Accurin

Accurin is a nanomedicine of which there are many specific targeted nanoparticles that deliver different medications and target different receptors. Nanomedicine is a field of drug delivery that hopes to use nanotechnology, such as nanoparticles, in medical treatment. Nanoparticles used in this manner typically have specific properties and range from 1-100 nm in diameter. Nanoparticles such as Accurin are used in specifying drug delivery to certain cells. Nanoparticles are also usually associated with lower side effects and lower drug consumption. Accurins were developed with the intention of specific targeting of tumor cells and offer a possible future treatment of cancers with a safer and more effective method of treatment.
Accurins include:
* BIND-014, targeting PSMA delivering docetaxel, in phase 2 clinical trials
* BIND-510, targeting PSMA delivering vincristine. IND soon.
* BIND-2206 containing the AKT inhibitor MK-2206.
Workflow
Accurins are made up of four layers that contribute to their therapeutic function. The first layer is a controlled-release polymer matrix. This layer ensures that the therapeutic agent of choice is released at the site of diseased tissue. The second layer incorporates polyethylene glycol onto polylactic acid in nanoparticles in order to supply a conjugation location for the chemotherapeutic agent of choice. Third, another layer of just polyethylene glycol is used to prevent the immune system from recognizing the molecule and therefore prevents immune clearance of the treatment allowing for a greater circulation in the system.
In 2013, Bind Therapeutics announced an official collaboration with Pfizer, a pharmaceutical industry company. The aim of the collaboration was to commercialize Accurins. The agreement stipulated that Pfizer would have the exclusive ability to commercialize their choice of Accurins. The companies agreed to collaborate on preclinical research, though Pfizer maintained responsibility for development and commercialization responsibilities. In 2016 Bind Therapeutics declared bankruptcy and was officially acquired in full by Pfizer.
Clinical trials exemplified BIND-014’s tumor shrinking abilities. The nanoparticle was even able to shrink tumors that were otherwise resistant to docetaxel. In comparison to free drug dosage, BIND-014 has proven to be up to ten times more effective at docetaxel delivery. For this increase in efficacy there is no associated toxicity increase. In direct comparison to Taxotere, a popular intravenous docetaxel treatment, BIND-014 is a more effective treatment method.
Though similar docetaxel treatments are associated with defects in the cardiovascular system, BIND-014 was free from association with any cardiac abnormalities. Side effects that were observed include: fatigue, nausea, and diarrhea. Other than the listed side effects, patients were found to exhibit tolerance for BIND-014 treatment with minimal safety concerns.
BIND-510
BIND-510 was an Accurin developed with the investigated application of treating prostate cancer. Similar to BIND-014, the nanoparticle’s target was prostate-specific membrane antigen (PSMA), though the Accurins differ in the delivered drug which was vincristine for BIND-510. Vincristine is a chemotherapy drug used to treat a variety of cancers and has an anti-mitotic function, meaning it prevents cancer cells from dividing and therefore stops cancer growth.
Clinical trials evaluating BIND-510 supported its efficacy in comparison to free drug vincristine. In comparison to free dosage, BIND-510 was eight times more effective. Additionally, BIND-510 was associated with a decreased clearance, longer delay in tumor growth, a greater tolerability, and increased anti tumor behavior.
BIND-2206
BIND-2206 was another Accurin developed for the purpose of treating various cancer lines. Unlike previous Accurins, BIND-2206 targets the protein kinase AKT. Additionally, BIND-2206 delivered primarily MK-2206 and possibly AZD2811. AKT was targeted as it is one of the most active protein kinases in most cancers. Overactivation of AKT is associated with uncontrollable cell growth. Unlike BIND-014 and BIND-510, BIND-2206 delivers drugs that have yet to be used in commonplace for cancer treatment.
MK-2206 and AZD2811 are AKT inhibitors that have yet to be approved for patient use. AKT, also known as protein kinase B, is an aurora kinase whose overexpression is strongly related to drug-resistant cancers that often have poor prognosis. The drugs MK-2206 and AZD2811 function by inhibiting AKT signaling. However, free drug dosage of MK-2206 and AZD2811 appear to have high toxicity as mice trials involving the drugs resulted in death after three treatments. Therefore, since Accurins have previously demonstrated an ability to target agents with a reduced toxicity as compared to free drug dosage, BIND-2206 was hypothesized to reduce toxicity levels and increase the possible usage of AKT inhibitors as viable cancer treatments.
Other Applications
As a targeted therapy, Accurin holds great prospects for the personalized cancer treatment’s future. Additionally, there lies a possibility for utilizing Accurins for treatments beyond cancer.
Personalized Medicine
Nanoparticle medicine enhances the possibilities for personalization as it allows for individualized prediction, treatment, and prevention of disease and disorder. As a nanoparticle treatment Accurins are no exception to this and are significant for the personalization of cancer treatment. Since the target and drug can be changed in Accurins the treatment can be personalized depending on the severity of the patient’s cancer and the type of cancer the patient suffers. Furthermore, it was discovered that certain patients may benefit more from Accurin treatment depending on their expression of the target molecule. For BIND-014 patients who expressed more PSMA experienced more benefits from treatment. This implies that analysis of patients’ expression of the target in disease would be a possible screening process for prediction of treatment efficacy. As a patient’s disease progresses biological profiling may be used to keep track of developments that may evaluate a patient’s response to Accurins.
Advantages and Limitations
Though Accurin treatments have many associated advantages related to their safety profiles and reduced toxicity of the delivered drug, no Accurins were ever made commercially available due to limitations in efficacy.
Advantages
As mentioned, Accurin treatment is advantageous due to the associated lowered risk with toxicity and drug clearance. Since Accurin uses an encapsulation technique, toxicity is reduced and slow-releasing Accurins especially are highly associated with better safety profiles. Furthermore, Accurins are able to avoid clearance from the immune system which allows for longer systemic circulation of the drug and thus an increased treatment efficacy.
Limitations
There are associated limitations to Accurin usage that may possibly explain why Accurin therapeutics were never actually commercialized. While Accurin therapeutics demonstrated high efficacy rates in early studies, as the treatment progressed to Phase III clinical trials the success rate was measured at only 14%.

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