Like MacroGenics, Sanofi tries to square an uneasy circle

Sanofi’s remaining CEACAM5-targeting antibody-drug conjugate bears a key resemblance to the ADC it discontinued two years ago, it's been revealed in the latest published list of international non-proprietary names (INNs).

The 134th iteration of the proposed INNs from the World Health Organization discloses that both projects use the same antibody, namely tusamitamab. Those following the burgeoning field of ADCs will note that an identical revelation emerged last year regarding MacroGenics’ new anti-B7-H3 ADC; similarly, AbbVie is putting its faith in cMet in a follow-on ADC that uses the same MAb as its marketed drug Emrelis.

Of course, the fate of a follow-on ADC need not necessarily be tied to that of a first attempt that used the same MAb, given that in all three cases a different payload is utilised. And all three companies have made the switch to a topoisomerase 1 inhibitor payload, in preference to a less popular modality.

For Sanofi, its first anti-CEACAM5 ADC, derived from a deal with ImmunoGen and called tusamitamab ravtansine, was discontinued in December 2023 after failing the Carmen-LC03 trial in second-line non-squamous NSCLC.

But Sanofi declared its continued faith in CEACAM5, which it was separately targeting with a Pfizer-partnered, Seagen-derived ADC then coded SGN-CEACAM5C. The latter now carries the INN tusamitamab sonditecan. 

Tmalin and more

The latest INNs also concern Mythic’s ill-fated anti-cMet ADC, now called zevontabart vedotin, for which there still remains some hope of development in the hands of a new licensee.

Two assets that use MediLink’s high-profile Tmalin linker-payload technology, Zai Lab’s zocilurtatug pelitecan and BioNTech’s beruzatatug pelitecan, also feature, as does Corbus’s lead pipeline project, the CSPC Pharmaceuticals-derived anti-Nectin-4 ADC now called sutantatug envedotin, and one of Merck KGaA’s first forays into ADC development.

Chia Tai, which has a growing presence in conjugates, is also notable by virtue of having the first INN proposed for one of its ADCs, a biparatopic HER2-targeting molecule now revealed to carry a warhead called deuderuxtecan. That warhead appears to be a deuterated form of Daiichi Sankyo’s DXd, but how Chia Tai obtained rights to it is unclear.

The list also throws up a curiosity in the shape of the TA-MUC1-targeting compound formerly known as DS-3939. This is based on the antibody gatipotuzumab, which Daiichi Sankyo acquired a year ago for $133m from Glycotope, but its INN reveals that the MAb it actually uses isn’t gatipotuzumab but sacomitatug; the latter is an analogue of the former, an AACR publication disclosed last month.

ADCs with recently proposed INNs

Source: WHO & OncologyPipeline.