everolimus injection (Sapu003) / GMP Biotech, Oncotelic, Sapu Nano - LARVOL DELTA

IV-EVE: EVE for Injection-ADME, Pharmacokinetic and Toxicological Evaluation for Novel Deciparticle EVE Formulation. (PubMed, Biomedicines) - "Background: Oral everolimus (Oral-EVE; EVE, Afinitor®) is an effective therapy for multiple malignancies, including HR-positive/HER2-negative breast cancer, but its clinical use is limited by low and variable oral bioavailability as well as extensive first-pass metabolism. Repeat-dose toxicology studies in rats demonstrated no treatment-related gastric pathology following intravenous administration. These findings suggest that intravenous administration may overcome limitations associated with oral delivery and support the clinical evaluation of IV-EVE in patients with advanced malignancies."

Journal • PK/PD data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Oncotelic Therapeutics…and Sapu Nano today announced the publication of a comprehensive peer-reviewed study in Biomedicines describing the preclinical translational package supporting Sapu003, the Company's intravenous Deciparticle formulation of everolimus (GlobeNewswire) - "The publication provides a complete evaluation of the formulation's absorption, distribution, metabolism, excretion (ADME), pharmacokinetics (PK), tissue distribution, GLP toxicology, and cGMP manufacturing, representing one of the most comprehensive nonclinical evaluations reported for an intravenous formulation of everolimus. The study demonstrates that Deciparticle technology successfully transforms everolimus from an oral therapy with well-recognized pharmacokinetic limitations into a clinically manufacturable intravenous formulation while preserving the drug's intrinsic metabolic characteristics."

Preclinical • Oncology

Intravenous Everolimus Formulation (Sapu003) for Clinical Trials. (PubMed, Int J Mol Sci) - P1 | "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...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...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."

Journal • Brain Cancer • Breast Cancer • Genito-urinary Cancer • Glioblastoma • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • HER-2

Sapu Nano…announced that the independent Safety Review Committee (SRC) has completed its review of the initial safety cohort in the Company's ongoing SP-03-B101 Phase 1b clinical trial evaluating Sapu003, an investigational intravenous formulation of everolimus. (Malay Mail) - "Following completion of the protocol-defined 28-day dose-limiting toxicity (DLT) evaluation period for the initial three-patient cohort, the SRC concluded that no dose-limiting toxicities were observed and recommended advancing the study to the next planned dose level. Enrollment into the second dose cohort has commenced...Following successful completion of the initial safety cohort, the Company has initiated expansion of the SP-03-B101 clinical program into Europe, broadening patient access and supporting the global clinical development strategy for Sapu003."

Trial status • Hepatocellular Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Neuroendocrine Tumor • Renal Cell Carcinoma

Sapu Nano and Oncotelic Therapeutics…announced the expansion of its Phase 1b clinical development program for Sapu003 (Everolimus for Injection) and the appointment of Global Clinical Trials (GCT) as the lead contract research organization supporting international execution of Study SP-03-B101 (GlobeNewswire) - "Following its appointment, GCT successfully completed key regulatory submissions ahead of schedule and has initiated clinical operations, regulatory coordination, site activation activities, investigational product logistics, and study management functions. The appointment supports the expansion of the SP-03-B101 study beyond Australia into Europe and represents an important step in establishing the clinical, operational, and regulatory infrastructure necessary to support future multinational Phase 3 development....SP-03-B101 is an open-label Phase 1b dose-escalation study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of Sapu003 in patients with advanced mTOR-sensitive solid tumors."

Licensing / partnership • Trial status • Solid Tumor

Sapu Nano Announces First Patient Dosed in Phase 1b Trial of Sapu003, an Intravenous Deciparticle Formulation of Everolimus (GlobeNewswire) - "The trial: SP-03-B101 - Sapu003 in Patients with Advanced mTOR-sensitive Solid Tumors (NCT07369505), is a Phase 1b, open-label, dose-escalation trial designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of Sapu003 in patients with advanced mTOR-sensitive solid tumors....The study includes two cohorts. Cohort A enrolls patients with HR-positive/HER2-negative breast cancer, receiving Sapu003 in combination with endocrine therapy. Cohort B enrolls patients with renal cell carcinoma, neuroendocrine tumors, TSC-associated tumors, or hepatocellular carcinoma, receiving Sapu003 as monotherapy."

Trial status • Hepatocellular Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Neuroendocrine Tumor • Renal Cell Carcinoma

Oncotelic Therapeutics Joint Venture Identifies Biomarker Signature Predicting Tumor Sensitivity to IV Sapu003 (City Buzz) - "Data show that mTORC2-dominant tumors exhibit heightened mTOR dependency and predicted sensitivity to Sapu003. These tumors include HR+/HER2- breast cancer, lung adenocarcinoma, gastric cancer, renal cancer, ovarian cancer, acute myeloid leukemia (AML), and T-cell malignancies."

Biomarker • Clinical data • Acute Myelogenous Leukemia • Gastric Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Adenocarcinoma • Ovarian Cancer • Renal Cell Carcinoma

Oncotelic and Sapu Nano Announces New PK Data Demonstrating IV Sapu003 Reduces GI Accumulation of Everolimus up to 67-Fold Compared With Oral Dosing (GlobeNewswire) - "New tissue-distribution data show that Sapu003, delivered intravenously, eliminates the extreme gastrointestinal accumulation characteristic of oral everolimus. After oral dosing, everolimus reaches 2,448× plasma levels in the stomach, 750× plasma in the small intestine, and 323× plasma in the large intestine, confirming that the gut is the dominant exposure site for the oral formulation...In contrast, IV Sapu003 demonstrates only 36–48× plasma levels across the same GI tissues, representing a 67-fold reduction in stomach exposure, a 15.7-fold reduction in small-intestinal exposure, and a 7.4-fold reduction in large-intestinal exposure....These findings provide a clear mechanistic explanation for the well-documented GI toxicity of oral everolimus—including stomatitis, mucositis, abdominal discomfort, and diarrhea."

PK/PD data • Preclinical • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Sapu Nano to present at the 2025 San Antonio Breast Cancer Symposium (SABCS) Highlighting Sapu003 (Deciparticle Everolimus) (GlobeNewswire) - "Collectively, the accepted abstracts highlight the clinical rationale, molecular biomarkers, and pharmacokinetic justification supporting the ongoing Phase 1 trial of Sapu003 in hormone receptor–positive (HR⁺)/HER2⁻ metastatic breast cancer and RCC and NET."

Biomarker • P1 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Neuroendocrine Tumor • Renal Cell Carcinoma

Oncotelic to present at the 2025 San Antonio Breast Cancer Symposium (SABCS) Highlighting Sapu003 (Deciparticle Everolimus) (GlobeNewswire) - "Collectively, the accepted abstracts highlight the clinical rationale, molecular biomarkers, and pharmacokinetic justification supporting the ongoing Phase 1 trial of Sapu003 in hormone receptor–positive (HR⁺)/HER2⁻ metastatic breast cancer."

Biomarker • Clinical data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Sapu Nano Unveils First-in-Human Clinical Trial of Sapu-003 at 8th Australian Translational Breast Cancer Research Symposium (GlobeNewswire) - "The trial (ACTRN12625001083482) is now open for enrollment at leading oncology centers across Australia. Eligible participants include adults with advanced HR+/HER2– breast cancer or other mTOR-sensitive tumors who have exhausted standard therapies. Physicians are encouraged to refer patients who may benefit from participation."

Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Sapu Nano has received approval from Australia’s Human Research Ethics Committee to begin enrolling patients in clinical trials for Sapu003, an injectable form of Afinitor (Everolimus) for breast cancer treatment (City Buzz)

New trial • Breast Cancer