Abstract PS4-04-21: Deciparticle™ Everolimus (Sapu003): From Cytostasis to Cytotoxicity via a Single mPEG Polymer and Clinic-Ready Manufacturing

Abstract Background: Everolimus is approved for advanced renal-cell carcinoma following VEGF-targeted therapy, for metastatic HR-positive/HER2-negative breast cancer in combination with exemestane, and for other oncology indications. However, everolimus lacks an intravenous option due to its extreme hydrophobicity, despite its low oral bioavailability of only 15-20%. Here, we describe the successful development of an intravenous formulation of Everolimus using our Deciparticle™ platform. Formulation: A 38-member mPEG-block polymer library was screened as potential candidates for encapsulating Everolimus. Nine polymers demonstrated the ability to form stable Deciparticles™. Among these candidates, VT111 was selected based on its favorable biocompatibility. VT111 and its variants were able to formulate both peptides and polyketides, including Everolimus, Sirolimus, Tacrolimus, and Cyclosporine. Manufacturing: Clinical lots were produced using a 7-day process at our cGMP facility. The manufacturing process began with the dissolution of VT111 and Everolimus in ethanol, which was subsequently solubilized into lactose and Water for Injection to form Deciparticles™. The process was conducted under yellow light and utilized amber vials to minimize Everolimus degradation. The bulk drug was filter sterilized. Fill/finish operations were in a temperature-controlled environment with ≥98% filling weight accuracy. The drug product was reconstituted to a final concentration of 4 mg/mL for intravenous administration. Upon reconstitution, the product yielded monodisperse Deciparticles™ that met sterility and particle-size specifications and remained within specifications for at least one month at 5 °C storage and for at least 24 hours of in-use stability at 25 °C. The same process has been successfully scaled to over 10 g, sufficient for Phase 1 clinical supply. In Vivo Activity: Sapu003 exhibited potent antitumor activity in vivo (IV, BIW × 4) and demonstrated tumor growth inhibition (TGI) percentages of: U-87 MG glioblastoma (TGI 97-98%), HT-29 colorectal cancer (71-73%), OVCAR-3 ovarian cancer (66%), and MDA-MB-231 breast cancer (48%). No phlebitis was observed during repeated tail-vein administrations. Sapu003 sensitivity correlated with glycolytic dependence (U-87 ≫ HT-29 > OVCAR-3 ≈ MDA-MB-231). In the glycolysis-dependent U-87 model, Sapu003 was cytotoxic and outperformed paclitaxel, without inducing body weight loss. Conclusions: We screened a 38-member mPEG-block polymer library for self-assembling capacity and identified a leading candidate, VT111, which reproducibly formed stable Deciparticles™ under 20 nm in mean particle diameter and demonstrated potent antitumor activity across multiple xenograft models. VT111 uniquely defines the chemical space for Deciparticle™ technology and enables a reproducible cGMP process yielding a long-term stable drug product. These data could support the ongoing first-in-human study of weekly Sapu003 and open the Deciparticle™ platform to other water-insoluble oncology agents. Citation Format: S. Min, K. Forero, J. Anderson, W. Putnam, C. Evizi, C. McCallum, R. Hoff, C. Hsieh, K. Ho. Deciparticle™ Everolimus (Sapu003): From Cytostasis to Cytotoxicity via a Single mPEG Polymer and Clinic-Ready Manufacturing [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-04-21.