Novartis calls time on TIM-3 and HIF2α
The company’s move could be a warning for rivals including GSK, AstraZeneca and Incyte.
The company’s move could be a warning for rivals including GSK, AstraZeneca and Incyte.
Novartis had been one of the leaders in the TIM-3 inhibitor race, but today it quietly slipped out the discontinuation of its project sabatolimab, following failure of the pivotal Stimulus-MDS2 trial in myelodysplastic syndrome.
The development could be bad news for the Swiss group’s TIM-3 rivals, which include GSK, Incyte, BeiGene and AstraZeneca. Meanwhile, Novartis has also canned a phase 1 asset, the HIF2α inhibitor DFF332.
TIM-3
All Novartis said today in its fourth-quarter results report was that Stimulus-MDS2, which tested sabatolimab plus azacitidine, had not met its primary endpoint. A spokesperson confirmed to ApexOnco that the entire programme had now been discontinued; sabatolimab was also being studied in acute myeloid leukaemia.
The most advanced TIM-3 contender now is GSK’s cobolimab, whose pivotal Costar Lung trial is set to yield data this year. While sabatolimab’s stumble could bode ill for this project, GSK is looking at a completely different setting and combination, with cobolimab being combined with the PD-1 inhibitor Jemperli and docetaxel.
Indeed, an analysis of OncologyPipeline shows that most TIM-3 assets are being developed in solid tumours alongside PD-(L)1 blockers. Astra’s sabestomig, meanwhile, is a PD-L1 x TIM-3 bispecific; however, previous efforts to combine these two mechanisms into one molecule, notably by Lilly and Roche, have fallen short.
Still, Novartis previously saw lacklustre phase 1 results with sabatolimab and the PD-1 inhibitor spartalizumab in solid tumours. It should soon become clear whether GSK can do any better with cobolimab.
TIM-3 inhibitors in clinical development
| Project | Company | Note |
|---|---|---|
| Sabatolimab | Novartis | Discontinued after failure of ph3 Stimulus MDS2 + azacitidine |
| Cobolimab | GSK | Ph3 Costar Lung + Jemperli + docetaxel; data due H2 2024 |
| Verzistobart | Incyte | Ph2 in Merkel cell carcinoma & H&N cancer + Zynyz + tuparstobart (anti-Lag3) |
| Surzebiclimab | BeiGene | Ph2 in H&N + tislelizumab |
| TQB2618 | Sino Biopharm | Ph2 China studies + PD-1 inhibitors in H&N and oesophageal cancers |
| Sabestomig | AstraZeneca | Ph1/2 in Hodgkin lymphoma & solid tumours |
| BC3402 | BioCity Biopharma | Ph1/2 China study + Imfinzi in liver cancer |
| LBL-003 | Nanjing Leads Biolabs | Ph1 China study in solid tumours |
| NB002 | Neologics Bioscience | Ph1 China study in solid tumours |
| Sym023 | Servier | Ph1 data presented at ESMO 2020; still listed in pipeline |
Note: all monoclonal antibodies except sabestomig, which is an anti-PD-L1 x TIM-3 bispecific. Source: OncologyPipeline.
Meanwhile, Novartis confirmed that it was no longer developing DFF332, a HIF2α inhibitor that had been in a phase 1 study in renal cancer but was missing from its updated pipeline today.
Merck & Co has an approved HIF2α inhibitor, Welireg; other companies looking at the same target include Arcus, NiKang Therapeutics, Betta Pharmaceuticals and Hansoh Pharma.
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