Vir tempts Astellas

Sanofi had already looked foolish for selling dual-masked T-cell engagers to Vir for $100m, and now Vir has signed up Astellas as a partner for one of the assets, VIR-5500, in a deal worth $315m up front.

The announcement came as Vir reported updated phase 1 results with VIR-5500 that, although still only in a small number of patients, are an improvement over the promising data disclosed last year, which first raised questions about Sanofi’s decision to let the asset go. The results also look better than those seen with other prostate cancer hopefuls, on a cross-trial basis.

VIR-5500 is a PSMA-targeting T-cell engager that features masking of the tumour-associated antigen as well as its CD3-binding domain, which engages T cells. Vir believes this could improve the therapeutic index and lower toxicity.

Although the group still has a way to go to prove this, Astellas is clearly convinced. The Japanese company is shelling out $240m in cash and $75m in equity up front, plus agreeing to a $20m tech transfer milestone, expected by mid-2027; total milestones could reach $1.37bn.

Vir’s stock was up around 30% on Tuesday, with Evercore ISI’s Cory Kasimov describing the deal as a “smart move” that validates the potential of VIR-5500 as well as the group’s earlier pipeline.

The companies will share the costs of developing VIR-5500, with Astellas contributing 60% and Vir 40% globally; the smaller group has an option to co-promote the asset in the US, while Astellas will be solely responsible for commercialisation outside the US.

Sanofi isn’t losing out completely – Vir noted that, under the terms of the deal, it will share “a portion of certain collaboration proceeds” with the big pharma. However, the French group, which recently fired its chief executive officer, Paul Hudson, might be regretting selling VIR-5500, along with two other dual-masked T-cell engagers, for such a low price – especially as they came from its own $1bn purchase of Amunix.

Improving response rates

Last year, Vir reported data from its phase 1 trial of VIR-5500 in late-line metastatic castrate-resistant prostate cancer, showing a 58% PSA50 rate among 12 patients receiving a first dose of 120µg/kg or higher.

On Monday evening, it released updated results from the same study. While the group has now treated 58 patients, it focused on efficacy among 22 patients receiving at least 3,000µg/kg every three weeks where, the company said, it’s seeing the clearest clinical signals.

Among 17 prostate-specific antigen evaluable patients, 14 (82%) achieved PSA50. Vir noted during a conference call that, of the five non-evaluable patients, two were too early for analysis, while three discontinued therapy – something it said was typical in late-line prostate cancer trials, where patients tend to be very sick.

Evolving data with Vir’s VIR-5500 in late-line prostate cancer

Note: *there was also one unconfirmed PR; **across dose-escalation cohorts. Source: Company presentation.

On the face of it, this result looks better than other investigational assets in late-line prostate cancer, including two projects from Johnson & Johnson: the anti-KLK2 T-cell engager pasritamig, which produced a PSA50 rate of 42% among 33 patients receiving the go-forward regimen; and the androgen receptor-targeting HLD-0915, gained via the $3bn acquisition of Halda, which reported a 59% PSA50 rate among 22 patients completing at least two treatment cycles.

Janux’s PSMA-targeting masked T-cell engager JANX007, meanwhile, originally saw a 100% PSA50 rate in its phase 1 trial, Engager-PSMA-01, but in a heavily curated dataset of 16 pre-Pluvicto patients receiving target doses of 2-9mg. The latest Janux release saw this dwindle to 73% among 85 patients receiving 2mg or more. Notably, only that project's CD3-binding portion is masked.

JANX007 has also been linked with cytokine release syndrome, including 8% at grade 3 or higher. Vir boasted zero cases at grade 3 or higher among those receiving ≥3,000µg/kg – half of the patients had grade 1 CRS, and 9% at grade 2. However, there was one grade 3 CRS at a lower dose.

And there were also two events of treatment-related grade 3 and 4 blurred vision; the latter led to treatment discontinuation.

More data on VIR-5500 will be presented at the ASCO-GU meeting on Thursday, but Astellas is already claiming that the project could be a best-in-class T-cell engager for prostate cancer. The companies also have plans in taxane-naive CRPC, in combination with Xtandi, and hormone-sensitive prostate cancer.

While Vir claims to have found its go-forward dose, it wouldn’t give details on the call, and added that it’s still doing some dose optimisation work to satisfy FDA requirements. Pivotal trials are set to start next year.