Another vote of no-confidence in co-stimulated bispecifics
BioNTech and Genmab's acasunlimab is the latest 4-1BB project to stumble.
BioNTech and Genmab's acasunlimab is the latest 4-1BB project to stumble.
BioNTech’s decision to walk away from the Genmab-partnered acasunlimab adds further doubt over whether adding co-stimulation to an antigen-targeting domain can yield an antibody with acceptable safety and efficacy.
Acasunlimab’s mechanism involves bispecific targeting of PD-L1 and 4-1BB, and the molecule is a result of the tie-up the two companies struck back in 2015. The surprising thing about BioNTech’s decision (formally down to “portfolio strategy”) is that BioNTech was playing up acasunlimab as recently as two months ago, telling ApexOnco about the difficult work it had done to strike the balance needed in such a conditionally acting bispecific.
The project yielded promising OS data at ASCO, but perhaps its liver toxicity signal proved too much for BioNTech. The German company’s move follows Inhibrx’s discontinuation in February of the similarly acting INBRX-105, and a focus will now fall on MCLA-145, which Merus is evaluating in a Keytruda combo study.
Clinical-stage anti-PD-(L)1 x 4-1BB bispecific MAbs
| Project | Company | Status |
|---|---|---|
| Acasunlimab | Genmab | Starts ph3 in 2024; BioNTech handed back rights Aug 2024 (“portfolio strategy”) |
| LBL-024 | Nanjing Leads Biolabs | Permitted to begin single-arm pivotal trial geared towards China approval |
| QLF31907 | Qilu Pharmaceutical | China ph2 in melanoma & urothelial carcinoma |
| S095012/ PRS-344 | Servier | Ph1/2 in solid tumours |
| AP203 | AP Biosciences | Ph1/2 Apt-Cube trial |
| PM1003 | Biotheus | Ph1/2 |
| ATG-101/ YN-051 | Antengene Corporation | Ph1 data in Nov 2023 |
| Ragistomig (ABL503) | ABL Bio/ I-Mab | Ph1 data at ASCO 2024 |
| MCLA-145 | Merus | Ph1 Keytruda combo |
| BH3120 | Hanmi Pharmaceutical | Ph1 started Dec 2023 |
| IBI319* | Innovent/ Lilly | Ph1, but no longer listed in Lilly pipeline |
| FS222 | InvoX Pharma | Ph1 |
| INBRX-105 | Inhibrx Biosciences | Terminated in ph2, Feb 2024 |
| NM21-1480 | Numab Therapeutics | Terminated in ph1/2, Feb 2024 (“business decision”) |
Note: *hits PD-1; the rest all hit PD-L1. Source: OncologyPipeline.
That’s not to say that this is the end of acasunlimab: the project is still scheduled to enter phase 3 in NSCLC this year, but this effort will now be down to Genmab alone.
More co-stimulation candidates
And Genmab/BioNTech’s work on other joint assets continues, including two more that aim to stimulate 4-1BB: BNT312 (GEN1042), which additionally targets CD40; and BNT314 (GEN1059), which also hits EpCAM.
BNT312 in particular seems on thin ice, with Genmab admitting during last year’s Jefferies London healthcare conference that more dose escalation work was needed; the companies have previously said that phase 1/2 data are due this half and that next steps are will be determined in 2024.
In addition, the partners are developing another bispecific antibody, BNT322 (GEN1056), against undisclosed targets, and an anti-OX40 antibody hexamer known as BNT315 (GEN1055).
All of these projects appeared in BioNTech’s second-quarter results presentation, but none was mentioned specifically during the group’s conference call yesterday, with the focus largely on the PD-L1 x VEGF bispecific BNT327.
Genmab will present its second-quarter results on Thursday, so clues could emerge then about the status of these other assets.
This is an updated version of a previously published story.
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