Team:SZU-China/Entrepreneurship
Entrepreneurship
In order to promote and apply our products in the market better, we designed a supporting health management application platform for IBD patients and even all patients with gastroenteropathy, so as to systematically connect patients' health education and management with adjuvant treatment of drugs and other links together.
This health management platform will realize patients' own health management through personalized diet customization, communication community and other plates.
Here, we present our considerations for bringing the Gutail Floractory to market with the health management platform.
This project is an IBD adjuvant and application platform based on genetic engineering and big data, which systematically integrates IBD patients' health education management and drug adjuvant therapy. Our drug development is based on synthetic biology techniques, using "plasmids" to arm lactic acid probiotics and E. coli to become engineered bacteria capable of continuously expressing therapeutic proteins at disease sites. In addition, through metagenomic analysis of patients' feces, we also use bioinformatics analysis and big data to customize drugs, so as to provide targeted treatment for patients. At the same time, we have built a health management platform to realize patients' health management with personalized diet customization, communication community and other functions.
This project is an IBD adjuvant and application platform based on genetic engineering and big data, which systematically integrates IBD patients' health education management and drug adjuvant therapy. Our drug development is based on synthetic biology techniques, using "plasmids" to arm lactic acid probiotics and E. coli to become engineered bacteria capable of continuously expressing therapeutic proteins at disease sites. In addition, through metagenomic analysis of patients' feces, we also use bioinformatics analysis and big data to customize drugs, so as to provide targeted treatment for patients. At the same time, we have built a health management platform to realize patients' health management with personalized diet customization, communication community and other functions.
IBD patient community function : Provide a platform for patient communication. Find comfort from the experience of others or in helping each other. To help IBD patients better adapt to the society, relieve the mental pressure brought by the disease.
The function of food diary : Provide standardized e-form,to enable patients to better record diet Functions: (1) Help patients find a personalized diet that works for them; ② As feedback for drug customization
Drug customization process :
① After the patient purchases the service, we will mail the stool sampling kit to him.
② Patients collect their own stool and send it back.
③ We perform metagenomic sequencing on stool samples to understand the proportion of intestinal flora in patients. So that we can determine the usage and proportion of different engineering bacteria to accurately， so as to effectively regulate the proportion of patient's intestinal flora and promote intestinal recovery. And Screening effective therapeutic targets for different patients to accurately treat IBD.
④ According to the above analysis results, personalized customized drugs can be produced.
⑤ The patients have been treated with drugs and dietary management, and stool sequencing was performed again after one cycle of treatment. Observe the therapeutic effect and adjust the drug ratio again.
Fig.1 Product introduction.
Table 1 PEST Analysis.
1.Macro-Environmental Analysis
The separation of medicine and drug is one of the core contents of the medical and health system reform (new medical reform) in China mainland, which is an important measure to change the current situation of supporting medicine with drugs. "Medical separation" aims to establish the competition mechanism of drug circulation and cut off the economic interest relationship between hospitals, medical staff, and drug marketers. Under the background of this policy, it is more likely for patients to independently choose treatment plans, providing new opportunities for our products to enter the market.
China continues to provide policy support for pharmaceutical innovation and development, further guiding pharmaceutical enterprises to increase R&D investment and supporting innovation in the pharmaceutical industry. This will help more skill new drugs enter the market, facilitate and support our products in the process of review, approval, production and circulation.
Domestic health demand is strong, and health consumption exceeds supply. In 2019, the per capita consumption expenditure on healthcare exceeded 1,900 yuan, with an overall compound growth rate of over 10% during the 13th Five-Year Plan period.
At present, the market scale of Internet medical content mainly comes from B-end business income (professional customized medical content, digital marketing of pharmaceutical enterprises). Revenue such as C-end knowledge payment is in the growth stage of business realization, accounting for less than 1%. With the increasing maturity of image recognition technology and AI diagnosis, tool-based medical content will become a carrier form of stickier and higher barriers, and the overall Internet medical vertical content market will achieve explosive growth. Iresearch is expected to reach 6.9 billion yuan in 2023. Among them, the revenue proportion of C-end business is expected to exceed that of B-end business in 2022 and exceed 60% in 2023, entering the mature stage of commercial liquidation.
Internet medical content is mainly aimed at the mass consumer end, with little patient education-related content. Moreover, the energy of clinical medical staff is limited, the implementation of health education and follow-up work is not optimistic, and there is a lack of patient-oriented medical vertical content. Health education, health management, psychological counseling and other functions in our products are in urgent need, which is of great significance.
Among the eight popular science topics, health and medical care ranked first with 63.16%, and 39% of users would search online first if they were ill. As more and more users take the initiative to learn medical and health knowledge, the "Internet + Medical" industry has a vast space for development.
The traditional marketing model of pharmaceutical enterprises with pharmaceutical representatives as the core has been affected by the policy of medical separation and the epidemic, and will gradually change to the digital marketing model. Among them, the medical vertical content platform will carry the marketing needs of the doctor and become a key link in the digital marketing of pharmaceutical enterprises, which will be further combined. Our product sales approach based on the app platform is in line with the transformation trend of digital marketing development, which will reach users more accurately, simplify drug access channels and reduce drug costs for patients.
In recent years, the incidence of chronic diseases in China has risen, and the number of patients with chronic diseases has reached 370 million. The disease burden caused by chronic diseases accounts for nearly 70% of the total disease burden. Among the top 10 best-selling drugs in the world in 2017, biological macromolecular drugs occupy 6 seats. The rapid development of life science and biotechnology has promoted the development of biological medicines. Our drug research and development is based on the cutting-edge research achievements of synthetic biology, molecular biology, genomics and other disciplines, with substantial technological advantages.
In January this year, the AGA (American Gastroenterological Association) published clinical Practice Guidelines for the Management of Moderate to Severe Ulcerative Colitis, which recommended the early use of biological agents in patients with moderate to severe UC rather than gradually ascending the treatment ladder. This means that moderate and severe IBD treatment is accelerating into the era of biologics as the core.
Fig.2 Engineering bacterial drugs are widely used in major diseases
Currently, the use of synthetic biology genetic modification of probiotics, namely the research and development of engineered bacteria drugs is in full swing, which has been widely used in the treatment of metabolic diseases, inflammation, cancer and other diseases, and the technology is relatively mature. Our IBD adjuvant drug leverages synthetic biology genetic modification of probiotics to treat IBD, capturing the trend of technological development in the industry.
2.Industry Market Analysis
Fig.3 IBD pharmaceutical treatment industry market size and forecast from 2015 to 2022.
The number of IBD patients in China is on the rise, which stimulates the increasing demand for IBD drug therapy market. In the past five years, the market size of IBD drug therapy in China increased from 6.27 billion yuan in 2014 to 8.09 billion yuan in 2019, with a five-year compound growth rate of 6.6%. It is expected that in the next five years, the IBD drug therapy market size in China will maintain a continuous growth trend, and is expected to exceed 10 billion yuan by 2024, with a compound annual growth rate of 5.5%.
At present, the uncertainty of the pathogenesis of IBD and the universality of pathogenic factors significantly improve the difficulty of IBD targeted drug therapy. It is challenging to develop a unified treatment plan for different patients in clinical practice, and personalized treatment is gradually adopted in the industry because of its necessity.
3.Market Demand Analysis
There is currently a significant unmet clinical need for safety and compliance in the IBD drug market, despite the presence of multiple biologics on the market.
IFX remains the first-line treatment of choice among many marketed biologics. At the same time, Vedolizumab and other anti-TNFα, as well as Ustekinumab and JAK inhibitors, can also occupy a portion of the patient population due to their different M0A, superior route of administration or cost-benefit ratio. However, the existing clinical data shows that the proportion of complete clinical remission of moderate and severe IBD is about 50%. Moreover, patients who achieve clinical remission still face a certain proportion of relapse and drug resistance, and their safety and compliance are still not satisfied in the large unmet clinical needs.
Inflammatory bowel disease (IBD) is an idiopathic inflammatory bowel disease that affects the ileum, rectum and colon. Including ulcerative colitis (UC) and Crohn's disease (CD) two subtypes. In recent years, the incidence of IBD has increased significantly in China. According to the survey data in 2016, the total incidence of IBD was about 3.14/100,000. It is expected that the number of cases will reach 1.5 million in 2025, and the age of onset is mainly concentrated in 25-40 years old. Based on the above user portraits, we can find that IBD patients have demands that current market products cannot directly meet in the aspects of diet guidance, diet management, health knowledge and psychological counseling. Therefore, we designed functions on the APP according to the characteristics of IBD patients, and opened up a new digital marketing mode by opening up the sales link of drugs.
Although our health education management platform is open to all patients with gastroenteropathy, its primary revenue comes from VIP customers in these groups, as well as supplemental treatment income from moderately well-off IBD patients and above groups. These people are more willing to spend on their own diet health and supplemental treatment.
Our target customers first focus on the economically developed coastal areas in China, who can pay more for treatment and are more willing to accept other auxiliary treatments in addition to hospital treatment.
The product belongs to the type of product specialization. We constantly optimize the functional design of the platform according to the needs of IBD patients, which helps us establish a good image in related fields and reflect the high quality of the competition among different people. Lay a good foundation for the subsequent development and deployment of the platform from IBD to total digestive system diseases.
Our program is dedicated to the systematic integration of IBD patients' health education management and adjuvant medication. In the process of drug research and development, we introduce fecal analysis technology to achieve the purpose of "diagnosis -- stool sampling -- bioinformatic analysis -- personalized drug administration assisted treatment -- daily education and health management -- follow-up visit -- adjusting drug formulation ratio", which is different from other drugs with its accuracy, adjustability and personalized characteristics. Regarding health management platform construction, we focus on IBD disease and form differentiated competitive advantages with other food recording platforms. At the same time, the IBD communication community and patient story-sharing area were constructed to reflect the spirit of caring for patients.
Fig.4 Analysis of Competitive Products for IBD Therapeutics.
Table 2 Product comparison.
Some other genetically engineered bacteria drugs used to treat IBD are shown in the following figure:
Fig.5 Main genetically engineered bacteria drugs for the treatment of IBD
In summary, the existing competing engineering bacteria drugs have the problems of low treatment efficiency, inability in customization and treatment of the corresponding target. Our drug products uses cocktail therapy, refer to the results of fecal analysis, it can obtain the specific intestinal flora and metabolites missing in IBD patients, and supply them quantitatively and efficiently, so as to achieve long-term relief of IBD.
Analysis of Competing Products on the Diet Record Platform
Table 3 Analysis for food record platform competitive products.
4.Technological Advantages
Effectively Reduce Side Effects
Safety is always an important goal of chronic medicine. In this regard, our team made efforts in the following two aspects:
Considering the safety of human intestinal drugs, our team selected lactococcus lactis and E.coli Nissle 1917, both of which have been proved to be safe, as our engineering bacterial chassis. In the selection of plasmid, we also take full consideration to avoid the risk of gene transfer.
We used acid sensitivity promoters as switches (kill switches) to ensure that engineered bacteria could start or stop treatment under tightly restricted conditions and would not be leaked into the environment or human blood.
Effectively Prevent IBD Recurrence
Compliance is also an important factor in preventing recurrence for IBD. The engineered bacteria of our project will colonize the intestine for several weeks to several months, and continuously release therapeutic active substances, so as to reduce The Times of medication, achieve long-term inflammation relief, maintain the balance of intestinal flora and intestinal health of patients, and prevent the recurrence of IBD and other related diseases.
Advantages Over Natural Bacteria
Compared to natural bacteria only in terms of percentage of the impact on the number of intestinal flora, our genetic engineering bacteria targeted starting from the treatment factors of IBD, heterologous expression from polymorphic bacteroidetes thioester enzymes to produce butyric acid, to promote the repair of intestinal epithelial cells, consolidate the intestinal mucosal barrier, inhibit the inflammatory pathway, the purpose of slow release inflammatory response; Human antibacterial peptide LL37 was expressed to reduce the harm of endotoxin to human body; Heterologous expression of superoxide dismutase to clear excess reactive oxygen metabolites in the affected area, reduce the peroxidation reaction in the inflamed colon, and slow down intestinal injury; The allogenic expression of biliary salinolytic enzyme reverses the impaired bile acid metabolism caused by the insufficient activity of microbial biliary salinolytic enzyme in the intestinal tract of patients, releasing inflammation slowly, and realizing the accurate treatment of multi-angle and multi-factor.
for Targeted Treatment of Patients
We rely on the "Xstrain technology" of The Company, the integrated public data set of the company and the massive microflora data of healthy individuals and patients with various indications before and after treatment, focus on the intestinal microflora differences of IBD patients, and customize the exclusive treatment plan and dietary guidance.
Medication Compliance of Patients
Relying on the freeze-drying research and development platform built by Xbiome, our team produced new intestinal flora preparations. It is more stable in the process of transportation and storage, while isolating the damage of oxygen and air humidity to intestinal bacteria, effectively masking the unpleasant smell of intestinal bacteria, easy to swallow and can be dispersed in a variety of solvents, and can effectively protect intestinal bacteria through the digestive tract and targeted release in the process of delivery.In its final form, microcapsules may also be stored in a medium such as yogurt or jelly to improve patient compliance.
1.Market Insight and Target Market
According to the preliminary market research, our target group is positioned as the IBD patient group with moderate prosperity and above. These groups often face demands for dietary guidance, dietary management, health knowledge and psychological counseling. At the same time, this group of people can afford more than the cost of treatment, and they are willing to receive other complementary treatment outside hospital.
2.Core Strategy
We mainly adopt a differentiation strategy committed to systematically integrating IBD patients' health education management and drug adjuvant therapy.
In the process of drug research and development, we introduce fecal analysis technology to achieve the purpose of "diagnosis -- stool sampling -- bioinformatic analysis -- personalized drug administration and assisted treatment -- daily education and health management -- follow-up visit -- adjusting drug formulation ratio", which is different from other drugs with its accuracy, adjustability and personalized characteristics.
In terms of the health management platform, we focus on IBD disease and form differentiated competitive advantages with other food recording platforms. At the same time, the IBD patient community and patient story-sharing area were constructed to reflect the spirit of caring for patients fully.
3.Marketing Strategy
Fig.6 Marketing strategy.
1.Start-Up Stage
Start-up stage target: Based on the market in South China, build a brand recognition.
Strategic planning: Initially establish cooperative relations with public hospitals and specialized clinics in South China. Meanwhile, use We-Media channel matrix and official publicity channels for market promotion. In addition, we will build an initial adjuvant development and application platform as soon as possible, and invite some psychological experts and doctors to register for certification and enter the platform.
After acquiring the first batch of seed users of the platform, we will guide and encourage users to use the functions of the platform, including IBD forum, colonization drugs, diet record and other functions,to enhance user viscosity, improve user activity, and actively expand the scope of business to office workers and middle-aged and elderly by promotion.
2.Growth Stage
Growth-Stage target: to develop the domestic market and serve patients all over the country.
Strategic planning: Cooperate with well-known hospitals nationwide; Combined with the local situation, carry on the marketing model copy; Further strengthen brand recognition; Improve the upstream and downstream supply chain.
Facilitating user fission; Increase the number of platform users, make caring for intestinal health a daily routine, Further active users to communicate, share and interact with each other on the platform, carry out some lectures on intestinal health and diet adjustment for the public, and go into the community to carry out point-to-point health propaganda, so as to gain greater popularity. Increase the volume of platform users and make caring for intestinal health a daily routine. Further encourage users to exchange and share, interactive posting and using other functions within the platform. At the same time, some lectures on intestinal health and dietary conditioning will be held for the public, and peer-to-peer health promotion was carried out in the community to gain greater popularity.
3.Mature Stage
Mature-stage target: To give consideration to economic and social benefits and provide ideas for prevention and treatment of gastroenteropathy.
Strategic planning: Improve the ecological closed-loop of adjuvant research and development. Starting from the steps of customized medicine, fecal analysis, drug delivery, health management, reexamination and screening, it effectively provides help for the disease control and treatment of patients with gastroenteropathy.
Attract more users to try to pay. At the same time, carry out "intestinal health public welfare action" and other activities. Go down to the village, carry out intestinal health propaganda, and provide free stool analysis experience services. In addition, we can collect intestinal flora samples from different regions, develop targeted new drugs, and reach cooperation agreements with the Health Commission and other government agencies to undertake part of the work, contributing to the development of intestinal health work in China.
Product Strategy
Common services include diet records, feedback on results, and recipe customization. We will provide users with personalized recipes after a one-week recording cycle according to the user's recording results, combined with the user's relevant health data (height, weight, body fat rate, etc.) and big data in the backstage. And after the daily diet record is completed, feedback diet adjustment suggestions in time. At the same time, the standardized recipe output function is provided to facilitate users to consult and communicate with clinicians about their recipe output.
①Detailed meal planning service: Unlike other meal plan services, users are required to take a stool detection beforehand. The test result is later uploaded to our database as a part of the baseline information and our users will be able to see the test result synchronously. Gut microbiota information along with medical history and other data previously stored are then collected, aiding the algorithm to form a full and detailed meal plan to our users. The feces test results is updated on a one-month basis.
②Personalized cocktail therapy service: The service includes detailed meal planning service. Which drug to use and how much our users receive are intelligently customized according to their intestinal microbiota and physical conditions. After the therapy begins, the system will update relevant information on a one-month basis, keeping drug proportion up to date so that duration of response requirements are met and therapeutic effect is maximized.
1.Market Introduction Stage
At the initial stage of entering the market, we will actively look for "Business" customers, such as medical institutions and gastroenterology departments of hospitals, by offering "Business" customers a discount of about 30% and providing all-round after-sales services. It is beneficial for our products to form word of mouth among consumers in the way of authoritative recommendation.
2.Expansion Period
During this period, we will stabilize the pricing for "Business" customers and gradually reduce the discounts. At the same time, it will shift its focus to "Consumer" customer fission, give "Consumer" customers preferential individual orders, and conduct customer fission through group purchase and other modes.
3.Mature Period
Our main strategy is to stabilize the pricing system, find the equilibrium between market demand and profit, and optimize the pricing system through the feedback from the "Business" and "Consumer" customer.
1.Backward integration
We will set up R&D headquarters and testing center in Shenzhen, and one to three testing branches in each province.
At the initial stage of the project entering the market, we will cooperate with local testing centers to reduce the cost of expansion. In the later stage of development, it will gradually establish its own regional testing divisions to improve management efficiency.
At the same time, due to the relatively developed economy in coastal areas and the concentration of target customer groups, we plan to set up some testing branches around the first and second-tier coastal cities such as Shanghai and Shenzhen to improve efficiency.
2.Forward integration
We use the Internet and direct sales team to promote and sell products directly, so as to reduce distribution costs. While making more competitive prices for products, we can also better predict product demand.
Gutail Floractory is a program providing health care mainly for IBD patients. Our service includes an online platform for health information and medicines as ancillary therapies. The program is based on close cooperation with Shenzhen University, Xbiome Co. Ltd., the 2nd People’s Hospital of Shenzhen as well as Southern University of Science and Technology. With a focus of IBD, the program provides with more specialized contents compared with other diet management platforms. “Love and warmth” is always our promise for patients.
The targeted clients of Gutail Floractory program include medical institutions, community health care subsidized by governments and individual patients of gastrointesinal diseases (especially IBD patients). Specialized customer support is provided for better experience: a personal health consultant is in service, combined with AI customer support. The program relies on contact with pharmaceutical sales representatives to increase our customer base.
The main project costs include raw materials, research and development fees, publicity costs, labor costs, operating costs, and other financial costs. Profits will be gained through IBD drug charges and stool test package charges, and we will make an overall strategic plan for the initial stage, growth stage and maturity stage.
1.Product Model
Macroeconomic, industry market, and market demand analysis all indicate a significant unmet clinical need in the field of IBD treatment.
The engineered bacteria in our project take into account both safety and compliance requirements. Firstly, the safe natural bacteria was selected as the engineering bacteria chassis, and the suicide switch was also set to prevent its leakage. Second, our engineered bacteria will colonize the gut for weeks to months. It can continuously release therapeutic active substances. Patients can effectively prevent recurrence of IBD and other related diseases without repeated use of drugs.
Our product positioning is: help IBD patients to carry out health education and health management; Adjunctive therapy with medication.
In the process of drug research and development, we introduce fecal analysis technology, and through the process of "diagnosis -- fecal sampling -- biogenic analysis -- personalized drug administration assisted treatment -- daily education and health management -- follow-up visit -- adjusting drug formulation ratio", we distinguish ourselves from other drugs with characteristics of accuracy, adjustability and individuation.
In terms of health management platform construction, we focus on IBD disease and form differentiated competitive advantages with other food recording platforms. At the same time, the IBD communication community and patient story-sharing area were constructed to reflect the spirit of caring for patients fully.
Our value proposition is comprehensive care for customers, to provide warm service for patients. Patients suffering from various kinds of gastroenteritis often have some psychological issues or psychological pressure. We hope that through the meticulous reflection of care, we let patients feel warm and let customers trust us.
2.Customer Model
To Business Customer: Hospitals, Medical institutions, Grassroots governments providing health services, etc.
To Consumer Customer: Patients with IBD and other gastroenteric diseases.
Good customer relations require courtesy, professionalism and effective response. Therefore, in terms of maintaining customer relations, we will set up a system of personal health butler + machine customer service.
Exclusive customer service will solve customer personalized problems to meet the unique needs of different customers;
Machine customer service to collect basic information, complete simple communication with customers and other programmed tasks;
We will also take the initiative to regularly visit customers and other activities to create a caring corporate image. All aspects, multi-level care for users, so that users can experience the general warmth like family care.
Fig.7 Profit model.
3.Cost Intensive
The cost structure of this project mainly includes raw materials, research and development costs, publicity activity costs, human resources costs, operating costs, and other financial expenses.
4.Partnership
The main partners of the project are as follows:
① Raw material supplier: Provide us with various raw materials needed for drug research and development;
② Shenzhen Xbiome Co., Ltd.: Carry out in-depth cooperation and exchanges with our project in experimental promotion, bio-information platform construction, data sharing, drug development and approval procedures.
③ Express and other similar service providers: Responsible for fecal testing logistics.
④ Cooperative hospitals such as Shenzhen Second People's Hospital: Provide clinical data to help us improve and upgrade our products.
⑤ School exchanges: We cooperated with the 2021 iGEM competition team of the Southern University of Science and Technology and reached a long-term, in-depth cooperation relationship to exchange experience and data with each other in experiments and modeling.
⑥ Community cooperation: To better promote our products, we will cooperate with significant communities in Shenzhen to better popularize intestinal health knowledge for the public.
Fig.8 Expected revenue after formal operation of the project. (Unit: Ten million RMB)
The project income is mainly based on the sales of IBD treatment drugs and the cost of stool testing.
The school will provide certain experimental research and development, funding and other support for this project. At the same time, Shenzhen Weijun Biotechnology Co., Ltd. will also provide raw materials and technical support. The team will continue to improve the pre-clinical research of the project, and then submit an IND application and NDA application. After passing the FDA certification, the production scale of the product will be gradually expanded to achieve mass production.
The "intestinal" Jijiu'an project is expected to turn into a profit after entering the market for the third year and realize positive income; it is expected that the equity will return to the initial value in the fifth year and shareholders will realize profits.
Fig.9 Future development strategy.
With the continuous collection of sample data, the maturity of the bioinformatics database system is also constantly improving. While carrying out targeted drug therapy to different patients, their general pathological signs of intestinal diseases are also constantly memorizing, learning, improving and optimizing in the collection and integration, laying a solid foundation for the expansion of subsequent treatment.
Meanwhile, we have also expanded our business scope to more intestinal diseases, thereby expanding the scope of the project audience and realizing profitability. In the targeted therapy of IBD, we will continue to add and improve the concept of "cocktail therapy" in addition to the four targets based on the existing technology, increase scientific research investment, expand current targets, and complete product close loop. We hope to increase the diversity of formula engineering bacteria, and strive to achieve diversified and refined treatment purposes, so as to improve the quality of life of patients and realize the vision of "intestinal" long-term security.
