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No giving up on ROR1 for Oncternal

Oncternal, a small biotech whose pursuit of ROR1 blockade had piqued investors’ interest, is not giving up on this approach. Despite deprioritising its anti-ROR1 MAb zilovertamab earlier this year, the group is continuing to study ONCT-808, a Car-T therapy with the same mechanism, which it yesterday said should deliver its first clinical data by the end of this year. ONCT-808’s phase 1/2 trial started dosing in May, and tests three dose levels of a Car-T product manufactured at Dana Farber in patients with aggressive lymphoma who had failed, or are ineligible to receive, CD19-directed Car-T therapy. Major interest in ROR1 began in 2020 when Merck & Co paid $2.8bn to buy Velosbio, and shortly afterwards Boehringer Ingelheim acquired NBE-Therapeutics for up to $1.5bn. However, Bristol Myers Squibb last year discontinued the anti-ROR1 Car-T project JCAR024, which it had inherited from Juno/Celgene, while Kancera and Triumvira seem to have abandoned the preclinical assets KAN0439834/KAN0441571 and TAC01-ROR1 respectively.

 

Clinical-stage ROR1 inhibitors

ProjectCompanyModalityStatus
Zilovertamab vedotinMerck & Co (ex Velosbio)ADCPh2/3 in B-cell lymphoma
Zilovertamab (formerly cirmtuzumab)OncternalNaked MAbPh3 Imbruvica combo study withdrawn; ph2 Venclexta combo in CLL ongoing
BI 3702025/ NBE-002Boehringer Ingelheim (ex NBE-Therapeutics)ADCPh1/2 in solid tumours
ONCT-808OncternalCar-T therapyPh1/2 in B-cell malignancies, data by YE 2023
NVG-111NovalgenT-cell engagerPh1/2 in haematological cancers
GNC-035SystImmuneAnti-ROR1/PD-L1/CD3/4-1BB tetraspecific MAbPh1/2 in haematological cancers
RD14-01Zhejiang UniversityCar-T therapyPh1/2 in solid tumours
LCB71/ CS5001Legochem/ CstoneADCPh1 in solid tumours
LYL797Lyell ImmunopharmaCar-T therapyPh1 in solid tumours (2nd-gen LYL119 is preclinical)
PRGN-3007PrecigenCar-T therapyPh1 academic trial

Source: OncologyPipeline.