our products

CANCER THERAPEUTICS

Our nanoparticle carrier platform is a hybrid of polymer coating and inorganic nanoparticle core, which takes full advantage of both materials to overcome siRNA delivery barriers such as short blood half-life, poor cellular uptake, and off-target delivery, while minimizing toxicity. Because the siRNA is loaded onto the external surface as the final modification, our nanoparticle carrier has great versatility for siRNA based therapies toward personalized medicine.

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PDX-001 is a targeted nanoparticle for delivery of therapeutic siRNA for treating HER2+ breast cancer. The development is in collaboration with OHSU. It has been funded by a fast-track phase I/II SBIR contract from NIH/NCI as well as angel funds (the Prospect Creek Foundation and Schwab Charitable Trust). HER2 accounts for 20-25% of all breast cancer but the treatment costs account for >50% (or $7.6B in 2013 revenues) of the breast cancer market. HER2+ breast cancer becomes resistant to gold standard HER2 targeted therapies such as Herceptin and Tykerb within a year. We have shown that cancer cells that have acquired resistance to HER2 targeted therapies are still responsive to our siRNA against HER2 (the sequence is highly optimized in house). In addition to siHER2, antibody is also used on our nanoparticles for targeting HER2+ tumors as well as imparting inhibition of the HER2 pathway. See publication.

FIBROSIS TREATMENT

PDX-002 is a topical formulated nanoparticle platform for siRNA delivery to treat skin fibrosis. Funded by an R01 grant from NIH/NIGMS, in collaboration with OHSU, we have developed a nanoparticle platform for dermal delivery of siRNA. In addition to the targeted silencing of a key pro-fibrotic gene, we have shown that the mesoporous silica carrier itself can sequester reactive oxygen species (ROS), which is linked to NOX4 reduction and the reduction of hallmark biomarkers of fibrotic disease (collagen I and α-smooth muscle actin). Collectively, the platform has shown good efficacy in the lowering of skin thickness in a relevant skin fibrosis model. The technology is under pre-clinical studies. See publication.

Nanostructured Oral Chelation Therapy for Mercury, Cadmium, Lead, and Arsenic.

Chelating agents, dimercaptopropane sulfonic acid (DMPS), dimercaptosuccinic acid (DMSA), and ethylenediaminetetraacetic acid (EDTA), were developed many decades ago for treating acute metal poisoning. However, their efficacy is not optimal due to the noted metal rebound observed upon treatment cessation. They also have a propensity to remove essential minerals and thus cannot be used long term for treating chronic exposure due to adverse effects. To address this unmet need, we seek to utilize benign mesoporous silica grafted with thiols (SH-SAMMS, PDX-003) to effectively capture mercury, lead, cadmium, and arsenic in the gastrointestinal tract (GI). Preliminary studies in rats fed with methyl mercury showed that SH-SAMMS given orally could effectively reduce total mercury levels in blood, liver, kidneys, brain, bone, and muscle even after the mercury already absorb to the body. SH-SAMMS also reduced gut absorption of cadmium and lead in rats leading to decreased deposition of cadmium in the liver and lead in blood and bone. SH-SAMMS does not absorb to the body and its high selectivity of the thiol adduct to the heavy metals limits interference with most essential minerals, making it suitable for long term use. See publication.

HYPERPHOSPHATEMIA

PDX-004 is an oral formulation of mesoporous silica modified with iron. The technology development is in collaboration with OHSU and PNNL and has been sponsored by a Small Business Technology Transfer (STTR) grant from NIH/NIDDK as well as commercialization development grant from ONAMI. Hyperphosphatemia is universal to end stage chronic kidney disease patients and a majority of dialysis patients totaling 400,000 in the US and 2 million worldwide. Current oral phosphate binders to treat hyperphosphatemia still have many drawbacks, including a high risk of calcification, high costs ($2100-$6500 per patient a year), low-to-moderate efficacy, gastrointestinal adverse effects, and high pill burdens (500-800 mg tablet, 3-12 tablets a day). These lead to low pill compliance, a major reason why patients fail to manage their hyperphosphatemia, which can be fatal. Although this class of drugs generates ~ 1.4 billion USD a year in revenues, new R&D in search for the better drugs is lacking, lagging behind the state of technology. To address the medical need, PDX Pharmaceuticals is developing a novel oral phosphate binder. Innovation in this project lies in the utilization of our nanotechnology and ligand design expertise to revolutionize oral phosphate binders. Oral formulation of iron functionalized silica has been optimized for phosphate capture and under preclinical studies. See publication.