Jounce trounced after Icos stumble

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Targeting Icos has looked like a questionable strategy for some time. Now the failure of Jounce’s vopratelimab in the phase II Emerge trial has put the spotlight on another champion of this approach: Glaxosmithkline. A big test for Glaxo’s own Icos agonist, GSK3359609, is coming up, with data from the phase II Entrée trial in non-small cell lung cancer due in the first half of 2021. Glaxo is claiming its project is differentiated as it causes no or minimal T-cell depletion. Still, the signs are not good. Jounce had to stop Emerge after an interim analysis found that vopratelimab plus Yervoy did not show a benefit in PD-(L)1 inhibitor experienced NSCLC patients. The company will hope for a better result in the Select study of vopratelimab with its PD-1 inhibitor, JTX-4014, in PD-(L)1-naïve NSCLC – however, hopes cannot now be high, especially after a similar combo, vopratelimab plus Opdivo, disappointed in the Iconic study in various cancer types. Jounce has a couple more preclinical assets in its pipeline, with Gilead recently licensing the CCR8-targeting JTX-1811; however, Bristol Myers Squibb returned rights to the anti-leukocyte immunoglobulin-like receptor B2 antibody JTX-8064 in June. Jounce stock closed down 18% yesterday.

Selected company-sponsored trials of Icos-targeting projects in oncology
Project Company Indication Trial details Data due
GSK3359609 Glaxosmithkline Head & neck cancer Ph3 Induce-3 (NCT04128696) & Induce-4 (NCT04428333) + Keytruda Ends 2023/2024
    NSCLC Ph2 Entrée (NCT03739710) + docetaxel vs docetaxel alone  H1 2021
JTX-2011 Jounce Therapeutics NSCLC Ph2 Emerge (NCT03989362) + Yervoy in PD-(L)1-experienced pts Failed
    Ph2 Select (NCT04549025) + JTX-4014 in PD-(L)1-naïve pts Ends 2021
BMS-986226 Bristol Myers Squibb Solid tumours Ph1/2 (NCT03251924) alone or + Opdivo/Yervoy Ends 2022
XmAb23104* Xencor Solid tumours Ph1 Duet 3 (NCT03752398) Ends 2024
*Icos + PD-1 bispecific. Source: EvaluatePharma, clinicaltrials.gov.

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