Oruka Therapeutics announces preclinical data for ORKA-001

Oruka Therapeutics announced new preclinical data on ORKA-001, a novel extended half-life monoclonal antibody targeting IL-23p19, from its presentation at the European Academy of Dermatology and Venereology Congress. ORKA-001 has an NHP half-life of 30.3 days following SQ administration and 33.8 days following IV administration, over three times longer than risankizumab and one of the longest NHP half-lives observed for an extended half-life antibody. Projections of ORKA-001 pharmacokinetics in humans indicate that a human half-life of approximately 50 days could enable dosing once every six months, while a human half-life of approximately 75 days could enable once-yearly dosing. The NHP half-life observed for ORKA-001 supports the potential to achieve these extended dosing intervals given that other YTE-modified antibodies have had an approximately two to four times longer half-life in humans than in NHPs. In addition, the extended half-life of ORKA-001 could result in higher antibody exposures than risankizumab, which could lead to greater efficacy. ORKA-001 binds to a similar epitope with similar affinity to risankizumab and shows equivalent potency across a variety of in vitro assays. ORKA-001 binds IL-23p19 with an affinity below five picomolar. Based on cryo-EM structural analysis, ORKA-001 binds to a nearly identical epitope to risankizumab. When assessed across four different assays in cell lines and primary cells, ORKA-001 also had comparable functional potency for IL-23 antagonism. These findings support that ORKA-001 has a validated mechanism of action and further derisk its development path.