Entrepreneurship | Tec-Monterrey

Overview

It is estimated that by 2050 antibiotic resistance will cause around 10 million deaths per year, being one of the 10 main public health threats [1]. This resistance has developed due to unnecessary prescription, self-medication and incomplete treatment [2].

Pseudomonas aeruginosa is one of the most frequently isolated microorganisms in critically ill patients. It is a causal agent of infections with high rates of morbidity and mortality [3], among which nosocomial pneumonia stands out. Its eradication has been complicated over time due to its remarkable ability to resist antimicrobial agents, which is due in part to the excessive use of antibiotics during treatment. P. aeruginosa is resistant to antibiotics in a percentage of 80 to 92% for amikacin, piperacillin/tazobactam, cefepime, ceftazidime, meropenem, and ciprofloxacin.

rnAIR is an entrepreneurship interested in becoming a startup focused on a gene silencing system delivered through modified M13 bacteriophages that are nebulized and stabilized by microfludically produced liposome-phage complexes. Our gene silencing is based on computationally optimized sRNAs evaluated through Machine Learning protocols.

Mission & Vision

Mission

Our mission is to develop an integrated, new and accessible nebulizer with a gene silencing system delivered through liposome-phage complex capable of overcoming antibiotic-resistant bacteria risks on respiratory system tissues, with the use of a self-created small RNAs bioinformatic software, that can be used by all scientists and hospitals.

Vision

Our vision is to become leaders in the development of a new nebulizer system for silencing antibiotic resistant genes and early pioneers of a small RNAs bioinformatic software. Seeking to decrease antibiotic resistance of Pseudomonas aeruginosa with the use of synthetic biology.

Meeting with Dr. Raúl Villarreal Lara

We had a talk with the director of the biotechnology engineering program at Tec de monterrey and he told us how to create a business model canvas, which is used in the entrepreneurship area to help us visualize our problem, solution, key partners, channels, cost structure and beneficiaries. Also, he helped us conclude that our most important customer is the one to whom we are going to sell our product. In this case, it would be the hospitals that have specialized personnel for the correct use of the nebulizer.

Similarly, he explained to us that there were different types of value propositions and that we should focus on what we can contribute to society or to hospitals. rnAIR seeks to reduce the amount of money spent on broad-spectrum antibiotics and improve accessibility to the population. In this way, with our project we have a cheap, economical and safe treatment for antibiotic resistance. Accessible to all hospitals and communities.

Meeting with Eduardo Mijael Linares Barbosa

The meeting with Dr. Eduardo Mijael Linares Bardosa was very useful for us, we mainly addressed the issue of regulation and patent procedures in our country. He guides us with the procedure to carry out procedures before the IMPI (Mexican Institute of Intellectual Property), from the format required for the documents delivered to the process of granting patents and conservation of rights, as well as expiration and rehabilitation. from the same. In addition, we identify the correct process to be sure according to the type of patent we wish to register, along with sample applications that must be filled out to begin registration.

Product

To transform our diagnostic methodology to a product that can be used by a health care physician, our modeling team designed a nebulizer device with the use of the program SolidWorks. The system is integrated by a modified M13 bacteriophages stabilized by microfludically produced liposome-phage complexes. This is due to the fact that sRNAs prevent the translation of protein mRNAs that confer antimicrobial resistance to Pseudomonas bacteria. Bacteriophages are encapsulated in liposomes suministred to the lungs by a vibrating mesh nebulizer. The next images are a modulation of the nebulizer proposed by our team:

Competitor analysis

Our product is a solution that meets all the needs in the silencing process, from the design to the delivery of phages to the lungs, compared to other strategies targeting Antimicrobial-Resistant enzymes.

Among the advantages of this phage encapsulation and delivery system are efficiency, reduction in delivery time, retention at the desired target within the lung, and biocompatibility with the human body [7]. Optimization in the sRNA design was performed with the help of software developed by the team, which can be adapted to be used for other antibiotic-resistant bacteria.

We designed a product aimed at hospitals and private clinics that will use rnAIR to treat their own patients.

SWOT Analysis

We applied the SWOT analysis tool to strategically plan the best viability of our project, so in the future we can stay ahead of the market trends. In addition, we analyzed the internal initiatives, both those that work well and those that do not, from this we considered the possible results of the strengths and weaknesses presented, and finally, we took into account the areas that have the potential to cause problems that are outside of our control.

Figure 3. Swot Analysis of rnAIR project.

Clinical Trial Phase

We based our clinical trial on the Human Research Protocols indicated by the Mexican Federal Commission for the Protection against Health Risks (Comisión Federal para la Protección contra Riesgos Sanitarios). [8] The blue boxes represent user inputs, while the green boxes represent "if's" which help us to predict actions that the user may perform in the future.

Figure 4. Human Research Protocols indicated by the Mexican Federal Commission for the Protection against Health Risks (Comisión Federal para la Protección contra Riesgos Sanitarios)[8].

The blue boxes represent user inputs, while the green boxes represent "if's" which help us to predict actions that the user may perform in the future.

Patents

A patent is an exclusive right granted by a state to a holder to protect their invention. This can be a product or a result development process, in any technical area. The patent grants the owner of this product the exclusive right to prevent others from exploiting his invention, all within a limited period. In other words, the patent owner can prevent third parties from manufacturing, using, marketing, and importing the patented product if they do not have legal authorization. This is a way of materializing the creations or inventions of the intellect, in such a way that it becomes an asset.

At the Mexican Institute of Industrial Property (IMPI), you can carry out the administrative procedures to obtain the granting of a patent, a trademark registration, or a request for bibliographic or technical searches of patent documents. However, obtaining a patent in Mexico is a fairly long process, therefore it leads to monetary expenses [8].

We accomplished a patent search to find similar products and ensured that our product is patentable. The "Espacenet" and “Google Patents” search engines were used to search for existing patents using keywords including: “liposomes drug delivery”, “nebulizer delivery”, “liposome-phage”, “drug delivery”.

During our research 5 similar patents were discovered:

The first patent we found was “Superloaded Liposomes for Drug Delivery (WO2005115337A1)” it conveys a liposome in which at least a portion of the desired drug molecule contains a functional group reactive with another functional group present in at least one lipid fraction, the drug is covalently bound to a membrane lipid through a chemical bond [9].

The following patent we discovered was “Nebulized liposomes for the pulmonary application of drug compounds (US8652512B2)” which consists of a method to elaborate specific liposomal formulations for pulmonary applications of therapeutic substances. It combines liposomal components, DPPC, and cholesterol with non-toxic excipients, sphingomyelin, dimyristoyl phosphatidylcholine, and/or polyethylene glycol, in order to develop liposomes that have stable characteristics during nebulization with commercially obtainable nebulizers and present sustained discharge kinetics of encapsulated drug substances [10].

The third identified patent “Drug Delivery Stent with Extended in Vivo Drugs Release (CA2641662A1)” consists of a technique for diminishing the rate of restenosis. It implicates constant delivery of an anti-restenosis agent such as paclitaxel from the stent to the vascular tissue needing treatment in a supervised and maintained drug release [11].

Subsequently we discovered “Method for Producing a Drug Delivery System on the Basis of Polyelectrolyte Complexes (WO2011121019A2)” it assembles a drug delivery system which releases medicaments in a locally targeted and controlled manner. The objective is achieved by a mechanism in which polyanions and polycations are mixed, based on the charge monomer units, in which medicaments are added before, after or during the mixing of the polyelectrolytes. After the mix the resulting polyelectrolyte complex is adapted to the surface of a medical agent or directly at the released site of the medicament [12].

The next patent we recognize “Iontophoresis, Electroporation and Combination Patches for Local Drug Delivery (CA2645935A1)” is a patch-based device which increases the local delivery of plasmids, pharmaceuticals, genes, drugs, and other agents into the tissues. It supplies an electrical driving force that can accelerate the migration of drugs and other therapeutic agents from a polymer into body tissues and cells via iontophoresis, electroporation or a combination of the two [13].

Our Potential Patent

To boost our product, we seek to patent the system developed on the encapsulation of liposomes, according to the research carried out on patents with the mechanism used in our project, it has not been registered, which demonstrates that the technology developed is innovative. In this way, we seek to protect our developed system, for this, we must comply with the corresponding process that consists of the correct filling of the application form, followed by the payment of the corresponding fee, then we would continue with presenting the description, claims, and other information required. To establish the document that supports our work, as well as the necessary technical drawings and thereby specify the invention, in turn, we must take into account making a list of sequences or any other biological material that we make use of. We will carry out this process before the IMPI (Mexican Institute of Industrial Property / Instituto Mexicano de la Propiedad Industrial) to scale our product.

Timeline

We have created a 10 year plan that we would need to follow in order to conclude the project. The time frame explained is very optimistic because it doesn´t include minor setbacks or additional information. The main actions will be: literature research, modeling, finding investors, optimization of sRNA software, development of liposome-phage complex, development of vibrating mesh nebulizer, in vitro studies and clinical trials.

In this project, we have made a literature research of antibiotic resistance in Mexico's health system, the software sRNA designer, the adequate laboratory protocols, among others. Also, we collaborated in the modeling of a software and we did some in vitro studies. So, rnAIR is moving forward according to the following Gantt chart. The next steps will be to finish the in vitro studies, animal trials and human trials.

Figure 5. Gantt Chart representing the timeline of the project rnAIR.

TRL

We applied the methodology of the Technology Readiness Levels with the purpose to identify our level of development to plan and strategy to scale up til make it tradable. We analyzed that we are in the TRL 3, due to we have already done complete research on the technical approach, after that, we received feedback from experts in many aspects of our project, such as the scientific validation as the human approach we estimated, at the same time considering inclusivity and entrepreneurship in our project, then we started with the first experiments at the laboratory and the construction of a prototype, but we still in improving the design and optimizing the process and material employed.

Figure 6. Diagram of the Technology Readiness Level (TRL).

Business Model

We have developed a Business to Business model that puts the hospitals at the center. Mexico’s hospitals are our main client and through them it is planned to reach patients with infections caused by bacteria that are resistant to antibiotics. We have contacted various pharmaceutical companies, doctors and hospitals with whom have highlighted the relevance that rnAIR will have in the future of the Mexican health care system. Likewise, we are validating our proposal with researchers and national companies. We have designed an integrated system capable of overcoming antibiotic-resistant bacteria risks on respiratory system tissues. We have designed a software of small RNAs to validate our proposal.

Total Cost of Research

A cost estimate of the product was made by analyzing the quality of each of the pieces to obtain an efficient construction of the product while maintaining a reduction in costs to obtain an accessible price for the final consumer.

According to our estimation, considering the laboratory test, liposome encapsulation and nebulizer development, the total cost of research is approximately $7,607.90 (USD) [14-16].

Table 1.2 Total cost of laboratory tests.

Table 2. Total cost of liposome encapsulation..

Table 3. Total cost of nebulizer development.

Potential Market

The global burden of deaths from antibiotic resistance could balloon to 10 million lives each year by 2050, at a cumulative global economic output cost of $100 trillion USD [17]. At the same time, according to the World Health Organization, at least 700,000 people die yearly due to drug-resistant diseases, including 230,000 people who die from multidrug-resistant tuberculosis [1].

Figure 8. Global Antimicrobial Resistance Market, according to the report “Global Antimicrobial Resistance Market Size, Trends & Growth Opportunity, By Disease, By Pathogen, By Drug Class By Region and Forecast till 2027”

Various reports state that if no action is taken, the global domestic product loss from 2015 to 2050 would be 7%, or $250 trillion USD. It is also stated that the global deaths would increase up to 10 million per year if no hard countermeasure is applied [18]. Figure 8 demonstrates the research market of antimicrobial medicine, which highlights an increasing necessity and opportunity.

Future Partners

Secretaría de Salud: The Secretary of Health is the government department focused on managing the Mexican health system [19].

COFEPRIS: Federal Committee for Protection from Sanitary Risks (Comisión Federal para la Protección contra Riesgos Sanitarios) is the department that is responsible for regulating medical devices and the importation requirements in Mexico [20].

WHO: The World Health Organization is the agency responsible for international public health. On May 15, 2015 WHO approved a new global plan on antibiotic resistance [21].

FDA: The United States Food and Drug Administration is known as the federal agency that regulates all medication and devices of the human health services [22].

What can we gain from our partners?

Requirements for clinical trials

Connections with the organizations, public and private sector

Legal documentation for distribution

Legal documents for appropriate medical devices, health regulations

Funding

Support with the clinical trials

Crowdfunding

A majority of our funding will come from:

CONACYT Mexico

Tec de Monterrey

FEMSA Grand

Global Affairs in Mexico

Future grand applications

Sponsorships from our partners

rnAIR will seek sponsors to fund the project to continue the research and clinical protocols. However we believe that crowdfunding would be necessary. According to objective number 3 of The Sustainable Development Goals of the United Nations, by 2030 aims to guarantee a healthy life and promote well-being at all ages [23].

An internet page will be created with information on the project and it will be emphasized that the main beneficiaries will be the Mexican communities and the public health sector of Mexico known as IMSS. This is due to the fact that since 2019, Mexico has been in a shortage of medicines. This is because the new President Andrés Manuel López Obrador eliminated some contracts with key pharmaceutical companies. The shortages are of cancer drugs, metformin, insulin, and non-COVID-19 vaccines, among other antibiotics [24].

“...the Mexican Social Security Institute...was unable to fill about 2% of prescriptions in 2019. This value arose to 8% of prescriptions in 2020 [24].”

This has caused in the Mexican community a problem of drug shortages and great human losses. In the future we hope to help all the people of the world, but especially mexicans that aren't able to purchase high cost antibiotics.

Incubation Process & Activities

Throughout these months, we have enrolled ourselves in several Entrepreneurship activities and contests with the objective of developing skills and building a network which will enable us to make our project profitable. As part of these activities we have enrolled ourselves in entrepreneurship conferences and contests, obtaining promising results:

Healthaton

Healthathon 2022 is a hackathon organized by Tec Salud. It is designed for health projects that aims to stimulate entrepreneurship in the field of health and promote young professional talent in Mexico, committed to innovations in the area of health. Which included mentoring sessions, conferences and workshops, and networking, where we got tools to validate our idea and prepare projections to go to market. On the final day of the competition we made a presentation of the highlights of our project. We can gladly announce that this year, we won second place at Healthaton 2022.

Congreso Internacional del Centro de Biotecnología FEMSA

Figure 11. XV Anniversary Biotechnology Congress FEMSA

FEMSA Congress is an initiative created by Tec de Monterrey that seeks to promote and connect Biotechnology companies with the students at Tec de Monterrey. Also, it aims to gather all the scientists and get to know more about the work of researchers of FEMSA Tec de Monterrey. Each year it holds a congress where key actors from the biotechnology industry are brought together. Within the activities, there is the Poster competition: a poster contest supported by FEMSA, where bio students and phd candidates present their work and latest research. Our team participated in the research made by the model and software team, with the presentation of an abstract and a poster of our work, in addition to the presentation and pitch for the judges conformed by specialized scientists.

INCmty

Our remarkable participation in Healthaton, mentioned previously, made us winners of a grant to present our project at the entrepreneurship festival INC Mty with the purpose to obtain continuous improvement in our project. Which we will attend in November of the present year.

INCmty is a platform that since 2013 promotes and connects those who undertake with organizations, companies and investors through varied content that ranges from forums, activations for entrepreneurs, investors, researchers, corporations, families, companies and the community in general, thus building value for Mexico and the world. INCMty organizes an annual festival, with several activities, such as entrepreneurship contests and conferences [3].

What 's next?

Our short and medium term goals (within 5 years from now):
Characterize by RT-qPCR the expression of resistance genes as well as our sRNAs.
Make a comparison between more sRNAs in order to verify the relevance of the scores proposed.
Cytotoxicity assays in macrophages in order to establish the safeness of the M13 nano formulation.
Test the bacteriophages availability to infect once encapsulated in liposomes and nebulized.
Test the safety of our formulation in vivo and availability of the bioaccessibility of our formulation in lungs.
Start a crowdfunding page and keep looking for sponsors.

References

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