Velosbio takes a different approach to Ror1

If, as many claim, Ror1 expression is restricted to cancerous and not normal cells this this receptor should be a popular oncology target. However, industry interest remains scarce, though yesterday one of the companies involved revealed early signs of promise. Velosbio, which last year raised $58m in a series A round led by Arix Bioscience, said it had treated 16 haematological cancer subjects with its anti-Ror1 antibody-drug conjugate VLS-101, and a very early case report yielded an unconfirmed partial remission in a heavily pretreated subject. At Arix’s capital markets day yesterday Dave Johnson, Velosbio’s chief executive, told Vantage that the source of VLS-101 was a deal with UCSD to develop the anti-Ror1 MAb cirmtuzumab as an ADC or bispecific. Oncternal, a company that Mr Johnson had chaired, is separately developing cirmtuzumab as a naked antibody coded UC-961. Perhaps the best-known Ror1-targeting project is Juno’s Car-T therapy JCAR024, based on a different, rabbit-derived MAb. It is not clear whether JCAR024 is a priority for Celgene, or indeed Bristol-Myers Squibb. And, while companies claim that Ror1 is a “clean” target, some research suggests its presence in multiple normal tissues. Velosbio hopes to announce full phase I data next year.

The Ror1 inhibitor pipeline
Company Project Pharmacology Status
Oncternal (ex UCSD) UC-961 (cirmtuzumab) Anti-Ror1 MAb Phase I/II (NCT03088878)
Celgene (ex Juno/Hutch) JCAR024 Anti-Ror1 Car-T therapy Phase I (NCT02706392)
Velosbio (ex UCSD) VLS-101 Anti-Ror1 ADC Phase I (NCT03833180)
None (MD Anderson) ROR1R-CAR-T  Anti-Ror1 Car-T therapy Phase I withdrawn (NCT02194374)
Aptevo ES425 Anti-Ror1 bispecific Preclinical
Kancera KAN0439834 Small-molecule Ror1 inhibitor Preclinical
Kancera KAN0441571 Small-molecule Ror1 inhibitor Preclinical
Macrogenics ROR-CD3 DART Program Anti-Ror1 bispecific Abandoned in preclinical?
Source: EvaluatePharma & clinicaltrials.gov.

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