Promitil (pegylated liposomal mitomycin-c prodrug) / LipoMedix - LARVOL DELTA

Promitil Treatment of Patients With Solid Tumors Associated With Deleterious Mutations Who Have Progressed After Therapy (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Lipomedix Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • BRCA

Promitil Treatment of Patients With Solid Tumors Associated With Deleterious Mutations Who Have Progressed After Therapy (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Lipomedix Pharmaceuticals Inc.

New P2 trial • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • BRCA

PROMIFOX: Assessment of Safety and Therapeutic Efficacy of Promitil in Combination With Folfox in Patients With GI Malignancies (clinicaltrials.gov) - P1b | N=9 | Terminated | Sponsor: Lipomedix Pharmaceuticals Inc. | Trial completion date: May 2023 ➔ Sep 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Mar 2023 ➔ Sep 2023; Investigational drug not available

Combination therapy • Trial completion date • Trial primary completion date • Trial termination • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Pegylated liposomal mitomycin C lipidic prodrug in combination with external beam radiotherapy in patients with advanced cancer: a Phase 1B study. (PubMed, Int J Radiat Oncol Biol Phys) - "PL-MLP up to 1.8 mg/kg in combination with RT treatment is safe, with a high rate of tumor control. Drug clearance is not affected by radiation. PL- MLP is potentially an attractive option for chemoradiotherapy that warrants further evaluation in randomized studies in the palliative and the curative settings."

Combination therapy • Journal • Metastases • P1 data • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

PROMIFOX: Assessment of Safety and Therapeutic Efficacy of Promitil in Combination With Folfox in Patients With GI Malignancies (clinicaltrials.gov) - P1b | N=9 | Active, not recruiting | Sponsor: Lipomedix Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2022 ➔ May 2023 | Trial primary completion date: Sep 2022 ➔ Mar 2023

Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Liposome co-encapsulation of anti-cancer agents for pharmacological optimization of nanomedicine-based combination chemotherapy. (PubMed, Cancer Drug Resist) - " We have developed several liposome formulations of co-encapsulated drugs using various permutations of three active agents: doxorubicin (Dox), mitomycin-C lipidic prodrug (MLP), and alendronate (Ald). Dox and MLP are available in single drug liposomal formulations: pegylated liposomal Dox (PLD, Doxil®), clinically approved, and pegylated liposomal MLP (PL-MLP, Promitil®), in phase 1-2 clinical testing...The Ald-free formulation, PLD-MLP, displayed similar pharmacokinetic properties to PLAD-MLP, but its therapeutic activity was lower. PLAD-MLP is a novel multi-drug liposome formulation with attractive pharmacological properties and powerful antitumor activity and is a promising therapeutic tool for combination cancer chemotherapy."

Journal • Oncology

PROMIFOX: Assessment of Safety and Therapeutic Efficacy of Promitil in Combination With Folfox in Patients With GI Malignancies (clinicaltrials.gov) - P1b | N=12 | Recruiting | Sponsor: Lipomedix Pharmaceuticals Inc. | Trial completion date: Nov 2021 ➔ Nov 2022 | Trial primary completion date: Sep 2021 ➔ Sep 2022

Combination therapy • Trial completion date • Trial primary completion date • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Intravenously Administered Liposomal PROMITIL in Combination With External Beam Radiotherapy in Cancer Patients (clinicaltrials.gov) - P1b; N=18; Completed; Sponsor: Lipomedix Pharmaceuticals Inc.; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion • Oncology • Solid Tumor

Intravenously Administered Liposomal PROMITIL in Combination With External Beam Radiotherapy in Cancer Patients (clinicaltrials.gov) - P1b; N=18; Active, not recruiting; Sponsor: Lipomedix Pharmaceuticals Inc.; Trial completion date: Jun 2021 ➔ Dec 2021; Trial primary completion date: Mar 2021 ➔ Oct 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Simulated gastrointestinal digestion of camel and bovine casein hydrolysates: Identification and characterization of novel anti-diabetic bioactive peptides. (PubMed, Food Chem) - "While LPTGWLM, MFE and GPAHCLL as most active inhibitor of AG and HLPGRG, QNVLPLH and PLMLP were predicted to be active against DPP-IV. Overall, BC and CC hydrolysates can be proposed to be used in different food formulations as functional antidiabetic agents."

Journal • Gastrointestinal Disorder

ForDoz Enters Contract Manufacturing Agreement for Oncology Liposomal Product with LipoMedix (PRNewswire) - "ForDoz Pharma has entered into an agreement with LipoMedix for manufacturing its lead compound, pegylated liposomal Promitil® (PL-MLP) for a Phase 2 clinical study....Promitil's unique liposomal formulation is designed for selective delivery of the therapeutic agent to cancer-affected tissues and is ideally suited for cancer chemoradiotherapy. In studies, it has been shown to be active against a broad variety of cancer types in animal models, including colorectal, gastric, pancreatic and multi-drug resistant tumors."

Licensing / partnership • Preclinical • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

PROMIFOX: Assessment of Safety and Therapeutic Efficacy of Promitil in Combination With Folfox in Patients With GI Malignancies (clinicaltrials.gov) - P1b; N=12; Recruiting; Sponsor: Lipomedix Pharmaceuticals Inc.

Clinical • Combination therapy • New P1 trial • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology

Intravenously Administered Liposomal PROMITIL in Combination With External Beam Radiotherapy in Cancer Patients (clinicaltrials.gov) - P1b; N=18; Active, not recruiting; Sponsor: Lipomedix Pharmaceuticals Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Mar 2021 ➔ Jun 2021; Trial primary completion date: Nov 2020 ➔ Mar 2021

Clinical • Combination therapy • Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Development of Promitil®, a lipidic prodrug of mitomycin c in PEGylated liposomes: From bench to bedside. (PubMed, Adv Drug Deliv Rev) - "This association of pharmacokinetic parameters with patient outcome suggests that arrest of tumor growth is related to the enhanced tumor localization of long-circulating liposomes and highlights the importance of personalized pharmacokinetic evaluation in the clinical use of nanomedicines. Another important area where PL-MLP may have an added value is in chemoradiotherapy, where it has shown a strong radiosensitizing effect in animal models based on a unique mechanism of enhanced prodrug activation and encouraging results in early human testing."

Journal • Review • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Intravenously Administered Liposomal PROMITIL in Combination With External Beam Radiotherapy in Cancer Patients (clinicaltrials.gov) - P1b; N=18; Recruiting; Sponsor: Lipomedix Pharmaceuticals Inc.; Trial completion date: Feb 2020 ➔ Feb 2021; Trial primary completion date: Oct 2019 ➔ Oct 2020

Trial completion date • Trial primary completion date

LipoMedix Announces Publication of Positive Phase 1 Data for Promitil® (PL-MLP) in Research Journal Investigational New Drugs (GlobeNewswire, LipoMedix) - "LipoMedix...today announced that Phase 1 data of Promitil® (PL-MLP) in patients with metastatic colorectal cancer (CRC) was published in the research journal Investigational New Drugs. This study analyzed 53 patients with advanced, treatment-refractory CRC treated with Promitil either as a single agent or in combination with capecitabine and/or bevacizumab."

P1 data

Pharmacokinetics of mitomycin-c lipidic prodrug entrapped in liposomes and clinical correlations in metastatic colorectal cancer patients. (PubMed, Invest New Drugs) - "Methods Plasma levels of MLP were examined in 53 CRC patients, who received PL-MLP either as single agent or in combination with capecitabine and/or bevacizumab. The correlation of neutrophil count and CEA level with pharmacokinetic parameters of MLP is an unexpected finding that needs further investigation. The association of long T½ of MLP with stable disease and longer survival is consistent with an improved probability of disease control resulting from enhanced tumor localization of long-circulating liposomes and underscores the relevance of personalized pharmacokinetic evaluation in the use of nanomedicines."

Clinical • Journal • PK/PD data

LipoMedix announces publication of positive phase 1 data for Promitil (PL-MLP) in research journal Investigational New Drugs (GlobeNewswire, LipoMedix) - P1, N=88; NCT01705002; Sponsor: Lipomedix Pharmaceuticals Inc.; "Promitil was well-tolerated with a good safety profile, as previously reported. Promitil treatment resulted in a substantial rate of disease stabilization, reported in 15 out of 36 efficacy-evaluable patients (42%). Prolonged survival of stable disease patients was also observed, with a median survival of 14.4 months, significantly longer than of progressive disease patients (6.5 months) and non-evaluable patients (2.3 months)."

P1 data