Abstract 1809: The role of HyDIFFUZETM in co-formulation with subcutaneous infliximab

Abstract Background: Recombinant human Hyaluronidase PH20 (rHuPH20) is an enzyme that degrades subcutaneous (SC) hyaluronan and has been used as a drug dispersion agent to optimize the SC delivery of co-formulated therapeutic antibodies. HyDIFFUZETM, a stand-alone rHuPH20 is under development as a dispersion agent and tissue permeation modifier for co-formulated drugs in the stage of the registration study(N=243) in S. Korea. Recently, SC formulation of Infliximab, a tumor necrosis factor inhibitor, has been approved for the treatment of autoimmune diseases. Although the therapeutic response to infliximab is strongly associated with drug exposure, the effect of HyDIFFUZETM on absorption and therapeutic response of co-formulated infliximab remains unclear. The purpose of the study was to demonstrate the applicability of HyDIFFUZETM as an effective drug dispersion agent by evaluating the effects of HyDIFFUZETM on the pharmacokinetics (PK) of co-formulated infliximab, compared to SC infliximab alone. Methods: To investigate whether HyDIFFUZETM enhances dispersion of infliximab, PK of infliximab was analyzed after SC injection along with HyDIFFUZETM and compared with that of infliximab without HyDIFFUZETM. A single dose was administered to SD rats (n=5/group), and blood samples were collected at 12 time points over 28 days post injection. Plasma concentrations of infliximab were determined using ELISA and PK parameters were obtained by Phoenix WinNolin. Results: In vivo PK studies showed that formulation of 84 mg/kg Infliximab combined with 1400 unit/kg HyDIFFUZETM resulted in AUCt 127.2% and Cmax 119.9%, compared to 84 mg/kg infliximab without HyDIFFUZETM. Furthermore, PK profiles of 63 mg/kg infliximab with HyDIFFUZETM similar to that of 84 mg/kg infliximab alone with AUCt 105.5% and Cmax 95.1%. These results suggest that HyDIFFUZETM might reduce the dose of infliximab required to generate equivalent therapeutic effects. Increasing the dose of Infliximab/HyDIFFUZETM resulted in a greater-than-dose-proportional increase in AUCt, Cmax, and T1/2, indicating enhanced systemic drug exposure. Additionally, SC formulated of 168 mg/kg infliximab with HyDIFFUZETM showed an AUCt approximately 90% of that achieved with IV injection of 60 mg/kg infliximab. Conclusions: This study demonstrated that the HyDIFFUZETM significantly enhanced intravascular uptake of infliximab, with sustained therapeutic plasma concentrations of Infliximab observed over an extended duration as the dose increased. These findings suggest that combining infliximab with HyDIFFUZETM may allow enhanced systemic drug exposure even at lower dose sand potentially extend dosing intervals. Furthermore, the results presented the possibility that SC infliximab/HyDIFFUZETM may potentially replace intravenously (IV) infliximab in the induction regimen resulting in an entire treatment of induction and maintenance with SC infliximab/HyDIFFUZETM only. Citation Format: Younseo Oh, Hyungip Kim, Heeyoun Kim, Donghwan Kim, Boyoung Park, Juyoung Byun, Chaeyoung Lim. The role of HyDIFFUZETM in co-formulation with subcutaneous infliximab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1809.