Instil Bio has been a biotech in search of a pipeline after it scrapped its lead assets over the last couple of years. Now, it seems to have found a pair of clinical-stage candidates from China to instill it with new purpose.
The Dallas-based biotech is paying $50 million in upfront and near-term payments—with potentially up to $2 billion to follow in milestones—to China’s ImmuneOnco Biopharmaceuticals for therapies dubbed IMM2510 and IMM27M.
IMM2510 is a bispecific antibody combining an anti-PD-L1 antibody with a vascular endothelial growth factor (VEGF) receptor “trap” that binds VEGF. Academic researchers have already shown that anti-PD-1 therapy together with anti-VEGF can effectively block the PD-1/PD-L1 axis and synergistically suppress tumor growth, especially when it comes to tumors with VEGF hypersecretion.
According to the two companies, what sets IMM2510 apart from other PD(L)1xVEGF antibodies in development is its ability to bind multiple VEGF receptor ligands beyond VEGF-A.
VEGF-A is a protein known to stimulate the formation of blood vessels. Roche’s eye disease blockbuster Vabysmo suppresses VEGF-A, while at one point Moderna and AstraZeneca were looking at an mRNA cardiovascular drug with the same target.
The companies also said that IMM2510 has a “smaller molecular weight allowing for potentially better tumor penetration, and enhanced antibody-dependent cellular cytotoxicity designed to improve tumor killing.”
IMM2510 has completed a phase 1 dose-escalation trial in advanced solid tumors, where it demonstrated a response in the likes of patients with squamous non-small cell lung cancer whose cancer had not been effectively treated by PD-1 inhibitors.
The other candidate helping to fill out Instil’s empty pipeline, IMM27M, is a next-generation anti-CTLA-4 antibody that the companies said has been designed to “promote intratumoral regulatory T cell depletion to enhance the efficacy and reduce the toxicity associated with first-generation anti-CTLA-4 antibodies.”
As well as completing a phase 1 dose-escalation study of IMM27M to show its anti-tumor potential, ImmuneOnco also launched a trial last month to assess the anti-CTLA-4 antibody in combination with IMM2510.
The deal terms mean Instil will gain the rights to both candidates everywhere outside of greater China. On top of the combined $2.05 billion in biobucks up for grabs, ImmuneOnco will also be in line for low double-digit percentage royalties on sales.
Instil needed to restock its pipeline after the biotech scrapped its lead tumor-infiltrating lymphocyte therapy and four corresponding programs—along with 60% of its staff—at the end of 2022. That left the company with only its ITIL-306 program, but the company announced earlier this year that even this was being shut down.