Bristol Myers Squibb has struck a deal to buy Forbius for its portfolio of TGF-beta inhibitors. The takeover will give Bristol Myers control of a clinical-phase inhibitor of TGF-beta 1 and 3 that Forbius is developing to increase the activity of immune checkpoint inhibitors.
TGF-beta is implicated in the inhibition of anti-cancer immunity in the tumor microenvironment and in the promotion of metastases. With researchers linking those effects to the failure of checkpoint inhibitors such as Bristol Myers’ Opdivo, Forbius advanced TGF-beta 1 and 3 inhibitor AVID200 into the clinic in treatment of refractory advanced and metastatic malignancies last year.
The work caught the attention of Bristol Myers, one of a clutch of leading oncology players that has been on the hunt for molecules that enhance the efficacy of checkpoint inhibitors. Bristol Myers is set to pay an upfront fee and milestones of undisclosed size to acquire Forbius.
Bristol Myers’ interest in Forbius primarily lies in the potential for AVID200 and the startup’s portfolio of earlier-stage TGF-beta inhibitors to improve outcomes in patients who don’t respond to existing immunotherapies such as Opdivo. The Big Pharma also sees scope to develop AVID200 and its sibling molecules in fibrosis, but it’s letting Forbius spin out its non-TGF-beta assets to form a new biotech.
The potential to improve outcomes in cancer patients by targeting TGF-beta has attracted some of Bristol Myers’ peers. Perhaps most notably, GlaxoSmithKline paid Merck KGaA €300 million ($355 million) upfront to jointly develop M7824, a bifunctional fusion protein immunotherapy that targets TGF-beta and PD-L1. A phase 3 trial comparing the drug to Merck’s Keytruda started in 2018.
Pfizer moved TGF-beta 1 inhibitor PF-06952229 into the clinic in advanced solid tumor patients in 2018. Scholar Rock began evaluating its prospect SRK-181 in combination with a checkpoint inhibitor in solid tumor patients this year.
The widespread interest in TGF-beta reflects the as-yet-untapped commercial opportunity for drugs that enable more people to respond to checkpoint inhibitors and evidence that the protein may be the key to unlocking those sales. In 2017, Roche shared bladder cancer data showing non-responders to its checkpoint inhibitor, Tecentriq, had high levels of TGF-beta. Roche followed up on that finding by linking the inhibition of TGF-beta in mice to increased Tecentriq efficacy.