ESMO 2025 movers – FDA volte-face to the rescue

If things looked hopeless for IO Biotech going into ESMO then the company emerged from the conference as the surprise winner. This wasn’t to do with data presented at the conference, however, but rather with what investors perceived as a change of heart at the FDA, which if true could allow IO’s lead project, Cylembio, to be filed for approval after all.

Though Summit Therapeutics is now going to chance its hand with the FDA too, there was no redemption for this company, which fell, as did Perceptive Therapeutics, ESMO’s biggest loser. Perhaps the most negative turn of sentiment, meanwhile, concerned Genmab, hit at ESMO with a double whammy of new competitors in the anti-folate receptor alpha ADC arena, and in colorectal cancer.

This analysis concerns share prices at close on 21 October, ESMO’s last day, versus 10 October, the last trading day before all abstracts except late-breakers went live. There were a few other significant moves, including over the ESMO weekend itself, but comparing against 10 October appears to be the best way to capture the key ESMO movements.

Roundabout surprise

It was via a roundabout route that IO Biotech surprised positively, courtesy of another biotech, Replimune, which revealed that the FDA had after all accepted its resubmission for the oncolytic virus therapy vusolimogene oderparepvec.

Before that vuso-vec had been slammed with a CRL, as well as at a subsequent meeting at which the FDA advised against its resubmission. IO Biotech finds itself in a somewhat similar situation with its immunotherapy Cylembio, which narrowly missed in its Keynote-D18 trial, and over which the FDA had told the group not to file.

While Keynote-D18 was presented at ESMO, it was renewed hope that the FDA might be changing its stance that enabled IO stock to surge 85% over the period in question. The group had gone into ESMO with its stock off 65% compared with the day before the FDA’s knockback, and the shares are still down some 35% compared with then, indicating that IO isn’t yet out of the woods.

Other ESMO risers included Celcuity, whose 42% climb on the promise of gedatolisib was perhaps the biggest rise that can be attributed directly to ESMO data. Meanwhile, Arcus and Gilead kept the TIGIT dream alive with domvanalimab, despite the clear failure of Roche’s toragolumab in four key studies presented at ESMO.

Selected ESMO 2025 risers

Note: *21 Oct 2025 close vs 10 Oct 2025 close.

While Perspective, whose 212Pb-VMT-α-NET failed to convince in phase 1/2, led the ESMO fallers this company is worth just $330m, and in terms of market cap changes there were far bigger moves on the back of ESMO.

Consider Summit, for instance, which not only upsized the Harmoni-3 trial of ivonescimab to bring forward readouts and give itself additional chances of success, but also revealed plans to file the anti-PD-1 x VEFG MAb on the back of Harmoni data – in spite of having been advised against this by the FDA in the absence of overall survival data.

The magic dust from Replimune suggesting that the FDA was becoming more receptive to suboptimal datasets failed to hit Summit, and the company fell 12%, including 15% over the ESMO weekend itself.

That amounted to about $2.5bn of market cap, while Genmab has lost an only slightly less alarming $1.1bn since 10 October. Genmab’s anti-FRα ADC rinatabart sesutecan now faces threats from two other similarly acting molecules profiled at ESMO – Lilly’s LY4170156 and Astra’s torvutatug samrotecan – while in head and neck cancer petosemtamab could be challenged by J&J’s Rybrevant.

Such competitor data could make Genmab’s acquisitions look reckless; rina-S came through the $1.8bn takeover of ProfoundBio, while petosemtamab is the lead asset of Merus, which Genmab is buying for $8bn. So confident is Astra, that torvuta-S will soon join LY4170156 in phase 3: a just revealed pivotal study will pit torvuta-S head to head against AbbVie’s Elahere.

Selected ESMO 2025 fallers

Note: *21 Oct 2025 close vs 10 Oct 2025 close.