Merck & Co gets in on the bispecific act

Given how hot anti-VEGF x PD-(L)1 bispecifics have become it was only a matter of time before the industry's biggest hitters got in on the act. Today Merck & Co became the first big pharma group to stake a claim, shelling out $588m up front for LaNova Medicines' LM-299, an anti-VEGF x PD-1 MAb that only entered the clinic last month.

This might make the fee look rich, but Summit paid Akeso $500m for ivonescimab, and just this week BioNTech bought out Biotheus, originator of the competing BNT327, for $800m. Undoubtedly the prices of similar assets will now rise, but it's also important to remember that Merck has its Keytruda franchise to protect, so was especially motivated to do a deal.

Indeed, the company's mind might have been focused by Akeso's Harmoni-2 data presented at September's World Lung conference, showing – with caveats – ivonescimab beating Keytruda head to head in PD-L1-expressing first-line lung cancer. Ivonescimab, picked up by Summit for $500m up front in December 2022, marked the start of the VEGF x PD-(L)1 bispecific craze.

Asset prices

Still, it's taken a while for other assets' prices to reach ivonescimab's; a year ago BioNTech secured ex-China rights to Biotheus's BNT327 for $55m, and as recently as August this year the distressed TIL player Instil Bio was able to effect a strategic pivot into this space when it spent just $50m in "up-front and potential near-term payments" for rights to ImmuneOnco's IMM2510/SYN-2510.

During its third-quarter earnings call last month Merck said it was keeping an eye on the VEGF x PD-(L)1 space, and "watching carefully the ability to turn PFS into OS". That was a reference to ivonescimab's Harmoni-2 trial, whose win was on PFS, with nothing said yet about the all-important OS result.

It's interesting to note that Merck has put its money on combining VEGF with PD-1 and not with PD-L1. The former is ivonescimab's mechanism, while the latter that of BNT327, and BioNTech has argued that engaging PD-L1, a protein expressed on cancer cells, allows precise VEGF blockade by anchoring the antibody to the tumour.

It also won't go unnoticed that all of the licensing deals in this space have so far concerned projects originated in China; all other anti-VEGF x PD-(L)1 bispecifics in clinical trials at present appear to be at Chinese companies, and most of these will likely have an eye on licensing.

When LaNova revealed the start of its phase 1 study of LM-299 it made a point of stating on its website that global rights to the molecule were “available".

With Merck now throwing its hat into the ring, investors can rest assured that the business development teams of Bristol Myers Squibb, Roche, AstraZeneca and others are seeking out their next move. And the likes of 3SBio, Sinocelltech, OncoC4, Ottimo Pharma and Crescent Biopharma will be freshening up their pitch decks.

Recent activity in the VEGF x PD-(L)1 space

Source: OncologyPipeline.