Table of Contents
“Do your parents have Diabetes?”
“No… But my grandparents do, both of them and…”
“Ahhh! My grandma also does.”
“……”
It was the impending aging society across the world as a major demographic shift trend that evoked us Sugar Fox group to focus on this topic. Consequently, the experimental team devoting to find the protein that can prevent the combination between the targeted FoxO1 and the its IRE transcription factor which would otherwise promote gluconeogenesis, the excess production of sugar. The fortunately successful experimental trail facilitated the work of business group in Sugar Fox team.
Experimental engineering concept
According to published research, we found that Forkhead box protein O1 (FoxO1) plays an important role in initiating the transcription of enzymes G6Pace and PEPCK. Thus, we intend to reduce the expression of the two enzymes by regulating the expression of FoxO1.
Function test results To regulate the expression of hFoxO1, we will use small molecular compounds from the database to examine their effects on gluconeogenesis. Compound 355 with inhibitory activity of FoxO1 transcriptional activation will be screened by reporter gene assay as the test result shown above.
During the experiments, we strictly followed the laboratory safety measures and comply with the iGEM safety regulations throughout the whole project. The main microorganism we used in the laboratory was the HepG2 cell. The cell lines we make will operate in a laboratory environment and follow the rules of laboratory waste disposal. The discarded engineering strains will be sterilized at 121 Celsius and 20 minutes before being thrown away as medical waste. Therefore. our cells will not spread in the natural environment.
Figure 1. Prototype of our product Dia-355
Our product name is Dia-355, for Dia representing diabetes, and 355 is a compound within the product.
We planned to make our medicine into the tablet form for its advantageous nature in preserving and transporting.
The key enzyme to glucose metabolism are G6Pase PEPCK1 and PC. Signal pathway.
When glucocorticoid went across the cytosol , been recognized by Glucose Receptor(GR). Then binding to more GRE gene, promoting HNF1arerfa binding to IRS. PGC1arerfa could be recruited and interacted with FoxO, binding to activated domain. HNF3 complex followed the other Transcription Factors, binding to their own domain. While being activated, the promoter of G6Pase could be activated.
The model of PEPCK and PC could be similar to G6Pase.
The significance is the Pathway to AKT. While phosphorylation occurred in AKT， has been activated by insulin. Then contacting with FoxO, phosphorylation occurred. It could be expelled from the nuclear. The gluconeogenesis could be inhibited.
Because of lack of insulin, we designed a compound 355 to activate the AKT. While medievaling， the Downstream gene expression was inhibited. Eventually, the pathway of gluconeogenesis was blocked.
We accomplished the cell experiment totally in order to screen the compound that we desired and detective the value of IC50. Conclusion We found that the 355 could prompt phosphorylation of FoxO effectively, inhibit the process of gluconeogenesis and reduce the concentration of sugar in the blood, thereby alleviating the symptoms of type 2 diabetes patients.
We will make our tablet into a canary yellow color to avoid possible psychological rejection of the patients when they take it.
There are 30 pills of tablets, and each 15 pills are placed in one piece of package.
Our tablets are placed in a light blue color box, where there are our group and product name, logo, number of piles, date of manufacture, quality guarantee period, usage, etc.
Portability is one of our top strengths. The net weight of one piece of package of tablets will be set not more than 40mg and it takes up only a small space, so that it is easy to carry with.
The function and effect of our product could last for a long time, therefore the patients only need to take the medicine once for 2 days.
The medicine might only be preserved for 1 month if once it is opened, and it should be kept in a dry place where the surrounding temperature should be no more than 20 degree Celsius due to chemical preservation concerns.
In order to examine our product and the way how we communicate our products’ benefits to specific customer segments, here we use STP analysis to have a better understanding of the market and consumer where STP stands for Segmenting, Targeting and Positioning.
Figure 2. STP map of our product
For segmenting, we segregate our customers into a specific group with various characteristics: our customers are diabetes patients and family members clustered within the age range 40 to 60 years old1 living in the middle and high-income countries’ urban areas. They value effectiveness and convenience more than affordability when they choose to buy a medicine with long-term and frequent use, and they’re experimenting and have a strong awareness of protection.
For targeting, our market size will have an estimated 500 million patients with diabetes in 20302 , Among these, the most profitable customer group is patients and family members of working age or over 65-year-old. Also, this kind of customer group has relatively low customer acquisition costs (CACs) and takes the initiative to contact.
For positioning, our product is dose-dependent and can effectively prevent the blood sugar from increasing and improve glucose tolerance simultaneously, To some extent, it will boost customers’ sense of security and provoke their self-motivation.
PESTLE Analysis for external environment’s evaluation as following:
Our project can easily obtain sufficient capital support through official channels, because the Chinese government is prone to invest in original medical exploration projects. The government is also giving the pharmaceutical companies like us to earn better profit under the condition that the average healthcare spending of the families is increasing.
Currently, the antidiabetic drug industry in China is dominated by oral hypoglycemic medications (for type 2 diabetes). In such a social environment, oral drugs have become the mainstream drugs in the society, so our products are in line with the mainstream of society and have great development space.
Additionally, it is definitely a great opportunity for our product to take over a big part of market share in a situation that the market of innovative drugs with little side effects which requires high technological support is still a vacant field with plenty of room for development.
At the same time, due to the expected market scope of our products, that is, not only the domestic market, but also the foreign market, we need to consider the drug-related regulatory documents promulgated by both of the foreign governments and the domestic governments. Regarding national laws and regulations, we clearly know the relevant usage specifications and have experts to provide more detailed technical guidance, so it’s our realistic aim to make sure the products will not be violating any term.
Finally, considering the above favorable and neutral conditions, and because the economy of scientific research and medicine is still developing rapidly, our analysis reaches at a positive conclusion that our products have a lot of room for development and success factors.
Looking from a more micro perspective, we identified more than 5 major competitors in the market which are likely the counterparts of us. With the decided comparing metrics, we made market research for the evaluation of our Sugar Fox Company’s potential future competitiveness and the aspects that we will be investing more resources in for improvements.
Therefore, pulling out the metric of effectiveness and costliness, we can have the following visual measurement for our Sugar Fox company.
Figure 3. Competitive analysis map
In conclusion, with the metrics and comparisons in hand, we become clear about the possible future strategy, with the press on acquiring a green channel for the clinic trials from the Chinese government, accumulating clinic successful trails in order to enter the national medical insurance list, and promoting the brand awareness among the targeted customers to catch up with our predecessor competitors.
In order to make it more clear about our future business development, please see the following milestones we prospect as a primary reference.
Figure 4. Timeline of our business development
1. Preclinical studies
The goal of the first phase of drug development is to complete the preclinical toxicology study, which requires the developer to deliver the first batch of API (Active Pharmaceutical Ingredient) as quickly as possible.
2. IND declaration (about 60 days)
IND is an Investigation of a New Drug. In short, a series of preclinical trials are required to be reported to the NMPA for clinical trials. NMPA is collectively called National Products Administration.
3. Clinical trials (3-7 years)
Clinical trials are conducted on people and are divided into three parts:
① Phase I clinical trial
The test subjects were ordinary people, and the samples were generally 20~100.
② Phase II clinical trial
The test subjects are patients with the target indication, and the sample is generally 60-300.
③ Phase III clinical trial
The test subjects were patients with target indications, and the sample was generally 300~2000 cases.
In addition, if a drug is imported or exported locally, it must be tested again. At a minimum, phase iii confirmatory clinical trials should be done to ensure no ethnic differences in use and dosage among populations.
4. New drug application
After an innovative drug completes a preclinical phase 3 study, the researchers analyze all the information and data, and the safety and efficacy of the drug are demonstrated, the company can submit a new Drug application to the Drug Regulatory Agency (C) FDA.
1. The NDA or BLA
After the clinical trial is completed, an NDA or BLA is submitted to the FDA for marketing approval.
2. Phase IV clinical trial
Phase iv clinical trial is to strengthen monitoring in the practical application process of new drugs after marketing and to continue investigating the efficacy and adverse reactions in broader and longer practical Applications.
3. Determine the unit price of the drug
Since the drug is not an anesthetic, the unit price does not need to be determined by the government but can be set by the enterprise. We plan to use the most classic pricing technique, cost plus, where we can first determine profit, then forecast sales volume, and then assess unit price
1. Get good feedback
2. Drugs are profitable
1. Step into foreign markets
2. Sign the contract according to the quality requirements of the foreign consignee
1. Approval after listing (4-10 years after listing)
The goal is to review the effectiveness and safety of an NDA, or BLA, because there are still risks, such as Avandia, GlaxoSmithKline's blockbuster diabetes drug, which had to be pulled from the market after a spike in heart attacks and sudden death. So it needs to be approved again after it's on the market.
1. China's largest drug company which has the largest market capitalization
2. Peak sales (period: 2030-2035 6 years)
In discussing the application concerns and challenges, we divided three phases for specialized consideration. Below is the overview map for the reference.
1. Technical Obstacles
The high professional skills and controlled biomedical targeting resolution and the requirement for reducing the side effect of inhibiting all FoxO1genes in the body.
2. Finance Funding
The investors are likely to be discouraged by the idea of entirely inventing a new innovative drug out of little combination with the old drugs.
3. Limitation
Our drug is not a solution to an extremely high sugar intake lifestyle.If the patient eats sugar indiscriminately, blood sugar may remain at abnormal levels which should then turn to traditional insulin intake method.
1. Ethical Practice
The trial stage of the drug might involve animal experiments and in the clinical trial stage, it will require human volunteers. All these might cause ethical concerns.
2. Sustaining Team Morale
There will be challenges even failure during the clinical trial, and we might get rejected in any stage. We have to maintain the courage to restart anytime.
1. Mass Production
(1) Total quality control
(2) Sustainable Production Management
355 couldn’t prompt beta cell secrete insulin directly. If the genes of resistance are activated, the prompter of G6Pase, PEPKC and PC could be activated. The key protein of AKT pathway, NF-kapaB couldn’t make sense in experiment. This was the reason that influenced the value of IC50 decreased.
1. Observation and Research Network. (2022, June 17).
2. International Diabetes Federation. (2021, September). Diabetes facts & figures.
