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Principal Investigator: Katherine Marie Eichinger
Organization: DUO ONCOLOGY INC
Fiscal Year: 2024
Award: $399,970
Funding agency: National Cancer Institute
PROJECT SUMMARY
Annually, pancreatic cancer (PC) has a global incidence of more than 495,000 cases and a mortality rate
of almost 460,000 cases. Most of these patients (~80%) receive late-stage diagnoses when their tumors
cannot be surgically resected, necessitating pharmacotherapy. A majority of PC patients (81%) have
dense, fibrous stroma tissue surrounding their tumors, which is a negative prognostic. Despite treatment,
PC has the lowest 5-year survival rate of all cancers.
Nanomedicines have been developed for use in oncology to reduce toxicity and improve efficacy. Indeed,
drugs like protein-bound paclitaxel nanomedicine (Nab-PTX, Abraxane) and liposomal irinotecan (Nal-
IRI, Onivyde) have led to dramatic improvements in response rates for cancers such as breast, lun g, and
leukemia. However, nanomedicines’ efficacy gains in PC have fallen far short of those seen in other
indications. This stems in part from PC’s stromal tissue that blocks the extravasation and penetration of
large nanomedicines like Nab-PTX and Nal-IRI (> 100nm).
To overcome the delivery challenges of existing nanomedicines, Duo Oncology is developing DUO-
207, an ultrasmall nanoparticle (< 30 nm) comprised of a copolymer-conjugated gemcitabine
(PGEM) that encapsulates paclitaxel (PTX). DUO-207’s fixed dose combination delivers the active
moieties in GEM and Nab-PTX, a current standard of care (SoC) for advanced PC. DUO-207 contains four
innovations that address gaps in this SoC therapy to optimize safety, efficacy, and convenience. 1) The
patent-pending polymer chemistry behind PGEM protects GEM from rapid inactivation via cytidine
deaminase in the blood and liver. Clinically, large doses of GEM are administered to compensate for rapid
inactivation and increase the drug’s bioavailability to tumor tissue but this approach contributes to dose
limiting toxicity. 2) In DUO-207, GEM is conjugated to the polymer, facilitating its controlled gradual
release and providing prolonged exposure to GEM, which has been associated with improved clinical
efficacy. 3) The bonds that link GEM to the polymer are sensitive to three conditions common to the tumor
microenvironment, thereby aiding the release of GEM adjacent to cancer cells. 4) Lastly, our novel
polymer chemistry allows for the self-assembly of 14nm PGEM micelles that can accommodate high drug
loading of PTX in a single i.v. infusion. DUO-207’s ultrasmall size allows for its effective penetration of and
accumulation in tumor tissue as demonstrated in our preclinical orthotopic model of PC using genetically
engineered Kras-Pdx1-Cre (KPC) cells that produce dense stroma.
In this application we propose to perform murine toxicology and tumor growth studies to build a safety and
efficacy profile for DUO-207 compared to current Soc. Ultimately, the innovations of DUO-207 will improve
survival outcomes, the toxicity profile, and quality of life for patients suffering from advanced PC.
Terms: <Abraxane><Address><Advanced Development><Anzatax><Asotax><Binding Proteins><Bioavailability><Biochemistry><Biological Availability><Biological Chemistry><Biological Markers><Blood><Blood Reticuloendothelial System><Blood Serum><Body Tissues><Breast><Bristaxol><C57BL/6 Mouse><Campto><Cancer Treatment><Cancers><Canine Species><Canis familiaris><Cell Body><Cells><Clinical><Compensation><Complete Blood Count><Cytidine Aminohydrolase><Cytidine Deaminase><Data><Death Rate><Development Plans><Diagnosis><Difluorodeoxycytidine><Dogs><Dogs Mammals><Dose><Dose Limiting><Drug Therapy><Drugs><Encapsulated><European><Exposure to><Extravasation><Feedback><Genetic Engineering><Genetic Engineering Biotechnology><Genetic Engineering Molecular Biology><Goals><Grant><Hematology><IV Infusion><Incidence><Intravenous infusion procedures><Leakage><Legal patent><Ligand Binding Protein><Ligand Binding Protein Gene><Link><Liposomal><Liposomes><Liver><Lung><Lung Respiratory System><Malignant Cell><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Pancreatic Neoplasm><Malignant Tumor><Malignant neoplasm of pancreas><Maximal Tolerated Dose><Maximally Tolerated Dose><Maximum Tolerated Dose><Medical><Medication><Medicine><Mice><Mice Mammals><Micelles><Modeling><Monitor><Murine><Mus><Nephrotoxic><Oncology><Oncology Cancer><Operative Procedures><Operative Surgical Procedures><Organ><Orphan Drugs><Outcome><Paclitaxel><Paclitaxel (Taxol)><Pancreas Cancer><Pancreas Neoplasms><Pancreas Tumor><Pancreatic Cancer><Pancreatic Tumor><Patents><Pathology><Patients><Penetration><Pharmaceutical Preparations><Pharmacotherapy><Phase><Phase I Study><Physiologic Availability><Polymer Chemistry><Polymers><Praxel><Protein Binding><QOL><Quality of life><Randomized><Recombinant DNA Technology><Regimen><Regulatory Pathway><Resected><Safety><Saline><Saline Solution><Serum><Solid Neoplasm><Solid Tumor><Spillage><Surgical><Surgical Interventions><Surgical Procedure><Survival Rate><Tail of pancreas><Taxol><Taxol A><Taxol Konzentrat><Testing><Therapeutic><Time><Tissues><Toxic effect><Toxicities><Toxicokinetics><Toxicology><Treatment outcome><Tumor Tissue><Tumor Weights><Work><advanced pancreatic cancer><anti-cancer therapy><bio-markers><biologic marker><biomarker><bound protein><camptosar><cancer cell><cancer microenvironment><cancer therapy><cancer type><cancer-directed therapy><canine><clinical efficacy><copolymer><dFdC><dFdCyd><determine efficacy><domestic dog><drug treatment><drug/agent><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><efficacy study><evaluate efficacy><examine efficacy><falls><gemcitabine><genetically engineered><hepatic body system><hepatic organ system><improved><innovate><innovation><innovative><intravenous infusion><irinotecan><kidney toxicity><leukemia><malignancy><mortality rate><mortality ratio><mouse model><murine model><nano medicinal><nano medicine><nano particle><nano-sized particle><nanomedicinal><nanomedicine><nanoparticle><nanosized particle><neoplasm/cancer><nephrotoxicity><novel><pancreatic cancer model><pancreatic cancer patients><pancreatic malignancy><pancreatic neoplasia><pancreatic neoplasm><pancreatic tumor model><particle><patients with pancreatic cancer><phase 1 study><polymer><polymeric><pre-clinical><pre-clinical study><preclinical><preclinical study><prognostic><prospective><pulmonary><randomisation><randomization><randomly assigned><response><self assembly><sex><standard of care><stem><surgery><survival outcome><tumor><tumor growth><tumor microenvironment><ultrasound>