Instil’s bispecific dream is over
The company hands its PD-L1 x VEGF bispecific back to ImmuneOnco.
The company hands its PD-L1 x VEGF bispecific back to ImmuneOnco.
As companies continue to pile into the PD-(L)1 x VEGF space, one group that will no longer be participating is Instil Bio. The company disclosed on Tuesday that it had discontinued development of its contender, palverafusp alfa (AXN-2510), and returned rights to its originator, ImmuneOnco. Instil has also given back tazlestobart (AXN-27M), an anti-CTLA-4 antibody.
Instil, via its Axion Bio subsidiary, licensed both projects in August 2024 for just $10m up front, according to SEC filings – this is even cheaper than the $50m in “up-front and potential near-term payments” cited at the time.
Ever since, investors have wondered whether the deal was so cheap because Instil got in ahead of the PD-(L)1 x VEGF craze, or because palverafusp alfa was no good. The latest development suggests the latter to be the case. Instil's stock closed down 46% on Tuesday.
No reason
Instil hasn’t given a reason for its latest decision, but there have been some clues that all might not be well. In July, Chinese phase 2 data with a palvera/chemo combo in first-line lung cancer looked lacklustre in a cross-trial comparison with Roche’s Tecentriq plus Avastin plus chemo – at least in non-squamous patients.
Still, at World Lung a poster showed a 35% ORR among 17 squamous post-PD-(L)1 inhibitor patients who received palvera monotherapy in a Chinese phase 1 study. This looks favourable compared with the control arm of Tropion-Lung01, which in the squamous population found an ORR of 13% with docetaxel in second-line squamous NSCLC.
Perhaps some new toxicity signal has emerged. Until now, Instil appeared to be pressing ahead with the project, starting a US phase 1 trial of palvera in September, and dosing the first patient in October.
The Axion subsidiary is being wound down, but it’s unclear what Instil might do next. As of September, the company had cash and equivalents of $83.4m; at the time, it estimated that this would keep it going “beyond 2026”.
Instil's move for palvera marked a pivot from TIL therapies, and it looks like the group might now need to change focus again. The company's pipeline is now bare, so offering itself as a listed shell for a private entity to reverse into might be Instil's only hope.
1895
