Vir shows up Sanofi

Masked T-cell engagers have become a big deal in recent months, and now dual-masked projects are on the agenda, thanks to Vir Biotechnology. The company just presented intriguing early data from two projects it licensed from Sanofi in August, and was rewarded by a 58% boost in its share price on Wednesday.

Vir paid just $100m up front for three dual-masked T-cell engagers, so looks to have bagged a bargain. Meanwhile Sanofi, which has made several oncology missteps but is still interested in the space, might now look foolish for letting these assets go – especially as they came from its own $1bn purchase of Amunix.

Vir reported data on VIR-5818 (previously SAR446309), which targets HER2, and VIR-5500 (previously SAR446329), which hits PSMA.

Conditionally active T-cell engagers, such as Janux’s rival PSMA-targeting JANX007, have already seen success, but only that project's CD3-binding portion, which engages T cells, is masked. Vir’s assets, meanwhile, feature masking of the tumour-associated antigen as well as CD3-binding domains, something the company says could improve the therapeutic index and lower toxicity.

This remains to be proven definitively, but investors clearly believe that the company is off to a good start.

PSMA

The data on VIR-5500 come from a phase 1 trial in heavily pretreated metastatic castration-resistant prostate cancer.

The 58% PSA50 rate, albeit among just 12 patients receiving 120µg/kg or higher, looks competitive with many of the current crop of prostate cancer hopefuls – with the exception of Janux’s JANX007, which recently saw 100% of patients achieve PSA50.

However, Janux’s dataset is heavily curated, including only post-Pluvicto patients treated with doses of 2mg or higher; the VIR-5500 data appear impressive given that this project is still early in dose escalation.

And there was only a 25% rate of CRS with VIR-5500 – none at grade 3. Meanwhile, 100% of patients receiving JANX007 had CRS, 6% at grade 3. Janux’s stock dipped 6% on Wednesday.

Vir reckons it has plenty of headroom to increase the dose of VIR-5500. The company declined to say when it planned its next data update. 

HER2

The VIR-5818 results came from a phase 1 trial in various heavily pretreated HER2-expressing cancers, including breast and colorectal.

Among 20 subjects receiving 400µg/kg or higher there were four responses; this includes unconfirmed responses, although Vir didn’t specify how many. 

Instead, Vir zoomed in on six microsatellite-stable colorectal cancer patients receiving 400µg/kg or more, where there were two confirmed partial responses. During a conference call, Vir’s head of oncology, Mika Derynck, added that there could be potential for an accelerated regulatory pathway here, given the unmet need.

However, Enhertu has shown an ORR of 47% in late-line HER2-positive colorectal cancer in the Destiny-CRC02 trial.

As for safety, there was a relatively low 16% rate of grade 3 or higher treatment-related adverse events, and no grade 3 or higher CRS. There were two cases of grade 3 pneumonitis, however. Dose escalation continues, and Vir is now focused on dosing every three weeks.

The group also picked up another dual masked T-cell engager from Sanofi, the EGFR-targeting VIR-5525, and phase 1 is set to start this half. Vir also hopes to expand into new targets. After being better known for infectious diseases, the group might have become a cancer name to watch, although it still has much to prove.

This story has been updated to include the financial terms of the deal with Sanofi.