Time for Nektar to Pivot

The most surprising thing about the latest failure of Nektar and Bristol Myers Squibb’s bempegaldesleukin is that it surprised investors. The former group’s stock opened down 52% this morning on news that the Pivot IO-001 trial, which was testing bempegaldesleukin plus Opdivo versus Opdivo alone in first-line melanoma, was a bust. Damningly, there was no benefit with the combo over Opdivo monotherapy on the co-primary endpoints of PFS and ORR, dealing another blow to the hypothesis that bempeg can turn cold tumours hot. Nektar has several more shots with the IL-2 project, but hopes must now be even lower than before, given that Pivot IO-001 is the latest of several flops. The group might be wise to shift focus to its Lilly-partnered autoimmune disease candidate NKTR-358, also an IL-2 agent; low doses of this cytokine are thought to activate immune-suppressing T regulatory cells. Phase 2 studies are ongoing in lupus and ulcerative colitis. At least Nektar has plenty of cash – $800m at the last count – thanks to its $1.85bn 2018 deal with Bristol. If IL-2 is confirmed as a complete dud, the many others in this space might not be so lucky.

Three failures and a discontinuation: the story so far with bempegaldesleukin 
Trial (ID) Setting Status
Pivot-02 (NCT02983045) + Opdivo in solid tumours Melanoma cohort disappointed in 2019
Propel (NCT03138889) + Keytruda in solid tumours Data in 1L NSCLC disappointed in 2021
Pivot IO-001 (NCT03635983) + Opdivo vs Opdivo alone in 1L melanoma Failed Mar 2022
Pivot-12 (NCT04410445) + Opdivo vs Opdivo alone in adjuvant melanoma Discontinued
NCT03729245 + Opdivo vs TKI in 1L RCC Data due H1 2022
Pivot-10 (NCT03785925) + Opdivo in 1L cisplatin-ineligible urothelial cancer Data due H1 2022
Propel (NCT03138889)* + Keytruda + chemo in 1L NSCLC Data due H2 2022
Propel-36 (NCT04969861) + Keytruda vs Keytruda alone in HNSCC Completes 2025
NCT04209114 + Opdivo vs Opdivo alone vs SOC in cisplatin-ineligible MIBC Completes 2026
*Expanded to evaluate bempeg, Keytruda and chemo; HNSCC=head and neck squamous cell carcinoma; NSCLC=non-small cell lung cancer; RCC=renal cell carcinoman; SOC=standard of care. Source: Evaluate Pharma & clinicaltrials.gov.

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