RE:RE:RE:RE:RE:Acceleron in advanced talks for $11 Bln sale - relationship
A further interest in combining the TGF-β antagonist with other IO agents like anti-PD-1 immune checkpoint inhibitors and potentially with ONCY's OV pelareorep follows the recent news that Merck KGaA’s biliary cancer hopeful bintrafusp alfa— a bispecific fusion protein comprises a Bavencio-like anti-PD-L1 linked to two molecules of TGF-β trap and at the heart of a $4.2 billion deal with GlaxoSmithKline - folows the failure of bintrafusp alfa in first line lung cancer and later in biliary cancer.
The theory for the use of bintrafusp alfa ran that such a dual mechanism, active in the tumour microenvironment, could block innate and adaptive immunity. TGF-β is a cytokine associated with local immunosuppression, and the idea was that trapping it in the microenvironment could improve on the activity of PD-L1 blockade alone.
This bispecific fusion protein's failure demonstrates that rather than blocking he innate and adaptive immune system, the opposite effect of activating both the innate and adaptive system thus enhances the immune system is the better solution to killing cancer.
Consequently, ONCY's OV pelareorep could instead influence the success of a TGF-β antagonist/anti-PD-1 bispecific (unlike that of a TGF-β trap) by pelareorep's ability to improve the activity of PD-1 blockade by acting synergistically with immune checkpoint inhibitors (ICIs) to improve their effectiveness and reverse the issues of T-cell exhaustion and checkpoint inhibitor resistance in the TME.