Bayer’s $1.5bn acquisition of Vividion in 2021 was a huge bet on ways to treat NRF2-driven cancers, especially since the target was a low-profile, preclinical-stage biotech. The takeover could soon see clinical validation as Vividion today said it had dosed the first patients in a phase 1 trial of its lead asset, the KEAP1-activator VVD-130037. KEAP1 is a negative regulator of NRF2, being involved in maintaining intracellular redox homeostasis, and NRF2 inhibition and KEAP1 activation can be seen as anticancer mechanisms. Vividion, which like Bayer’s cell and gene therapy units is run at arm’s length as a separate division, claims that VVD-130037 is a first-in-class clinical candidate to target cancers with activation of the KEAP1/NRF2 pathway, though other companies have been here before. Among projects targeting this pathway, Novartis’s MGY825, in a phase 1 study in lung cancer with mutations including KEAP1, is perhaps the biggest competitor to Vividion’s work, OncologyPipeline reveals. Since KEAP1 mutations are thought to increase cells’ dependence on glutamine, glutaminase inhibitors were once also thought capable of hitting the KEAP1/NRF2 pathway, though the three prominent clinical projects here have recently been discontinued.Selected industry projects with activity on NRF2-driven cancersProjectMechanism of actionCompanyStatusSulforadex (SFX-01)NRF2 activatorEvgen PharmaPh2 breast cancer trial completedTelaglenastatGlutaminase inhibitorCalitheraPh2 in NSCLC with KEAP1/NRF2 mutation terminatedMGY825NFE2L2/KEAP1/CUL3 inhibitorNovartisPh1 in NSCLC with NFE2L2, KEAP1 or CUL3 mutationsVVD-130037KEAP1 activatorVividion (Bayer)Ph1 solid tumour trial started 2023Sirpiglenastat (DRP-104)Glutamine antagonistDracen PharmaceuticalsPh1 solid tumour trial terminatedIPN60090Glutaminase inhibitorIpsenPh1 solid tumour trial terminated; preclinical data in KEAP1/NFE2L2 mutated NSCLC at AACR 2020DRP-NRF2NRF2 inhibitorDracen PharmaceuticalsPreclinicalK1.1 mRNAAnti-NRF2 mRNA vaccineSunshine BiopharmaPreclinicalTellBio-XXKEAP1 regulatorTellBioPreclinicalYD0514NRF2/RHOA/ROCK inhibitorMD Anderson Cancer CenterPreclinicalMSU38225/ MSU225NRF2 inhibitorMichigan State UniversityPreclinicalIMR-261 (CXA-10)NRF2 activatorEnliven TherapeuticsDiscontinued in 2023 (preclinical)Source: OncologyPipeline.
Bayer’s $1.5bn acquisition of Vividion in 2021 was a huge bet on ways to treat NRF2-driven cancers, especially since the target was a low-profile, preclinical-stage biotech. The takeover could soon see clinical validation as Vividion today said it had dosed the first patients in a phase 1 trial of its lead asset, the KEAP1-activator VVD-130037. KEAP1 is a negative regulator of NRF2, being involved in maintaining intracellular redox homeostasis, and NRF2 inhibition and KEAP1 activation can be seen as anticancer mechanisms. Vividion, which like Bayer’s cell and gene therapy units is run at arm’s length as a separate division, claims that VVD-130037 is a first-in-class clinical candidate to target cancers with activation of the KEAP1/NRF2 pathway, though other companies have been here before. Among projects targeting this pathway, Novartis’s MGY825, in a phase 1 study in lung cancer with mutations including KEAP1, is perhaps the biggest competitor to Vividion’s work, OncologyPipeline reveals. Since KEAP1 mutations are thought to increase cells’ dependence on glutamine, glutaminase inhibitors were once also thought capable of hitting the KEAP1/NRF2 pathway, though the three prominent clinical projects here have recently been discontinued.
Selected industry projects with activity on NRF2-driven cancers
