ESMO 2024 preview – conjugates in the spotlight

Release of the titles for many of the presentations accepted for this year’s ESMO has given investors the first glimpse of what to expect at the conference that now rivals ASCO as the world's most important oncology meeting.

True, the most eagerly awaited sessions remain under wraps, so nothing is known yet about any of ESMO’s late-breakers, of which there are many, or about the prestigious presentations selected for any of the three presidential slots. But several regular abstracts on antibody-drug conjugates are bound to turn heads, not least because they might indicate the success of recent deal activity.

For instance, SystImmune, the US subsidiary of Biokin/Baili, last December licensed the anti-EGFR x HER3 ADC izalontamab brengitecan to Bristol Myers Squibb for $800m up front. Izalonta-B’s urothelial carcinoma trial features in an oral presentation on ESMO’s opening day. Toxicity will be top of investors' minds given the partial US clinical hold for MediLink and BioNTech's HER3 ADC YL202/BNT326. 

In April Genmab paid $1.8bn for ProfoundBio, largely on the strength of the private biotech’s rinatabart sesutecan, an ADC against folate receptor alpha (FRα). Rinata-S has secured a mini oral presentation covering its endometrial cancer study.

And the antigens B7-H3 and B7-H4 have been in focus thanks to GSK’s double dip, where in two separate transactions last year the UK group licensed Hansoh Pharma’s HS-20093 and HS-20089 respectively, not to mention Merck & Co’s monster tie-up with Daiichi Sankyo, which included the anti-B7-H3 ADC ifinatamab deruxtecan.

ESMO will feature both approaches; MediLink’s YL201 could be of interest given the aforementioned clinical hold for YL202, while AstraZeneca’s puxitatug samrotecan will cause intrigue given that its sole phase 1 trial started back in October 2021, despite which it hasn't yet yielded any clinical data.

Selected ESMO 2024 oral presentations featuring ADCs

Source: ESMO.

That said, perhaps the greatest intrigue among the ADCs known to feature at ESMO so far surrounds Pfizer’s Seagen-derived PF-08046054, an anti-PD-L1 ADC that was highlighted at Pfizer’s R&D day in February.

This scientific approach features just two other named molecules, according to OncologyPipeline: Shanghai Henlius/MediLink’s HLX43/YL222 and Pfizer’s PF-08046037 (while PF-08046054 has an auristatin E payload, PF-08046037 uses a TLR7 agonist). Early data have shown an ORR of 21% (50% including unconfirmed responses) among PD-L1-positive head and neck cancer patients given PF-08046054 at ≥1.25mg/kg.

ADC targets that already face extensive competition include TROP2 and Claudin18.2, and ESMO will feature at least two of each, with oral presentations on projects in development by Escugen Biotechnology and Jiangsu Hengrui.

And in Claudin6 Daiichi Sankyo has a presentation on DS-9606a, an ADC notable for not being partnered with either AstraZeneca or Merck. In the same space the spotlight will fall on Torl’s TORL-1-23.

That last ADC has been prominent given the speed with which the privately held Torl has been moving it through development – an effort that could seen see it overtake BioNTech’s Car-T project BNT211, which was once the sector’s furthest-advanced anti-Claudin6 asset.

ESMO will take place in Barcelona, Spain, on 13-17 September 2024. This is a corrected version of a story published earlier.