Bristol changes tack in Claudin18.2

Bristol Myers Squibb terminated its deal with LaNova Medicines covering the Claudin18.2-targeting ADC LM-302/TPX-4589, ApexOnco has learned. The project, which Bristol had inherited through its $4.1bn takeover of Turning Point Therapeutics in 2022, entered phase 3 in gastric cancer this year.

Ironically, on the same day Bristol confirmed its exit the FDA approved its first ever anti-Claudin18.2 drug, namely Astellas’s Vyloy. It’s possible that Bristol isn’t entirely abandoning the highly competitive space of Claudin18.2 blockade, having four months ago agreed to supply Opdivo into a combo study of givastomig, I-Mab’s anti-Claudin18.2 x 4-1BB bispecific. 

Still, the latter deal is merely a clinical trial collaboration, at this stage signifying no financial commitment beyond the provision of Bristol’s anti-PD-1 MAb. The phase 1 study is evaluating givastomig monotherapy in all-comer solid tumours, or an Opdivo plus chemo combo in Claudin18.2-positive gastric/oesophageal cancers.

Givastomig was originated by I-Mab and ABL Bio, and it must be noted that bispecific MAbs using 4-1BB co-stimulation haven’t fared especially well across the industry.

Too competitive?

As such, it’s possible that Bristol wants no active involvement in givastomig, and simply decided that Claudin18.2 was too competitive a space to enter without a potentially best-in-class molecule.

Such a view wouldn’t instil confidence in LaNova’s LM-302, an ADC using an auristatin payload and cathepsin-cleavable linker that until now was seen as one of the important assets that Turning Point brought to Bristol, after the now marketed Augtyro. Turning Point licensed it from LaNova for $25m up front in May 2022, at which point it was in phase 1.

Because the up-front fee was so low it’s likely that LM-302 (later coded TPX-4589 and BMS-986476) carried a relatively insignificant valuation on Bristol’s balance sheet once Turning Point was acquired just a month later, explaining why Bristol never formally announced the deal’s termination.

Recently LaNova’s R&D pipeline began listing LM-302 as the company’s lead project, whose global licensing rights were shown as “available”. On Friday a Bristol spokesperson confirmed to ApexOnco that the company “did terminate its agreement with LaNova last year”.

Astellas

Such shifts behind the scenes are probably positive for Astellas’s zolbetuximab, which as of Friday is US-approved as Vyloy for first-line, Claudin18.2-positive, HER2-negative gastric/GEJ adenocarcinoma, as part of a chemo combo.

Unlike LM-302 and givastomig Vyloy is a naked MAb, and any setbacks among Claudin18.2 competitors give the Astellas drug a better shot to capitalise on its first-to-market status, especially given the questions about its supporting Spotlight and Glow studies. US approval came 10 months after a complete response letter that cited manufacturing deficiencies.

Notable competing anti-Claudin18.2 ADCs include AstraZeneca’s Keymed-originated AZD0901, but Merck & Co recently handed rights to MK-1200 back to Kelun. Over the past year biotech investors had bid up shares in Elevation Oncology on the back of its ADC, EO-3021, but the stock collapsed in August when US data failed to live up to the promise of an earlier Chinese trial.

This story has been updated.