ESMO 2024 movers – VEGF bispecifics win, TIGIT loses

With the curtains coming down on ESMO this year’s instalment has lent further support to the latest big drug development theme: bispecific antibodies against VEGF x PD-(L)1. These are set to be a key modality to watch, now having yielded data in settings beyond lung cancer, and driving up the share prices of Akeso, Summit, BioNTech and Instil Bio.

Ironically, that last name didn’t even have a presence at ESMO, but its climb – 27% over the ESMO weekend, and 390% since the titles went live in July – was down to it riding on the coattails of Akeso/Summit’s ivonescimab. With degraders in focus Prelude led the biotech fallers, but ESMO 2024 might be better remembered for the latest collapse of investor sentiment around TIGIT.

Overall, the conference was seen by many as lacking the “wow” factor of previous years, and many key presentations concerned multi-year follow-up data from approved uses of checkpoint inhibitors. A sign of the apparent effort to fill available space was Amgen’s AMG 193, promoted to the presidential session with data that ultimately disappointed.

This analysis chiefly concerns share price movements between 12 September, the day before the meeting opened, and 16 September, its last day of formal presentations.

ESMO 2024 risers

Note: *16 Sep close vs 12 Sep close.

Enthusiasm around Akeso/Summit’s ivonescimab exploded around the World Lung conference, and this momentum continued at ESMO, which took place a week later and included data in settings including triple-negative breast and colorectal cancers.

Data in the latter, from a Chinese trial, produced an astonishing 88% ORR in a first-line study in combination with the anti-CD47 MAb ligufalimab and chemo. BioNTech's own PD-L1 x VEGF contender BNT327 also featured at ESMO, alongside that company's anti-CTLA-4, Claudin6 and other projects.

In post-EGFR TKI EGFR mutant NSCLC, the uncontrolled portion of a phase 2/3 Chinese trial produced a confirmed response rate of 59% for BNT327 plus chemo, numerically better than the 51% ivonescimab showed in its analogous Harmoni-A trial. These data, along with those in TNBC and growing excitement around this mechanism, contributed to BioNTech's 18% climb.

It’s also impossible to ignore the climb of Nuvalent on data with its highly targeted AKL and ROS1 inhibitors, and the group has already capitalised on ESMO by raising $500m in a secondary offering. The question for investors is whether the highly impressive results can sustain Nuvalent’s $6.8bn market cap.

Degrader enthusiasm waxed and waned, as shown by C4 Therapeutics stock’s fluctuation on CFT1946 data, but Astellas’s KRAS G12D degrader clearly disappointed – providing a possible boost to Revolution, a key player in pan-KRAS inhibition. 

Among big pharma datasets, ESMO saw 10-year follow-up data from the Checkmate-067 and Keynote-006 trials, which back first-line melanoma approvals of Opdivo (2016) and Keytruda (2015) respectively. Keynote-522, in perioperative triple-negative breast cancer (2021 approval), saw Keytruda plus chemo cut risk of death by 34% versus chemo.

ESMO 2024 fallers

Note: *16 Sep close vs 12 Sep close.

As for degraders, if Bristol’s BMS-986365 was the one clearly positive outlier, the ESMO wooden spoon went to the selective SMARCA2 degrader PRT3789, whose limited activity caused Prelude to fall 46% over the ESMO weekend.

That might have led the ESMO fallers, but an arguably greater disappointment came from iTeos/GSK’s anti-TIGIT MAb belrestotug; while inclusion of the Galaxies Lung-201 study as an ESMO late-breaker brought hope, ultimately toxicity and the precedent of Roche’s tiragolumab snuffed this out.

Sutro was down as its FRα-targeting ADC luveltamab tazevibulin was eclipsed by data on Genmab’s rival asset rinatabart sesutecan, gained via this year’s purchase of ProfoundBio. Rina-S showed an ORR of 50% at the go-forward dose, 120mg/m² once every 3 weeks, in patients with heavily pretreated ovarian cancer; crucially, responses were seen regardless of FRα levels.

An update on Bicycle Therapeutics’ Nectin-4-targeting toxin conjugate zelenectide pevedotin showed a 45% ORR in 38 bladder cancer patients, but there are fears about how the asset, which went into phase 3 this year, will compete against Astellas/Pfizer’s Padcev. 

And MacroGenics has now seen eight treatment-related deaths in the Tamarack study of its anti-B7-H3 ADC vobramitamab duocarmazine, up from five at the last count; the project’s future looks bleak after a recent halt in dosing.

All of ApexOnco’s coverage of ESMO 2024 is available on free download.