Cytospire’s backers buy in as Pfizer exits
No sooner does one gammadelta-focused biotech die than another takes its place.
No sooner does one gammadelta-focused biotech die than another takes its place.
There’s a remarkable similarity between Cytospire Therapeutics, a private UK biotech that just closed an $81m series A venture financing round, and Pfizer: both have worked on gammadelta T-cell engagers, and their lead projects in this field, CYT X300 and PF-08046052 respectively, both target EGFR.
Unfortunately for Cytospire, on the same day that this company talked up the prospects of the still preclinical CYT X300, which is the key asset underpinning its $81m raise, Pfizer disclosed the discontinuation of PF-08046052. The latter move came amid generally waning enthusiasm in γδ T cells, which earlier saw the winding up of Lava Therapeutics, PF-08046052’s originator.
Lava was the most notable player to go all-in on the prospects of using γδ T cells as a vehicle for immune system engagement, closing a $100m IPO in 2021. Its work centred on using a high-affinity Vδ2 binder to engage these cells, which represent around 5% of the total T-cell population, and are thought to have certain advantages over typical αβ T cells.
Two big players, Johnson & Johnson and Seagen, saw enough to endorse this work through licensing deals, with the latter passing to Pfizer when that group acquired Seagen. However, Lava failed to attract additional funding, and first cut costs and then was acquired by the royalty financing specialist Xoma (itself recently sold to another royalty aggregator, Ligand).
One basis for Lava’s distressed sale was the potential of proceeds from milestones relating to JNJ-89853413, the asset licensed to J&J, and PF-08046052. The latter’s discontinuation effectively extinguishes any hope Ligand might have of a return on it, barring the unlikely possibility of Pfizer selling PF-08046052 on to yet another entity.
The Cytospire difference
Like PF-08046052, Cytospire’s CYT X300 targets EGFR, and is a γδ T-cell engager. However, CYT X300 has an important difference versus the Lava/Pfizer project, as disclosed in a poster at AACR in 2025.
“CYT X300 incorporates a novel binder to an epitope present on all γδ T cells including tissue/tumour resident Vδ1 and Vδ3 cells,” the poster revealed, claiming that this caused activation of all γδ T-cell subsets. In contrast, the Vδ2 binder used in PF-08046052 limited that project to the engagement of a blood-resident subset of γδ T cells.
Of course, whether this makes a difference won’t become apparent until CYT X300 enters clinical trials, which Cytospire says are planned in EGFR-positive solid tumours, such as colorectal, head and neck and non-small cell lung cancers. For its part Pfizer doesn’t appear ever to have published human data on PF-08046052.
Similar but different
| Project | Company | Mechanism | Engager target | Status |
|---|---|---|---|---|
| PF-08046052 | Pfizer (ex Seagen, ex Lava) | EGFR γδ T-cell engager | Vδ2 | Discontinued in ph1 solid tumour study |
| CYT X300 | Cytospire Therapeutics | EGFR γδ T-cell engager | Undisclosed, includes Vδ1 & Vδ3 epitopes | Preclinical; clinical study in EGFR+ve solid tumours planned |
Source: OncologyPipeline.
PF-08046052’s discontinuation was disclosed at Pfizer’s first-quarter update on Tuesday, alongside those of two other cancer-focused new molecular entities.
One was PF-08046037, an anti-PD-L1 ADC that used a TLR7 agonist as its payload. ApexOnco reported the discontinuation of PF-08046037 in January, but Tuesday was the first formal admission by Pfizer that the molecule had been dropped from its pipeline.
The other was the CD47-SIRPα fusion protein maplirpacept, the final remaining asset from Pfizer’s $2.3bn acquisition of the CD47-focused company Trillium back in 2021. The company earlier scrapped three maplirpacept trials, so termination of the remaining two, Maptivate-6 and Magnetismm-20, doesn’t come as a great surprise.
Maptivate-6 once aimed to enrol 70 patients but recruited just 30, while Magnetismm-20 stopped enrolment at 59 of a planned 90; one of the earlier maplirpacept studies was ended owing to the inability to recruit patients.
Coincidentally, Trillium had once worked on an anti-EGFR T-cell engager, TTI-2341, but that didn’t focus on γδ T cells, and was dropped before the takeover by Pfizer.
Link to OncologyPipeline project
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