Before Covid-19 threw a hand grenade into the global economy many investors were looking to bispecific antibodies to prove themselves the equal of cell therapy. This is still some way off, but the promise is apparently sufficient to keep business development moving.
Just today Cytomx struck a T-cell engager alliance with Astellas, its fourth partner, worth $80m up front – a considerable sum for what is merely a discovery tie-up. And another player, Pieris, saw the tectonic plates in its alliance with Servier shift to focus on two defined bispecific assets.
While Cytomx and Pieris both have a presence in bispecifics their focus differs. The former is active largely in T-cell engaging MAbs, designed to bring a T cell into close contact with the antigen-expressing tumour cell, and indeed this is the focus of the Astellas deal.
The Japanese group agreeing to hand across $80m on signing might be the result of biotechs pushing for instant cash, given that the Covid-19 pandemic has turned the economy into a survival of the fittest where cash is king. Then again, at $1.6bn the deal’s biodollar value is not to be sniffed at either.
Mizuho analysts called Astellas’s endorsement a validation of the Probody approach’s commercial potential. Probody therapeutics are designed to remain dormant until they are activated by proteases in the tumour microenvironment, Cytomx says.
Perhaps the best-known Probody is not a bispecific, but the CTLA-4-targeting BMS-986249, now in phase I/II under Cytomx’s deal with Bristol-Myers Squibb. In addition to Bristol, and now Astellas, Cytomx has signed deals with Abbvie and Amgen.
Dual antigen approach
Pieris’s bispecific focus, meanwhile, is on molecules that hit two distinct antigens, and Servier had bought into this concept back in January 2017 in a tie-up worth €30m ($33m) up front.
At the time this centred around PRS-332, an anti-PD-1/Lag-3 bispecific, and four other undisclosed assets, but last September Servier discontinued PRS-332, citing “strategic reasons”. The deal was then extended for an additional year, and yesterday came news that the French firm had decided to focus its interest on two Pieris assets: PRS-344 and PRS-352.
The former is an a bispecific agonising 4-1BB and antagonising PD-L1. Such a mechanism risks undesirably broad immune system activation, and Pieris stresses that the effect on 4-1BB is “localised”, aiming to give T cells a long-lived phenotype.
The mechanism of PRS-352 has not been disclosed, and neither has that of the deal’s remaining two molecules, which Servier is discontinuing and which are reverting to Pieris. An IND for PRS-344 is to be filed shortly, but given the coronavirus pandemic when it might enter the clinic is anyone’s guess.