Early-stage changes at Roche
Among the various early-stage pipeline changes Roche disclosed in its full-year earnings update on Thursday, several should pique the interest of oncology investors. One is the discontinuation of a Chugai-originated anti-GPC3 T-cell engager, ERY974, at the same time as the development of codrituzumab, a naked anti-GPC3 MAb developed by the Genentech division, is apparently ongoing. GPC3 emerged as a high-profile solid tumour target for Car-T therapy courtesy of AbelZeta/AstraZeneca data at last year's ASCO, though other modalities have yet to impress, and codrituzumab itself failed a phase 2 liver cancer study in 2016. Also notable is the discontinuation of RG7827, which appears to be the fourth FAP-targeting molecule to have been ditched by the Swiss group in recent years, after RG6189, simlukafusp alfa and RG7386. Meanwhile, new entries into Roche's phase 1 pipeline include the anti-DLL3 ADC RG6810, which is presumably Roche's code for Innovent's IBI3009, the subject of a recent deal, and RG6620, a KRAS G12D inhibitor to complement Roche's G12C-specific divarasib. Last October ApexOnco reported that the KRAS G12D inhibitor GDC-7035 was starting phase 1, and this can be assumed to be the molecule now coded RG6620.
Selected pipeline changes at Roche
| Project | Mechanism | Clinical status | Note |
|---|---|---|---|
| What’s in? | |||
| P-MUC1C-ALLO1 | TA-MUC1 Car-T | Ph1 in solid tumours | Via $1bn Poseida acquisition in Nov 2024; Daiichi has an anti-TA-MUC1 ADC, DS-3939 |
| RG6810/ IBI3009 | DLL3 ADC | Ph1 in SCLC & NETs | Licensed from Innovent for $80m in Jan 2025 |
| RG6620/ GDC-7035 | KRAS G12D inhibitor | Ph1 in KRAS G12Dm solid tumours | Ph1 start reported in Oct 2024 |
| RG6561 | Undisclosed | Ph1 in solid tumours | Might be RO7759065, which started ph1 last year |
| What’s out? | |||
| RG7827/ RO7122290 | FAP x 4-1BB fusion protein | Ph1/2 in MSS colorectal cancer, + anti-CEA T-cell engager cibisatamab | Fourth discontinuation of a Roche FAP-targeting asset |
| Runimotamab (RG6194) | HER2 T-cell engager | Ph1 in HER2-expressing cancers | – |
| Efbalropendekin alfa (RG6323/ RO7310729/ XmAb24306) | Fc-fusion IL15/IL15Rα protein | Ph1 in multiple myeloma | Was also studied in solid tumours |
| ERY974 | GPC3 T-cell engager | Ph1 in liver cancer | Codrituzumab, a naked MAb against GPC3, remains in Roche pipeline despite failing in ph2 |
| SPYK04 | RAF-MEK molecular glue | Ph1 in solid tumours | Discontinuation disclosed by Chugai Oct 2024 |
Source: Q4 2024 earnings report.
1006
