this year. than $1 billion Sanofi between and Biond Biologics earlier as ILT2, of which potentially was focus the adeal worth more checkpoint inhibitor targets are attracting also interest, such to get afoothold fast-moving inthe emerging field. Other recentlyall potentially deals struck worth more than $1billion GlaxoSmithKline,trials, and have Gilead at front the of pack the with own their candidates inclinical 38, 1007–1009;2020).While and Merck &Co. are point target for reaches which adrug market the (Nat. Biotech. target TIGIT, which next the to is poised immune be check major companies access seeking to investigational that drugs checkpoint inhibitors year this alone. ing to Clarivate Analytics, were >100 deals involving signed populations that do not respond well to Indeed, them. accord apies could complement PD1/PDL1 inhibitors or reach patient evolves, for akey focus biopharma companies is how other ther mega-blockbusters.become As cancer the field ing products from Merck &Co. and Bristol Myers Squibb have have transformed treatment the of multiple cancers, and lead the In just a few years, PD1/PDL1 inhibitors Bhambra Raveena exemplified by therace to develop inhibitors oftheimmunecheckpointTIGIT. Next-generation immuno-oncology targets continue to catalyze majordeals, inhibitors checkpoint Chasing immune B42 |September 2021 | mAb, monoclonalantibody;TIGIT, Tcell immunoreceptor withIgandITIMdomains. Source: Clarivate Analytics, 2021. Table 1|Selected recent deals involving immunecheckpointinhibitors iTeos Therapeutics GlaxoSmithKline, Companies Squibb, Agenus Bristol Myers Biologics Biologics Sanofi, Biond Gilead, Arcus Several of largest the Several (Table 1) deals have driven by been June 2021 Date May 2021 2021 January May 2020 www.nature.com/biopharmdeal 2,000 value ($million) Potential deal 1,560 1,125 2,000 Deal summary studies withGlaxoSmithKline’s anti-PD-1 therapy Jemperli(dostarlimab) in2022. drug isbeingdeveloped for advanced solidtumors, andwillbetrialedincombination $625 millionupfront, to gain rightsto itsanti-TIGIT mAbEOS-448. The phase1 GlaxoSmithKline signsapotential $2billiondealwithiTeos Therapeutics, including marketing ofthecandidate. milestones. Bristol Myers Squibbwillberesponsible for development and $200 million upfront billionindevelopment andup to $1.36 andcommercial bispecific antibodythatblocks TIGITandasecond undisclosedtarget, for Bristol Myers Squibbpurchases anexclusive license to Agenus’ AGEN1777, a more than$1billioninpotential milestones. which isnow inphase 1.The dealincludesanupfront payment of$125millionand Sanofi acquires globalrights to theanti-ILT2 mAbBND-22 from BiondBiologics, $200 millionequity investment. non-small-cell lungcancer. Gileadagrees to pay $175 millionupfront alongwitha including itsanti-TIGIT mAbdomvanalimab, which isnow inphase3trialsfor Gilead signsaco-development andco-commercialization agreement withArcus, FEATURE - - - -

with PD1/PDL1 inhibitors and/or other anticancer drugs. clinical trials for multiple cancers as single agents or in combination checkpoint targets such as TIGIT are now being investigated in to build on their success. Drug candidates that inhibit further cancers for some subsets of patients, and intense efforts are ongoing approved. These have transformed the treatment of multiple the checkpoint protein PDL1 have PD1 or its binding partner been targets CTLA4 expressed on T cells—several inhibitors that target approval of the first checkpoint inhibitor in 2011—, which Fig. 1|Immunecheckpointtargets for cancer therapies. Since the (PDL1) PD1 CTLA4 Approved T cell Not yet approved CD96 TIGIT NKG2A LAG3 KIR BTLA TIM3 B7H3 ILT2

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