sirolimus (Excel / Excel II)

Topical Sirolimus Therapy for Agminated Pyogenic Granulomas: A Two-Case Report.

Van Matre Stetson S, Hicks Evan E, Richter Gresham T GT, Mack Joana J

Pyogenic granulomas (PGs) are benign vascular tumors that present as rapidly growing, friable papules that often bleed and cause cosmetic disfigurement. PGs generally respond well to treatments such as excision, laser, cryotherapy, topical imiquimod, and topical timolol, but agminated PGs can be distressing to patients and challenging to treat. Topical sirolimus, an mTOR inhibitor, is used in the treatment of other vascular anomalies but has not been previously investigated for use in PGs. We report two patients with agminated PGs who demonstrated improvement in size, color, and bleeding following treatment with topical sirolimus.

Intestinal failure in kaposiform hemangioendothelioma successfully resolved with medical therapy and nearly fat-free oral feeding: A novel case report.

Mosher Tierra L TL, Contijoch Eduardo J EJ, Bui Jordan J, Teng Joyce J et al.

Kaposiform hemangioendothelioma and kaposiform lymphangiomatosis (KHE/KLA) are rare, non-malignant lymphovascular anomalies often complicated by Kasabach-Merritt phenomenon (KMP). Morbidity and mortality are high. There are no prior reports of the dietary management in these disorders. A 2-month-old female presented with hemorrhagic ascites, abdominal compartment syndrome, and severe KMP secondary to extensive retroperitoneal and intestinal KHE/KLA. Following emergent surgical management for abdominal decompression and diverting ileostomy, medical and nutritional therapy with steroids, vincristine, sirolimus, and parenteral nutrition were employed for management. After maintaining a near fat-free enteral diet supplemented with intravenous lipid therapy in the outpatient setting, she underwent successful ileostomy takedown 18 months after initial diagnosis without the need for intestinal resection and maintenance of adequate growth. This case underscores the value of clinical and pathology-guided diagnosis, coordinated medical therapy, and dietary fat restriction for achieving intestinal autonomy and preserving bowel length in intra-abdominal KHE/KLA.

Intravenous Everolimus Formulation (Sapu003) for Clinical Trials.

Min Sheng-Hao SH, Forero Kevin K, Putnam William W, Anderson Jonathan J et al.

Everolimus is approved for the treatment of advanced renal cell carcinoma after VEGF-targeted therapy, metastatic HR-positive/HER2-negative breast cancer in combination with exemestane, and other oncologic indications. However, an intravenous option has not been developed, largely due to its pronounced hydrophobicity and limited oral bioavailability of approximately 15-20%. In this study, we report the development of Sapu003, a novel intravenous Everolimus formulation enabled through the Deciparticle™ platform. A diverse library of mPEG-based block copolymers was evaluated for their ability to encapsulate Everolimus and self-assemble into stable nanoparticle structures. mPEG-Chol was ultimately selected based on its favorable biocompatibility characteristics. In addition to Everolimus, mPEG-Chol and related analogs demonstrated broad formulation compatibility with multiple hydrophobic therapeutics, including Sirolimus, Tacrolimus, Cyclosporine, as well as representative peptides and polyketides. Clinical manufacturing was conducted in a cGMP environment over a 7-day production cycle. Production was carried out under amber light using light-protective vials to reduce drug degradation. The bulk material was sterile-filtered, and subsequent fill/finish/lyophilization operations were performed under temperature-controlled conditions with high precision in fill accuracy (≥98%). After reconstitution, the final product yielding uniform Deciparticles™ that met predefined sterility and particle size criteria. Stability studies demonstrated that the formulation remained stable for at least one month at 5 °C and retained acceptable in-use stability for at least 24 h at room temperature. The process was successfully scaled beyond 10 g, supporting an ongoing Phase 1b open-label dose escalation clinical study of Sapu003 in combination with exemestane in patients with advanced mTOR-sensitive solid tumors (NCT07369505). In vivo evaluation demonstrated strong antitumor efficacy following intravenous administration (QW × 3), with tumor growth inhibition reaching 97-98% in the U-87MG glioblastoma xenograft model. No evidence of phlebitis was observed with repeated tail vein dosing. In this model, Sapu003 dosed weekly showed superior tumor suppression compared with oral Everolimus. Collectively, screening of a mPEG-block copolymer library identified mPEG-Chol as a lead excipient capable of consistently forming stable Deciparticles™ with sub-20 nm mean particle size. The resulting intravenous Everolimus formulation demonstrated scalable manufacturing, favorable stability, and potent antitumor activity in preclinical models, supporting further clinical evaluation of Sapu003 in advanced solid tumors.

Response to Comment on: "Sirolimus versus mycophenolate mofetil for the treatment of lupus nephritis: Results from a real-world CSTAR cohort study".

Bai Wei W, Li Mengtao M