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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - SMARTRIOX (Disruptive targeted drug delivery system via synergistic combination of intelligent DNA molecular machines and gated mesoporous nanoparticles)

Teaser

Summary

\"By the year 2019, thousands of APIs (Active Pharmaceutical Ingredients) were developed and approved to treat different diseases, yet not even one efficient technology was approved to deliver these different API precisely to their target tissues! Developing a targeted delivery platform will benefit these APIs by improving their efficacy and reducing their toxicity. It will broaden their treatable indications, improve their results and allow them renewed patent rights. \"\"Traditionalâ€ delivery methods, such as Injections or tablets deliver only a small percentage of their original doses to the tissues requiring treatment, and instead, most of the dose arrives to healthy tissue causing severe toxicity. Current Drug Delivery Platforms (DDPs) such as liposomes or polymers face the same efficiency problem, not offering the possibility to target specific body tissues affected by a disease. On the other hand, Targeted Therapies such as monoclonal antibodies, target only an affected protein, but are costly and generally amenable to a small proportion of patients bearing the specific protein for which the treatment is directed. Efforts to develop Targeted Drug Delivery Platforms (T-DDPs) that overcome these limitations resulted in little success to date, creating a substantial unmet need. An ideal T-DDP should be programmable, allow flexibility and decrease development costs. It should enable different targeting mechanisms, be loaded with various APIs, improve the API\'s pharmacokinetics, pharmacodynamic profile and address an array of indications applicable to the majority of patients.
There is an urgent unmet need within the pharma/ biotech industry for development of more efficient T-DDP. Computers and machines had drastically altered our lives changing many aspects of our reality. However, our ability to deploy even mini computers that will interface directly with biology at the cellular and molecular levels is limited. Currently this interaction with biological processes within the organism using drugs is very limited. Fresh thinking and breakthrough leaps are required in the way we imagine, design and execute novel drug delivery platforms.
The ideal drug delivery platform should fulfill the following criteria: (i) High treatment efficacy; (ii) precise targeted delivery; (iii) minimal toxicity and side effects; (vi) significant reduction of the required dose; (v) controlled bio-distribution and biokinetic (vi) the ability to address as many different indications as possible. (vii) the ability to have multiple variable dependent targeting to avoid the creation of resistance through down/up regulation or natural selection such as the case in cancers. (viii) have the ability to target different cells expressing different variables in the same disease such as the case in primary and metastatic tumors.
The logical way to design such delivery platforms is to rely on a programmable / customizable technology incorporating components that can be found in living organisms and providing the possibility to be programmed to perform the following tasks described above.
THE SOLUTION: S.M.A.R.T, a Stimuli Multi Adjusted Responsive nano Technology platform which combines two cutting edge research fields (Patents already approved in EU and US):
1. Biocompatible porous nanoparticles, used as drug carriers to encapsulate the selected Active Pharmaceutical Ingredient (API) to treat the disease of interest. Each type of nanoparticle has different unique chemical properties, and so in each case, is selected based on the type of the API to be loaded into it.
2. DNA molecular sensors, machinery and Biocomputing: This scientific field is relatively novel showing great prospects and advances in the last few years. Our nanoscale DNA-based computerized machines follow a sequence of preprogrammed algorithms conceived to sense a combination of variables in their environment to thereafter unload their active payloads. The DNA component is the stimuli-responsiv\"

Work performed

During the first period of the project we were able to cutomize the manufacturing procedure of TXN770 from university lab to commercial standards. We incoroporate the use of commercialy available high standard reproducible meosporous silica nanoparticles. Additionally we were able to optimize many aspects of the manufacturing process. We were also able to advance in the regulatory pathway preparing the orphan drug designation request for TXN770

Final results

Until the end of the project we are expecting to be able to manufacture TXN770 in cooperation with a contract manufacturer in larger batch quantities and have first clinical results in TNBC patients. In case our results prove safety and better efficacy a substantial step will be made to improve the outcome of TNBC patients and proof the potential of the S.M.A.R.T platform in many other oncologic and non oncologic indications.