth-quarter pipeline update yesterday, followed by reports that the biotech had ditched its smaller partner. In 2020, Gilead spent $300m on a 49.9% stake in Tizona, with an option to acquire the company in full for another $1.25bn. Progress with the asset has been unclear, with the most recent release on Tizona's website dated October 2021; Tizona told ApexOnco that it was now looking for a new partner. HLA-G is said to be an immune checkpoint expressed in multiple tumour types, and Gilead had hoped to hit tumours unresponsive to PD-(L) inhibitors. But other groups have already thrown in the towel, including Roche and Johnson & Johnson, and only a couple of clinical-stage contenders remain. Gilead also yesterday disclosed the discontinuation of a second-generation Arcus-partnered Tigit inhibitor, the Fc-enabled AB308. And if hope still remained for the CD47 inhibitor magrolimab this was further extinguished today with news of an increased risk of death with the project in the Enhance-3 AML study; magrolimab work in haematology has been discontinued.
The HLA-G pipeline
| Project | Company | Modality | Status |
|---|---|---|---|
| IVS-3001 | Invectys | Autologous HLA-G Car-T | Ph1/2 in solid tumours completes Jun 2026* |
| CAR001 | Ever Supreme Bio Technology | Allogeneic HLA-G Car γδ T cells | Ph1/2 in solid tumours to start Apr 2024 |
| TTX-080 | Tizona Therapeutics/ Gilead | Anti-HLA-G MAb | Ph1 in solid tumours; project missing from Gilead’s Q4 2023 pipeline update |
| RO7515629 | Roche | Anti-HLA-G T-cell engager | Discontinued at ph1 Feb 2024 |
| JNJ-78306358 | Johnson & Johnson | Anti-HLA-G T-cell engager | Discontinued at ph1 Jan 2023 |
| NKILT-CIR-NK | NKILT Therapeutics | HLA-G-targeting CIR-NK cells | Preclinical data at SITC & ASH 2023 |
| AR087 | Y Biologics | Anti-HLA-G MAb | Preclinical |
| DSP216 | Kahr Medical | Anti-HLA-G/CD47 fusion protein | Preclinical |
| IVS-4001 | Invectys | Anti-HLA-G MAb | Preclinical |
| UCB4594 | UCB Pharma | Anti-HLA-G MAb | Preclinical |
*Investigator-sponsored trial. Source: OncologyPipeline.
After this article was first published Tizona clarified that it was completing a phase 1b trial of TTX-080, and seeking a new partner for this project.
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