Over the past six months, our team has made significant efforts in business transformation and has achieved remarkable progress.

Here are the key steps and outcomes we have taken:

• Stakeholder Analysis: We first conducted a comprehensive analysis of potential stakeholders, identifying their needs, expectations, and influence, and assessing their level of support for our business plan.
• Establishing Contacts: Based on the analysis results, we developed a detailed communication and engagement plan. We established connections with stakeholders through various channels, including face-to-face meetings, phone calls, emails, etc.
• Deepening Relationships: We not only established connections with stakeholders but also worked hard to deepen these relationships. We maintained and strengthened these relationships by regularly updating project progress.
• Investor Relations: We placed special emphasis on relationships with potential investors. We prepared a business plan to showcase our business model and growth potential. In addition, we organized 6 roadshows and participated in 3 startup competitions to showcase our project through various opportunities, and have already achieved some results.
• Customer Feedback: We actively collect and analyze feedback from potential customers to understand their views on our products or services. This feedback helps us improve our products and better meet market demands.
• Regulatory Compliance: We ensure that our business plan and operations comply with all relevant laws and regulatory requirements. We maintain open communication with regulatory authorities to ensure our compliance and stay informed about any regulatory changes that may affect our business. At the same time, we have made full preparations for patent applications.
• Team Building: We have strengthened internal team building, ensuring that each member understands their role and responsibilities and can communicate effectively with stakeholders.
• Risk Management: We identified risks that may affect our business transformation process, conducted a SWOT analysis of our products, and developed corresponding risk management plans. This includes market risks, financial risks, and operational risks.
• Continuous Improvement: We continuously evaluate our business transformation strategy and adjust it according to market feedback and business development. Our goal is to continuously improve our products and services to meet the changing market demands.

Business Plan - "Never Fight an Unprepared War"

Product Positioning

• Target Market: Patients with colorectal cancer, particularly those who have not responded well to traditional chemotherapy drugs.
• Competitive Advantage: High efficiency, safety, and cost-effectiveness.

Research and Development Plan

• Preclinical Research: Continue with in vitro and in vivo experiments to verify the safety and efficacy of Curmino.
• Clinical Trials: Apply for clinical trial permissions for Curmino and conduct Phase I, II, and III clinical trials to assess its safety, dose-response, efficacy, and side effects.
• Product Optimization: Iterate Curmino based on clinical trial feedback to improve efficacy and patient compliance.

Market Analysis

• Market Demand: Analyze the current status and future trends of the colorectal cancer treatment market, including market size, growth rate, and market demand drivers.
• Competitive Analysis: In-depth study of the product lines, market share, market strategies, strengths, and weaknesses of EcN applications and cancer treatments.
• Customer Profiling: Identify target customer groups, including public hospitals, insurance companies, and colorectal cancer patients, and understand their needs and preferences.

Marketing Strategy

• Brand Building: Establish the brand image of Curmino, emphasizing its innovation and therapeutic effects, and enhance brand visibility through scientific publications, patent applications, public relations activities, and industry awards.
• Educational Promotion: Participate in academic conferences and online medical course platforms on probiotics applications and new cancer therapies to educate healthcare professionals and patients, raising awareness of Curmino's therapeutic potential.
• Co-marketing: Establish cooperative relationships with medical institutions, pharmaceutical companies, and insurance companies to jointly promote Curmino and expand market coverage.

Sales Strategy

• Direct Sales: Build a professional direct sales team to sell Curmino products directly to public hospitals specializing in cancer treatment.
• Distribution Channels: Collaborate with pharmaceutical representatives, pharmaceutical companies, and other distributors to establish an extensive sales network, ensuring product accessibility in various regions.
• Pricing Strategy: Develop a reasonable pricing strategy based on market research and cost analysis of colorectal cancer treatment drugs to attract colorectal cancer patients while ensuring a good profit margin.

Production Plan

• Production Facilities: Establish GMP-standard production facilities to ensure product quality and production efficiency.
• Supply Chain Management: Implement strict supply chain management to ensure the quality and stable supply of raw materials EcN.
• Quality Control: Establish a strict quality control system to ensure that every step of the product, from production to sales, meets the standards of probiotics application drugs.

Financial Planning

• Cost Budgeting: Detailed calculation of the costs associated with Curmino R&D, production, marketing, and operations, including direct and indirect costs.
• Revenue Forecast: Forecast sales and profits after the Curmino product launches based on market analysis and sales strategy.
• Risk Assessment: Assess market risks, technical risks, team risks, intellectual property risks, etc., and develop corresponding risk management and mitigation strategies.

Legal and Regulatory

• Patent Applications: Protect the intellectual property of Curmino by applying for relevant patents to ensure market exclusivity.
• Regulatory Compliance: Ensure that product development and promotional activities comply with all relevant medical regulations and standards.

Team Building

• Core Team: Form a team composed of interdisciplinary experts, including PIs in bacterial therapy development, marketing personnel, and management personnel, to jointly promote the renewal and commercialization of Curmino products.
• Advisory Team: Hire legal and investment advisors deeply involved in the biopharmaceutical industry to provide guidance and advice on the development and market strategy of Curmino.

Timeline

• Short-term Goals (1-2 years): Complete preclinical research, apply for and obtain clinical trial permissions, and begin Phase I clinical trials.
• Medium-term Goals (3-5 years): Complete Phase II and III clinical trials, submit new drug applications, and obtain market entry permissions.
• Long-term Goals (5-10 years): Expand market share globally, continue to iterate Curmino products, attempt to develop bacterial therapies for other types of cancer, and become a leading brand in the field of colorectal cancer treatment and the broader cancer treatment field.

Milestones

• Completion of Preclinical Research: 2025
• Completion of Phase I Clinical Trial: 2026
• Product Launch: 2028
• Market Share Target: 2030, become a major player in the field of colorectal cancer treatment.

Business Model Canvas

Currently, the number of newly diagnosed cancer cases worldwide is reaching record highs, with colorectal cancer accounting for 9.7% of all malignant tumor incidences, ranking third globally. Within this, the incidence rates of colon and rectal cancer are almost equal, with a high proportion of low rectal cancer, constituting 60% to 75% of the total incidence of rectal cancer. However, current treatment methods for mid and low rectal cancer are quite limited, making it difficult to achieve safe and effective treatment, with a persistently high mortality rate; surgical methods also struggle to avoid the removal of the anus, which significantly reduces the quality of life for patients. These issues have spurred a strong demand for new treatment methods for mid and low rectal cancer. At the same time, patient expectations are continuously evolving, with an increasing number of patients seeking new treatment methods that can ensure both safe and effective therapeutic outcomes and their quality of life. Currently, when considering treatment, patients primarily focus on the effectiveness, safety, and post-treatment quality of life.

Our Curmino was created to address these needs. It combines bacterial therapy with bioorthogonal chemical reactions and utilizes synthetic biology methods to introduce a suicide gene, bringing new hope for the treatment of mid and low rectal cancer. Through the bacteria's colonization effect on cancer, it can be precisely delivered into cancer cells. Combined with bioorthogonal chemical reactions, drugs can be efficiently delivered to the hypoxic and necrotic areas of mid and low rectal cancer. This new method greatly overcomes the issues of drug leakage and severe toxicity by enhancing the target specificity and therapeutic index of cancer treatment drugs. Furthermore, the introduction of the suicide gene not only deactivates the bacteria when they are out of the body, making it environmentally friendly, but also allows for the bacterial treatment to be stopped at any time, ensuring true safety.

Group Background Survey

Middle and low rectal cancer is a type of colorectal cancer. According to global statistical data, there were approximately 1.926 million new cases of colorectal cancer worldwide in 2022, ranking it the third most common malignant tumor globally. In China, the incidence and mortality rates of colorectal cancer are on the rise, with about 517,100 new cases of colorectal cancer in 2022, accounting for 10.7% of all new cancer cases.

Group Reality Survey

The incidence of middle and low rectal cancer is increasing, especially among the elderly population. Middle and low rectal cancer usually occurs in the middle and lower parts of the rectum, close to the anus, making surgery more difficult and the risk of lymph node metastasis higher. According to the Chinese tumor registration annual report, the incidence rate of colorectal cancer in males is higher than in females, and the urban area is higher than the rural area.

User Pain Point Analysis

Middle and low rectal cancer patients face the following main problems:

Treatment Options

Surgery is the main treatment method, but the surgery is complex and may require stoma creation, affecting the quality of life. The radical surgery recommends total mesorectal excision (TME).

For patients with middle and high rectal cancer, a far resection margin of 5 cm is sufficient, while for patients with low rectal cancer, a near resection margin of 1-2 cm is acceptable, and intraoperative frozen pathology should be used to confirm the negative resection margin.

Recurrence Risk

Even after treatment, there is a risk of recurrence, and regular monitoring is needed. The recommended follow-up frequency for stages Ⅰ to Ⅲ CRC after surgery:

• Stage Ⅰ, once every 6 months for 5 years;
• Stages Ⅱ to Ⅲ, once every 3 months for 3 years, then once every 6 months until 5 years after surgery; once a year after 5 years.

Psychological Burden

The psychological pressure brought by cancer diagnosis and treatment, especially for patients who need stoma creation.

Economic Burden

The cost of treatment is high, and the economic burden is heavy.

The treatment costs include surgery, chemotherapy, radiotherapy, imaging assessment, pathological assessment, and endoscopy, among other diagnostic and treatment methods. The multidisciplinary team (MDT) model can improve the level of colorectal cancer diagnosis and treatment.

Application scenarios

(1)For early-stage tumors, EcN is delivered orally in the form of enteric-coated capsules made from bacterial dry powder.

(2)For mid to late-stage tumors, it assists in the delivery of chemotherapeutic drugs.

(3)In the clinical setting prior to surgery, it can reduce tumor volume and assist in tumor excision.

Unique advantages

(1)EcN is a probiotic with a self-destruct system

— it has minimal side effects and does not remain in the body after discontinuation of use.

(2)Local administration provides a high concentration

— leading to good effects and a lower chance of recurrence.

(3)Sustainable delivery

— cost-effective.

(4)Oral delivery form

— reducing patient pain, protects mental health, and improves medication compliance.

Market size

Colorectal cancer is the third most common cancer globally and the second leading cause of cancer-related deaths. With the aging global population and the rise of unhealthy lifestyles, the incidence of colorectal cancer is on the rise. It is projected that by 2032, the global market for colorectal cancer therapeutics will reach approximately $10.3 billion, reflecting the urgent demand for effective treatment options.

The main drivers of market growth include an emphasis on early screening and diagnosis of colorectal cancer, as well as the continuous development of new therapies. For instance, immunotherapy has made significant advancements in the treatment of colorectal cancer, especially for patients with tumors that have high microsatellite instability (MSI-H) or deficient mismatch repair (dMMR). Moreover, the increased approval of biosimilars has led to a greater variety of treatment options, helping to reduce treatment costs and improve the accessibility of medications.

However, the colorectal cancer therapeutics market also faces challenges, including the high cost of treatment and side effects associated with therapies. Furthermore, despite improvements in screening and treatment methods, the mortality rate for colorectal cancer remains high in many regions, indicating the need for further efforts to enhance prevention, early diagnosis, and treatment efficiency.

Overall, with the emergence of new therapies and the improvement of existing ones, it is expected that the market for colorectal cancer therapeutics will continue to grow in the coming years.

Market pain point

Currently, the main treatment method for middle and low rectal cancer is surgical intervention, supplemented by adjuvant radiotherapy, adjuvant chemotherapy, and adjuvant immunotherapy. After communicating with doctors, we understand the existing problems in the treatment:

• Traditional surgical treatment may have a high recurrence rate.
• Adjuvant radiotherapy may increase the risk of anastomotic leakage after surgery.
• Adjuvant chemotherapy may cause significant side effects.
• Adjuvant immunotherapy is prone to cause related adverse reactions.

Name

Curmino: a prodrug releasing bacterial therapy for colorectal cancer treatment

Introduction

Curmino is a colorectal cancer treating bacterial therapy that is developed by team PekingHSC 2024. We used the technique of genetic code expansion and displayed a great amount of tetrazine on the surface of E. coli Nissel 1917 (EcN), thus realizing accurate release of prodrug TCO-Dox at tumor microenvironment (TME). In our design, we fully considered the problem of tetrazine display, effective prodrug selection, and safety, thus compared with other bacterial therapy, we have the advantage of efficiency and safety.

Design Introduction

1.Tetrazine display on bacterial surface

In our design related to the presentation of tetrazine, after considering various factors such as the generation of curled fibers, the quantity of presentation, and the degree of presentation, we have ultimately achieved a level where 1OD bacteria can present tetrazine at the micromolar level, with a rapid and efficient response within 10 minutes.

2.Safe and Effective Prodrug selection

Prodrugs can ensure the safety of drugs in circulation, and by appropriately increasing the dosage and achieving precise release, they can effectively kill tumors more efficiently.

In our design, we have chosen Dox, a commonly used chemotherapeutic drug for the treatment of colorectal cancer. By restricting its toxicity with TCO, its tolerability is increased by tenfold, and it can be released into Dox in areas rich in tetrazine, which is where our bacteria are enriched, achieving more effective killing. In vitro cell experiments have achieved a 90% reduction in tumor cells under the release of 6μM drugs.

3.Safety Design

We not only focus on prodrugs but also incorporate other safety-related designs. For example, the presentation of tetrazine depends on promoters and unnatural amino acids. Tet v2.0 naturally accumulates in the tumor microenvironment, and the hypoxia promoter ensures that the protein is only expressed within the TME. Furthermore, we have knocked out the ThyA gene to ensure that the bacteria do not function outside the tumor microenvironment and have introduced a suicide gene to ensure that the therapy can be actively terminated at any time.

Core competence

1.Safety

In terms of bacterial strain selection, we have chosen Escherichia coli Nissle 1917 (EcN). It naturally colonizes the gut without causing excessive stimulation to the body and can naturally aggregate and proliferate near tumors, ensuring both safety and efficacy. Regarding the use of EcN, we have authored and published a white paper on EcN, thoroughly demonstrating its safety. The paper discusses EcN's history, characteristics, applications in cancer and inflammatory bowel disease (IBD) treatments, genetic modifications for therapeutic uses, and its market and safety prospects.

Regarding prodrugs, they ensure that the drug does not cause excessive stimulation to the body and can be naturally and safely metabolized; the bacteria determine the release site of the prodrug; Tet v2.0 will also naturally accumulate near tumors, ensuring that the bacteria can express proteins in the correct location and guaranteeing the timing of prodrug release. With validation from wet lab in vitro experiments, there is a variable concentration range of 10 times the Dox dose, ensuring safety from the mode of action.

Overall, from the selection of bacterial strains to the control of various time points for prodrug release, we have considered all aspects to ensure the safety of our design.

2.Efficacy

In terms of efficacy, we have utilized the Click-to-release principle for the release of chemotherapeutic drugs. The effectiveness of chemotherapeutic drugs is undoubted; the main issues lie more in safety. Our prodrug strategy greatly alleviates these safety concerns. In fact, some professors have combined it with antibodies for the development of MMAE prodrugs, which have already entered clinical trials. Compared to them, we have more tetrazine presentation, more controllable dynamics, and stronger tumor non-specific targeting, among other advantages. We have a strong computational biology team that has conducted detailed simulations and arguments regarding drug reactions and release processes, and our wet lab team has also validated in vitro experiments that at a concentration of 6μM, which is far below the safe concentration of TCO-Dox, the prodrug release strategy can achieve up to a 90% tumor suppression rate. Overall, we have fully utilized and combined the strengths of bacterial therapy and chemotherapy, creating a powerful alliance to achieve efficient tumor killing.

3.Well acknowledged work

The PekingHSC team has engaged in extensive communication with experts from various fields. Professors from the fields of bacterial therapy, gene editing, and pharmaceuticals have given us great affirmation from a scientific standpoint. On the corporate side, we have exchanged ideas on technical design with companies ranging from protein drug firms to oncolytic virus companies. Additionally, we have communicated with frontline doctors at Beijing Cancer Hospital to fully understand the needs and perspectives of both patients and medical professionals.

We have also participated in six roadshows, presenting our project in detail to experts in the fields of scientific translation, industrial incubation, and investment. Our project stood out among as many as 42,100 projects and entered the final round of investment project selection within China.

In summary, through our interactions with experts, we have refined our design step by step from various perspectives. but have also received ample affirmation and support for our product. We have conducted numerous and extensive exchanges and have received a lot of affirmation, making it a project worthy of trust.

Competitor Analysis

Synlogic Therapeutics

Using ECN as a chassis to transform cancer treatment

Introduction: Founded in Boston, USA in 2013, it was listed on the Nasdaq through a reverse merger in 2017. It uses synthetic biology technology to transform microorganisms, and repairs metabolic disorders in patients by synthesizing microorganisms carrying special DNA chains (gene circuits), thereby achieving the effect of treating related diseases.

Synlogic Therapeutics product pipeline

Ardeypharm

Live bacteria tablets

Introduction: Arderpharm, located in Herdecke, Germany, is a leading pharmaceutical expert in the development and production of probiotic drugs. EcN live bacteria tablets (mutaflor) are sold directly with EcN as the main ingredient.

Secretion-related proteins after EcN modification

Angeluo (Shenzhen) Biotechnology Co., Ltd.

Medicinal protein

Introduction: Angeluo (Shenzhen) Biotechnology Co., Ltd. was established on April 10, 2023. In the field of SOD development and application, it is one of the few synthetic biology companies in the world that has molecular acquisition, collision and gene transcription technology, and has achieved mass production on a large-scale industrial scale. The company is devoted to multidisciplinary cross-disciplinary research in biology, chemistry, etc., and provides green biotechnology solutions for applications in medicine, agriculture, food and other fields, as well as the supply of key raw materials.

Angeluo product display

SWOT analysis

Core staff

The PekingHsc team is a vibrant and diverse collective of ambitious students, each contributing uniquely to the wet lab, dry lab, human practice, and art divisions. Their division of labor is clear, and they have layout in many aspects such as clinical investigation, basic research, marketing, and publicity design.Their combined dedication helped them overcome difficulties in product development and successfully transitioned the team's identity. Comprising skilled individuals who are passionate, active, and supportive, they meticulously plan and execute their project stages. Together, they tackle obstacles and bring their vision to fruition.

Academic resources, technical support

The PekingHSC team was strongly supported by Peking university School of Pharmaceutical Sciences and State Key Laboratory Of Natural And Biomimetic Drugs, under the mentorship of three professors. Mr. Tao Liu is the primary PI of the team. His research focuses on chemical modification of protein drugs, gene editing, and cell therapy, and he has developed innovative protein drugs containing artificial amino drugs, which have been applied in various fields such as oncology and cell therapy. Mr. Zhengwei Xie serves as team’s secondary PI for dry lab. His research area focuses on the application of cross-disciplinary tools, including artificial intelligence and computational biology approaches,for mechanistic studies of aging and metabolic diseases. Mr.Yong Wang serves as the secondary PI of the team, and his main research area is protein drug development and research. Strong support was received from Peking university Health Science Center.

Sources of Funding

Early stage

We will seek funding support through investor roadshows and startup competitions. This will help us:

• Obtaining Feedback: By participating in investor roadshows and startup competitions, we are able to directly receive valuable feedback from potential investors and industry experts. This feedback is crucial for us to improve our products, services, and business model.
• Building Networks: Through these activities, we have the opportunity to connect with investors, industry experts, and other entrepreneurs. These connections are vital for our future development, as they may become our partners or advisors.
• Attracting Talent: By showcasing the potential and vision of our company, we hope to attract excellent talent to join our team. A strong team is key to achieving our goals.
• Raising Capital: Our goal is to secure the necessary seed funding through these activities. These funds will be used for product development, market promotion, and daily operations to ensure our project proceeds smoothly.
• Risk Diversification: By attracting a diverse range of investors, we can diversify risks and reduce reliance on a single source of funding. This helps us to advance the project more robustly.

Late stage

We anticipate implementing the project using the VIC model.

Under the VIC model, we will initially secure the necessary financial support through venture capital to purchase or develop promising intellectual properties, including drug formulations and treatment methods. Subsequently, we will collaborate with CROs (Contract Research Organizations), leveraging their expertise and facilities to conduct drug development work, including clinical trials and data analysis.

When implementing the VIC model, several key points should be noted.

• We should select the appropriate CRO partners,as their professional capabilities and service quality directly impact the success or failure of the research and development.
• We need to ensure the protection of intellectual property to prevent technology leaks or infringement.
• We need to maintain good communication with investors to ensure they have a clear understanding of the project's progress and potential returns.

BP Optimization Process

Peking University Innovation and Entrepreneurship Competition of Wuhan Cup

To test our business plan, we decided to participate in the Wuhan Cup. However, we were not successful in passing the pre-selection round of the competition.

After this setback, we approached Mr. Ping Tang, the instructor of the Life Sciences Industry Association at Peking University, and presented our business plan to him. He pointed out that our plan lacked a clear logic. Firstly, we had failed to analyze the market and the pain points of stakeholders, which meant that the importance and significance of our project were not emphasized. Secondly, he noted that our description of future planning was unprofessional.

Following this discussion, we rewrote the logic of our business plan, paying more attention to analyzing industry pain points and detailing our business technology.

Early Project Commercial Roadshow of Peking University Innovation and Entrepreneurship Society (Medical and Health Special Show)

After the failure of the Wuhan Cup, we rewrote our business plan (BP) and decided to try again. The second opportunity we found was an Early Project Commercial Roadshow at Peking University, which was not just a competition but also a platform where we could receive investments. The investors were experts from various backgrounds including informal investors, doctors, and established medical enterprises.

After presenting our business plan, the investors expressed concerns. Although we had improved our focus on market analysis and industry pain points, they believed our project was too early for investment discussions;we were still in the research phase rather than the transformation phase. They felt we did not have a clear vision for our product.

Indeed, at that time, we were still in the early stages of developing our product, primarily conducting scientific research, and many aspects, including the delivery method for our drug, remained unclear. Therefore, after the roadshow, we first returned to the research phase to achieve results that could demonstrate our product's efficacy and safety. Secondly, we began to consider what we were currently lacking as a product.

The First Chinese International College Students Innovation and Entrepreneurship Competition

By June, it was time for the First Chinese International College Students Innovation and Entrepreneurship Competition, so we submitted our project in the Innovative Medical Sciences track.

We submitted our first round of the business plan for the school match of the competition before the roadshow. Although we received first prize, along with the feedback we got from the roadshow, suggestions from Mr. Ping Tang and Mr. Xiaoming Zhang helped us to evolve the next generation of our business plan. Firstly, we significantly improved the design of our project by adding new logos and designs to the PowerPoint presentation, making it more readable. Secondly, we began to present a product rather than just focusing on the science.

Since we won the first prize in the school match, we were invited to participate in the Beijing competition. With the substantial improvements to our business plan, we performed successfully. The judges asked more questions about the background and design rather than pointing out flaws in our business plan. However, we still realized that our project might be quite difficult to understand, which was consistent with our experience at the CCiC competition, so we decided to improve upon this aspect.

At the same time, we consulted with a researcher from a well-known public mutual fund and a well-known investor (names withheld according to their requirements). They suggested that we should expand the significance of our project beyond just therapeutics and science to other fields as well. We were quite surprised because this aligned with the idea of iGEM. They also pointed out that, although better than before, our team composition, financial situation, and business model canvas were still somewhat disorganized. Therefore, for the next generation of our business plan, we made improvements in the following areas:

• A clearer background explanation of our project and product.
• A section that not only covers business but also expands our significance in educational fields.
• An improved team composition and financial situation.
• A new business model canvas.

Future competition: National competition of The First Chinese International College Students Innovation and Entrepreneurship Competition and Peking University 1898 Innovation and Entrepreneurship Competition

After the modifications, we submitted our business plan to more competitions, including the national round of the First Chinese International College Students Innovation and Entrepreneurship Competition and the Peking University 1898 Innovation and Entrepreneurship Competition. The results and feedback are still pending.

Conclusions

So far, we have evolved our business plan four times, making improvements in almost every aspect. We have received acknowledgments from various experts and advanced to the final national competition among 400 business plans. In fact, we have already received numerous offers for investment. We believe that we have made significant progress and possess a feasible business plan.

Risks Assessment and Management

Technical Risks Assessment and Management

• Technical maturity and reliability issues:
  Therefore, in the design of the Curmino system, we conducted extensive research and ultimately chose to combine the bioorthogonal reaction system with the codon expansion technology, and to use the Curli system of ECN bacteria. All three have been widely studied and proven to have good effects. In Professor Liu Tao's laboratory, the bioorthogonal reaction system and codon expansion technology have been deeply studied, establishing a comprehensive system. There are already phase II clinical trials based on the tetrazine-TCO system. This evidence has verified the maturity and reliability of the technology.
• Technical cost and accessibility:
  Currently, most existing biological therapies are problematic due to their high cost and relatively poor accessibility, benefiting a smaller number of people. However, we hope to transcend borders and time zones, challenge the status quo, and strive to develop therapies with greater accessibility for people around the world. Therefore, controlling the cost of the technology and improving its accessibility is very important! In our design, our modification is based on ECN, a widely used E. coli, which is relatively low in price. Moreover, the bacteria of this technology can be prepared in large quantities, suitable for a wide range of people, and not a personalized treatment plan, which greatly reduces the price of the product. In addition, in this experimental design, the molecules used have been deeply studied by us, and we have optimized the synthesis steps, greatly improving their yield.
• Biosafety and ethical issues:
  Synthetic biology may bring biosafety risks, such as accidentally creating harmful organisms or causing unpredictable impacts on the ecosystem. Ethical issues are also an important factor restricting the maturity of these technologies. For example, the application of gene editing in human embryos has sparked widespread ethical controversies and legal issues. In the experimental design, we considered these issues in advance, and we introduced a suicide gene into the engineered bacteria, which will express, causing the engineered bacteria to die automatically when exposed to the environment. In addition, we have also carried out quite a few safety-related activities to ensure biosafety. We have also researched the laws and regulations related to synthetic biology, and in the experimental design, we have considered these laws and regulations to make the experimental design ethical.

Regulatory Risks Assessment and Management

• Currently, the standards for efficacy and safety recognition are unclear:
  We confirm with the legal departments of pharmaceutical companies and regularly update project progress, while also paying attention to policy trends related to probiotic drugs, dynamically monitoring and correcting any related risks at any time.
  Insufficient evidence of strain effects: We have conducted multi-angle and in-depth proof-of-concept work at the wetlab stage and expect to produce scientific articles as endorsement.
• Potential risks such as allergies are not fully disclosed:
  We will carry out sufficient allergy testing and other side effect testing, and provide as detailed an instruction manual as possible to avoid patient harm. At the same time, we will also make clear statements in product promotion and labeling.
• There may be strain contamination issues:
  We have knocked out the ThyA gene of EcN in the wetlab. It lost the ability to autonomously synthesize the essential thymine, thus in the event of leakage into a natural environment lacking thymine, our strain will die quickly, reducing the impact of the strain on the environment.

Team and Talent Risks Assessment and Management

• Key R&D personnel or management may leave, taking away important technical or business resources, affecting the continuity and progress of the project, causing talent loss:
  On the one hand, we focus on the confidentiality of core technology and intellectual property management, on the other hand, we implement a competitive compensation plan for employees to improve employee satisfaction and retain key talents.
• The project may lack specific professional skills during its development, such as clinical trial design, strain iterative cultivation, etc., causing a technical gap and affecting the R&D process:
  On the one hand, we will dynamically monitor key positions and adjust compensation flexibly according to project needs to attract talents; on the other hand, we will establish a continuous employee training and professional development plan for the long term; on the other hand, we consider cooperating with academic institutions or professional consulting firms to fill the skill gap.
• With the growth of the company's employees, there may be poor coordination among various departments, insufficient cooperation among team members, affecting the team's overall execution and innovation ability:
  On the one hand, we have established clear communication channels and cooperation mechanisms to ensure clear division of labor among team members, forming an environment of healthy competition and win-win cooperation, on the other hand, we will regularly hold team-building activities and project progress meetings to ensure full communication among all team members.

Intellectual Property Risks Assessment and Management

Patent Infringement:

We have conducted extensive research on relevant laws and regulations and consulted with intellectual property experts on patent considerations. On the one hand, we aim to strengthen our own patent protection to prevent infringement of Curmino's core patents. On the other hand, we want to avoid infringing on other patents.

Regional Differences in Patent Applications

We have not only researched Chinese intellectual property laws and regulations but also those overseas to avoid situations where differences in laws and regulations lead to patent applications being denied or result in infringement of others' patents.

Educational Significance

Members of the PekingHSC team are not only iGEMers but also students. Throughout the project implementation process, we are eager to explore the boundaries of our interests while completing the project, to realize the exploration of our own values, and to achieve growth in our abilities. At the same time, we also hope that our project can bring help to those around us, allowing them to understand new technologies, trends, and methods.

Self-Education: Most of the members of PekingHSC come from professional backgrounds such as pharmacy, medicine, and biology. Although our professional backgrounds are similar, each person has different interests and career development paths. We make full use of the opportunities for project communication with the outside world, allowing different members to participate in various exchange activities according to their interests. To this end, we seize every opportunity for external communication. We connect with industry leaders to understand market demands, we participate in investment roadshows to promote the transformation of results; we cooperate with multiple universities to innovate and lead development; we attend academic conferences to jointly explore new knowledge of the times... In the communication across different fields of industry, academia, and research, our project is gradually improved, and our members achieve personal growth.

Altruistic Education: During external communication, we found that people's understanding of synthetic biology and bacterial therapy is relatively insufficient, which greatly limits the efficiency of our external communication. Therefore, we hold a variety of popular science activities on university campuses to convey the knowledge of synthetic biology and bacterial therapy to others.

Tumor therapy using engineered bacteria, as a novel treatment strategy, holds promise to address many of the challenges faced by traditional cancer treatments, offering a new perspective on cancer therapy.

However, it is also important to note that bacteria face issues such as host immune responses and genetic instability, presenting significant challenges in terms of safety and clinical trials, especially for pathogenic or conditionally pathogenic chassis bacteria. In the implementation of our project, we have been aware of this issue from an early stage and have attempted to communicate with various sectors of society, hoping to propose effective solutions to pave the way for the successful development of anti-tumor engineered bacteria, explore cutting-edge scientific issues of "safe engineered bacteria," and contribute to the development of synthetic biology industry.

To this end, we have organized the first "International Symposium on Escherichia coli Nissle 1917 security" and, in collaboration with synthetic biology research teams from several domestic universities, released a white paper on the E. coli industry. We hope that through multi-party cooperation and exchange, we can collectively address the safety issues of engineered bacteria.

Our work is not just scientific research, but also a responsibility and mission. Through the iGEM project, we are not only exploring the mysteries of synthetic biology in the laboratory, but also bringing this knowledge out of the campus and into society, allowing more people to understand and recognize the importance and potential of this field.

Our project is not just about winning competitions, but about advancing science and solving real-world problems, such as cancer treatment. With our exploration of engineered bacterial therapy for tumors, we hope to bring new hope to patients and revolutionary changes to the field of medicine.

In this process, we have also become aware of the potential safety issues that synthetic biology might bring. We actively communicate with all sectors of society, organize seminars, and publish white papers, hoping to attract more attention and jointly promote the healthy development of this field.

Our work is interdisciplinary and the result of teamwork. Every team member has grown in this process; we have not only learned knowledge but also learned how to transform knowledge into action and how to communicate and cooperate with different people.