Stakeholders Analysis

Before commencing this year's human practices, our team believed it was essential to identify who could influence our project. Consequently, we engaged in brainstorming sessions to gather diverse ideas. Considering that our human practices are primarily responsible for the wet lab and entrepreneurship segments, we leaned towards stakeholders related to these two areas when listing our stakeholders.

We first created the initial stakeholder map, following a power-interest two-dimensional diagram template. We prioritized those with high power and significant relevance by placing them in the upper left corner of our map for early contact. We avoided engaging with those in the lower right corner who had low power and relevance. For the remaining stakeholders, we planned to engage with them selectively based on project progress.

However, this map did not effectively reflect the differences between academia and industry. Therefore, we made improvements and created the second-generation stakeholder map. In this map, we specifically listed individuals whom we believed would significantly aid our project.

First-generation stakeholder map

Second-generation stakeholder map

In the map, the darker the color of the listed entities, the more important we consider them. We used straight lines to differentiate groups that we thought would help with entrepreneurship and experimentation. For example, we believe that investors are more crucial for the launch of our project than advice from experts, and expert advice is more important than public input. Thus, investors are in the innermost circle, experts in the middle circle, and the public in the outermost circle. They all belong to the industrial stakeholders, hence on the industry side. We decided to use this new stakeholder map for our human practices.

Of course, since we also worked on the commercial module, we later realized that this map could not satisfy our engagement with commercial stakeholders. So, we removed academic figures and incorporated commercial entities into our map. We also outlined how we could help them and how they could assist us, ensuring that our engagement was of high quality through mutual benefit. Eventually, we completed the commercial version of our stakeholder map.

We believed that devising an effective strategy for engaging with stakeholders was crucial, as it was not appropriate to consult some stakeholders before project completion.

After discussion, we established a cycle: help with experiments - assist in determining effectiveness - seek expert opinions to support effectiveness - consider responsibility - find relevant individuals to ensure effectiveness at this stage - help with experiments.

That is, during the project advancement phase, we first sought professors in the experimental field to gain direction and save time on wet lab exploration, ensuring that our experiments were effective. Once we achieved phased results, we then sought industry leaders or professionals to address any shortcomings in Human care. to ensure our project could be responsible to our stakeholders. Following this approach, we engaged with 4 professors, 1 doctor, 5 companies and related personnel, and 9 team collaborations this year to ensure that our human practices could validate safety, effectiveness, and social responsibility for the overall project (you can see our content in the IHP and entrepreneurship sections).

We will continue our human practices towards this goal and update the stakeholder map to ensure our stakeholders remain current.

Questionnaire Survey

We believe that understanding public opinion is necessary for the development of the project. Public opinion plays a constructive role in curmino's subsequent marketing, product iteration optimization and many other aspects.

Therefore, we designed a questionnaire to collect the public's awareness of bacterial treatment. We found that the public is less aware of bacterial therapies.

At the same time, considering that the relevant population in the medical field is the driver of the market environment and the academic environment of bacteriological therapy, we also collected data on the degree of awareness of bacteriological therapy in the medical field.

Surprisingly, we found that most people, with or without a professional medical education, are less aware of bacterial treatments than we thought.

So while we don't include education as one of our gold Award criteria, in order to reduce the obstacles caused by lack of awareness and habit psychology in the future Curmino product transformation, and to promote the emergence of more products like Curmino, we are determined to promote the popularization of bacterial therapy.(for details, see ihp-education)

Academia: Professor of Bacterial Engineering

Tian Songhai, assistant professor at the School of Pharmaceutical Sciences, Peking University

1. Initial Design: Using T3SS for Drug Secretion

After establishing our approach to use bacteria for cancer treatment, our team discussed how to utilize them to their fullest extent. After brainstorming, we planned to use the Type III Secretion System (T3SS) to secrete drugs to achieve our goal. However, since bacteria have eight secretion systems, we are not sure whether the T3SS system is the most suitable for our idea. After discussion among the team members, we have decided to consult an expert.

2. Professor Tian: Switching to an easier system

We consulted with Professor Songhai Tian for his opinion. Professor Tian affirmed our approach. However, he believes that the T3SS is too complex for us, as the system involves multiple structural components that are not fully understood. He recommended that we should switch to a simpler and more editable secretion mechanism.

3. Expert Consultation: easier to engineer

Following this advice, we adjusted our project design. After a series of investigation, we found another secretion system, Type VIII secretion system (T8SS). Compared to T3SS, T8SS was much easier to engineer. So, in the next phase of our wet lab, we started designing projects to utilize T8SS. This change allowed for greater flexibility and efficiency in our experimental designs.

Academia: Professor of Gene editing

Wei Wensheng, expert in the field of gene editing, Peking University

1. Research and Decision: Controlling Protein Secretion

Subsequently, we wanted to know whether EcN could secrete proteins encoded by Csg. We looked up information about EcN and found that Csg exists in the nucleoid of EcN. Since our project is designed based on both the CsgA and CsgB proteins, we need to make the secretion of CsgA and CsgB proteins controllable. To achieve controlled secretion of CsgA and CsgB proteins, we needed to knock out Csg in the nucleoid of EcN and introduce a plasmid. However, our team lacked prior experience in gene knockout techniques, which made this task challenging. So we decided to seek experts to gain inspiration.

2. Professor Wei: Advice for gene editing

At the Capital Biopharmaceutical Elite Exchange Meeting, we were fortunate to attend a lecture by Professor Wei Wensheng, who introduced the caspase system for gene knockout. Inspired by this, we adopted the caspase technology for our project.

3. Get EcNΔCsg strain

Fortunately, the team members managed to achieve our goal by trying the caspase technology, enabling us to control protein secretion in a desired manner.

Academia: Professor of Type VIII Secretion System

NeelS.Joshi, Associate Professor, Department of Chemistry and Chemical Biology, Northeastern University.

Tian Songhai, assistant professor at the School of Pharmaceutical Sciences, Peking University

1. Initial Failures in Protein Purification

During the purification process of CsgA, we attempted several experiments but met repeated failure, prompting the search for a more effective method. We consulted various literature sources to explore alternative techniques, In the end, we decided to consult a professor in the relevant field.

2. Professor Joshi: More emphasis in Characterization

After reaching out to Professor Joshi for advice. He told us that purifying CsgA is particularly difficult and suggested that we should focus on characterizing the Curli Fiber. He also gave us advice on ways to characterize the Curli Fiber. Thus, a heavier emphasis was put on characterization rather than purification.

email from Professor Joshi

3. Result: Achieve the desired results

Following his suggestion, we characterized Curli Fibers in Congo Red, Cy5 assay, co-localization assay and flow cytometry experiments. As for purification of the protein, we didn't completely give up and tried for several times as the experiments progress.

For more information please refer to wet lab.

Eventually, we successfully purified a higher concentration of the CsgA protein as well as the UAA incorporated version. Excited, we documented our purification method and open-sourced it in the purification section of our wet lab. We look forward to our work on purifying CsgA being helpful to future researchers.

For more information please refer to experiments.

4. Professor Tian: Acknowledgement

After successfully purifying the protein, we paid another visit to Professor Songhai Tian to report on our project. Professor Tian affirmed the progress we had made, and he pointed out that the Type III Secretion System (T3SS) actually injects bacterial effector proteins directly into the host cells, which was not quite in line with our initial team's conception. He advised us to pay more attention to the context and conditions when researching in the future, rather than just focus on the functions. We reflected on our mistakes in literature review and expressed our gratitude for Professor Tian's guidance.

Academia: Professor of Drug Delivery

Wanliang Lu, Professor at the School of Pharmaceutical Sciences, Peking University.

1. Need for Cancer Type Selection

During the characterization process, due to the limited project timeline, we realized the need to focus on a specific cancer type for our next research steps. To this end, we believed it was essential to understand the existing bacterial formulations and administration methods to guide our decision on which cancer to target. Therefore, we decided to seek a professor specializing in pharmacology to answer our questions.

2. Professor Lu's Advice: Choosing Colorectal Cancer

Consequently, we sought advice from Professor Wanliang Lu, who expressed doubts about intravenous injection, considering that the size of the bacteria might clog blood vessels. Intratumoral injection or oral administration would be optimal delivery methods. He also recommended colorectal cancer as our target, given its clinical relevance and the regulatory challenges associated with intravenous injections in China.

3. Determination of cancer types and delivery methods

Based on his advice, we decided to proceed with colorectal cancer and chose oral administration as the most appropriate delivery method.

Academia: Professor of Bacterial Therapy

Liu Zhuang: Professor at the Institute of Nano Science and Technology, Suzhou University

1. Safety Concerns and Design Modifications

After we preliminarily obtained the protein and some background knowledge, we are very concerned about whether our project can ensure safety and efficacy, so as to be responsible to our patients and potential investors. We checked relevant materials, but since there are no products similar to our project on the market in the field of bacterial therapy, we did not get the results we wanted. This requires us to seek experts in the field of bacteria and clinical doctors to answer our doubts. Therefore, the team members decided to first find an expert in the field of bacterial therapy to answer some of our questions.

2. Professor Liu: minding safety problems

We consulted Professor Zhuang Liu, he affirmed our project and also told us:

• Oral administration of tetrazene, a non-natural amino acid, might interfere with the metabolism of normal cells, thereby raising safety concerns. He believes that tet2.0 has already been marketed and has clinical data to support its safety, which we can refer to.
• He discussed strategies for treating colorectal cancer with team members, suggesting that we could try to narrow down the patient population and focus on specific types of colorectal cancer to be more responsible to stakeholders.
• Oral administration can ensure high local bacterial concentration at tumor sites, which is helpful for the treatment of colorectal cancer.
• He proposed the lock-and-key model, which involves immobilizing the drug or other therapeutic molecules on the tumor surface, and then treating the tumor with prodrugs or other effective molecules that are locked behind a reaction with the other tumor surface-bound molecules.
• He believes that our project needs to be simplified because more than three variables may not be safe.

The information provided by Professor Zhuang Liu is extremely important to us. Our team members have referred to Professor Zhuang Liu's suggestions and improved our project accordingly.

3. Project improvement content

3.1. Safety Verification

We have decided to test the impact of the tetrazine amino acid used in our project. We first conducted verification at the bacterial level and found that tetrazine has almost no effect on bacteria. We will subsequently verify the safety of tetrazine in cells and animals.

For more information please refer to safety part.

3.2. Design Improvement

We have adopted Professor Liu Zhuang's lock-and-key model. We have improved the related model and found this approach to be feasible.

However, we have not been able to address all of our questions, such as which specific colorectal cancer our project should focus on, and the extent to which our three variables will impact the project. We have decided to seek out professional doctors later to resolve the remaining doubts we have. We are grateful for the tremendous help Professor Liu Zhuang has provided to our project and for raising issues that our team had not originally considered.

Clinical Hospital: Doctor for Colorectal Cancer

Qi Changsong is an associate chief physician in the Department of Gastrointestinal Oncology at Peking University Cancer Hospital.

1. Addressing residual and new issues: The Need for Expert Guidance

As previously mentioned, we have not been able to resolve all of our questions. In addition, as our project progresses, we have also encountered difficulties in the selection of drugs (such as MMAE, MMAF, DOX, etc.), whether patients can accept bacterial therapy as a treatment option. Although our team has consulted a lot of information, the results have been minimal. Therefore, we decided to seek the help of a professional doctor to resolve the remaining doubts we have.

2. Director Qi: A Better Prodrug Selection

After some effort, we found Director Qi. We had an in-depth exchange with Director Qi, who affirmed our project. Director Qi believes that he has seen many projects that are theoretically feasible but do not yield good results in the lab. He thinks we should pay more attention to the validation of the effects. In addition, he also answered our doubts:

• Regarding the three variables, Director Qi told us that ADCs in clinical use also have three variables, but they do not affect the effectiveness of ADCs. Director Qi believes that we do not need to worry too much about this aspect in the current stage.
• Regarding the specific type of cancer, Director Qi informed us that there is a lack of effective treatment for mid-to-low rectal cancer, and he thinks we should try to tackle this problem and make our contribution to the patients.
• Regarding the selection of drugs, Director Qi mentioned that MMAE is not very effective in clinical practice, and he suggests that we should use DOX.
• Clinical trials related to bacterial therapy have been conducted in the US, and similar efforts are currently underway in China. For cancer patients, as long as there is evidence of effectiveness, they are willing to try such treatments. Therefore, we do not need to be overly concerned about the patients' willingness.

The clinical information provided by Director Qi is considered extremely important to us. We have referred to Director Qi's suggestions and have decided to improve our project accordingly.

3. Project improvements

In response to Director Qi's suggestions, we have decided to switch the drug to DOX. At the same time, we are also diligently gathering information to understand the background knowledge and clinical treatment shortcomings of mid-to-low rectal cancer, striving to make our project more responsible to others.

Collaboration: Jilin University iGEM Teams

1. Collaboration on Ethics and Environmental Concerns

In August, we collaborated with Jilin University's iGEM team to write an ethics white paper. This process highlighted the importance of preventing our engineered bacteria from contaminating the natural environment. We suddenly realized that our current project did not take into account the environment and the willingness of patients, and we decided to make modifications to make it a more responsible project.

2. Ensuring Safety with ThyA Gene Knockout

To address these: After consulting relevant materials, we have decided to make the following improvements:

• We decided to knock out the ThyA gene in the engineered bacteria. This genetic modification ensures that the bacteria can only survive in the tumor micro-environment, eliminating the risk of spreading into natural ecosystems. This precautionary measure was critical for maintaining the ecological safety of our project.
• We have decided to introduce MazF, a toxin protein from the Escherichia coli toxin-antitoxin system, which can specifically cleave ACA sequences in single-stranded RNA. We utilize arabinose to induce the expression of the plasmid carrying the MazF sequence, thereby triggering the programmed cell death of EcN. This ensures that we have a method to clear the engineered bacteria from the patient's body once the patient decides to terminate the treatment.

Conclusion: A Structured Path from Concept to Application

For the experiment: From the initial design phase to solving key challenges in protein purification and gene editing, our project has advanced through expert collaboration and careful refinement. Targeting mid- and low- rectal cancer and optimizing drug delivery methods has brought us closer to developing a viable bacterial therapy. By addressing safety concerns through design adjustments and choosing DOX for clinical trials, we are now well-prepared for the next steps. Furthermore, our commitment to preventing environmental contamination through ThyA gene knockout ensures that our project remains both scientifically innovative and ecologically responsible. We look forward to further validating our approach and advancing this promising therapy.

Lisheng Zhang, doctoral student, Peking university

Background

Our team tried to stimulate the protein-protein interaction between two CsgA. However, in previous work, the residues of our protein was 111, which took us several days to stimulate.

Inspiration

Lisheng Zhang is a doctoral student with a specialization in bioinformatics. He has abundant experience in molecular dynamics simulations. He suggested we can ignore the middle parts of CsgA, only stimulating the interaction between parts of the protein which would greatly shorten our time. He provided some article, in which this method was used.

Implementation

In our subsequent work, we adopted the suggestions of Lisheng Zhang, ignored the middle residues of the protein, which greatly shortened our time.

Zeyu Yan, undergraduate student, NJTECH-CHINA-A

Background

Our team tried one-hot vectors and embedded vectors in the beginning; however the performance of these models could not meet our expectations, thus we communicated with Zeyu Yan to exchange our methods, looking for new solutions.

Inspiration

Zeyu Yan is the student responsible for machine learning in NJTECH-CHINA-A. He inspired us to use pre-trained models for embedding DNA sequences instead of simply using simple one-hot vectors or embedded vectors.

Implementation

He suggested that the lack of performance of our model was likely related to poor encoding and suggested that we use more sophisticated pre-trained models to encode the DNA sequence as a whole to better reflect global features. This inspired our subsequent study.

Siying You, undergraduate student, BNU-China

Background

Our team explored methods to make our dry lab various, Siying You is a member of BNU-China responsible for dry lab. We communicated with them about methods used in their dry lab.

Inspiration

During our communication with Siying You, She introduced that their current work can be divided into three parts: including Ordinary Differential Equations (ODE), Molecular Dynamics, and Machine Learning. We gained inspiration from the exchange on how we could better introduce AI technology in our program.

Implementation

The communication between us can provide us with new inspiration, we exchanged our methods for the model and experience in developing the project, which benefit us a lot.

Ge Wang, undergraduate student, SJTU-BioX-Shanghai

Background

In our previous work, we successfully built a system of ordinary differential equations; however, we found it difficult to solve ordinary differential equations with the tools we had at our disposal.

Inspiration

Ge Wang, a member of SJTU-BIOX SHANGHAI, suggested us trying matplotlib. We also discussed with each other about the methods for building a system of ordinary differential equations. SimBiology, which Ge Wang believed to be useful for constructing such systems, provided us with an inspiration.

Implementation

We tried to use matplotlib to solve the system of ordinary differential equations. We also tried SimBiology in our work, combining the capabilities of machine learning with our own experience. Eventually, we managed to optimize the system of ordinary differential equations and obtained accurate solutions.

Renxiu Song, undergraduate student, JLU-China

Background

At the beginning of the project, our team explored methods to make our dry lab various. Ren Xiusong is the leader of JLU-China, we discussed the basic framework with him.

Inspiration

He explained that the common components involved in dry lab work included Ordinary Differential Equations (ODE), Machine Learning, and Molecular Dynamics. He listed some parts of their project; told us the experiences in other projects.

Implementation

Inspired by this conversation, we then modified our approach to solve the problems we encountered in our current project. The communication with Renxiu Song deepened our understanding of the requirements of dry lab work and provided us with new methods.

Symposium on Synthetic Biology and AI for iGEM

The Dry Lab Conference was jointly organized by several iGEM teams from various universities to discuss common challenges encountered in dry lab experiments and how to address them. This year, our team participated in the conference, where we shared the methods used in our dry lab work and received valuable suggestions from other teams. This conference expanded our knowledge of AI for scientific problems; offered us new approaches for improving the performance of our model.

Overview

In IHP, we always keep in mind that our goal is to obtain the most impartial feedback and suggestions from all stakeholders on our curmino project, in order to clear all potential obstacles in the product transformation process of curmino.

Therefore, we have conducted another brainstorming session and created a business version of the stakeholder analysis map.

Works we have completed

Doctors

• We have obtained relevant suggestions on drug delivery options for curmino from Dr. Qi. (for more information, please refer to IHP-wetlab.)
• We have learned the basic logic of rational drug use from a therapeutic drug management perspective with Mr. Deng Ang.

Investors

We learned how to research the pharmaceutical industry market from a researcher at a well-known public mutual fund.

Drug watch dog

Since our product is still in the development phase, we sought advice from the legal department of a pharmaceutical company to ensure the compliance of your project, receiving affirmation in return.

Other enterprise

• We learned from Xinhua Pharmaceutical how to establish long-term friendly relationships with upstream and downstream enterprises.
• We learned from Jingfeng Pharmaceutical how to expand into multiple businesses later on to grow and strengthen the company.
• We gained an understanding of the factors ESG enterprises need to consider from INTCO Recycling.

Other biomedical executives

• We learned from Mr. Kai Kang of Chuangmo Biology about the common VIC model for biopharmaceutical startups and received his advice on the concept validation of our project.
• We received guidance for the China International College Students Innovation Competition and suggestions on project concept validation from Mr. Ye Qi of Evolution Healthcare.
• We learned from Teacher Xiaoming Zhang how to understand an industry and a company by reading a prospectus.
• We learned from Teacher Ping Tang how to tell a good story through a business plan (BP) and received suggestions for modifications in financial forecasting, market analysis, and other modules.

After communicating with investors, pharmaceutical company executives, and other stakeholders, we believe that patent application is an important part of the project transformation. Therefore, we found experts in the field of patents to inquire about matters related to patent applications.

Patent consultant

We learned about the patent application process and considerations from Ms. Menghuan Xie of TipLab Intellectual Property Strategy and Management Consulting Company.

Given that our product's concept validation is still at the cellular and molecular level, consultations related to Franchisers and Market Regulatory Authorities have not yet been conducted. Similarly, as we are currently unable to provide products to patients, out of concern that the introduction of the curmino product concept might lead them to interrupt or even give up their current treatment plans, we have replaced direct communication with patients with exchanges with doctors.

Key Communications

Conversation with Mr. Kai Kang

Mr. Kai Kang is the executive director of Chuangmo Pharmaceuticals and has overseen the company’s advancement in humanized immune system models, which involve transplanting human immune cells into mice. This innovative approach has successfully reconstructed the human immune system in mice, offering a new experimental method for drug development, tumor immunotherapy, and other related fields.

In preparation for our subsequent animal experiments, we contacted Mr. Kai Kang and introduced our project to him.

He first discussed with us the open mode of startup pharmaceutical companies, suggesting that we understand the VIC model—V represents Venture Capital, I represents Intellectual Property, and C represents Contract Research Organization (CRO). Under this model, biopharmaceutical startups are roughly divided into two categories based on whether they own Intellectual Property (IP). One type of biopharmaceutical startup does not yet own IP. In this case, after the company obtains VC investment, it purchases IP from other research institutions and then cooperates with CROs for research and development. After the project is successful, it profits and exits through market mechanisms (going public or being acquired); CROs can obtain order income and investment returns in the cooperation. Under this, venture capital is the engine and pillar of the entire process, which can attract more funds for the industry, promote the healthy growth of these startups, and encourage the establishment of more startups. In addition, he also suggested that we pay attention to immune activation in the intestines, which can be verified with humanized mice; and verify on various types of cancer, trying intra-tumoral injections.

After our internal discussion, we unanimously agreed that preparing for patent applications first is the most important step for us to subsequently own IP and obtain VC investment. In addition, after the competition cycle ends, we are preparing to conduct verification work for the rectal cancer.

Conversation with Mr. Ang Deng

Mr. Ang Deng is a clinical pharmacist specializing in endocrinology and a specialized pharmacist for standardized cancer pain treatment wards. He serves as a member of the "Beijing Pharmacist Association's Chronic Disease Prevention and Control Pharmaceutical Special Committee," a young member of the "China Medical Education Association's Rational Drug Use Professional Committee," and a member of the "Medicine Safety Committee of the Geriatric Oncology Branch of the Chinese Society of Gerontology and Geriatrics.

In our in-depth conversation with Mr. Ang Deng, we gained valuable insights into rational drug use. He emphasized that the underlying logic of rational drug use is not limited to the drugs themselves but requires the integration of clinical thinking and clinical pharmacy thinking. This means that when pharmacists provide medication advice to patients, they must start from the patient's initial condition and comprehensively consider the patient's cultural background, care conditions, treatment preferences, medical history, and current treatment progress.

Mr. Deng Ang's explanation made us realize that every patient is a unique individual, and their treatment plans should be personalized. By sharing a series of special clinical cases, he vividly demonstrated how to analyze and make decisions based on the specific circumstances of patients in actual work. These cases included in-depth discussions on drug interactions, meticulous considerations of patients' lifestyles, and precise adjustments of drug dosages and administration times. Through these cases, we deeply appreciated the importance of analyzing specific situations and the necessity of flexibly applying pharmaceutical knowledge in clinical practice.

In addition, Mr. Deng Ang also emphasized the need to balance multiple aspects in drug treatment, including legality, rationality, accessibility, efficacy, safety, compliance, and cost-effectiveness. These principles are the cornerstone of clinical drug treatment and the core guidelines for the development of curmino.

Legality refers to the use of drugs that must comply with laws, regulations, and medical standards. Rationality requires that the selection and use of drugs must be based on scientific evidence and the actual situation of the patient. Accessibility emphasizes that drugs should be easy for patients to obtain, both physically and economically. Efficacy means that drugs must be able to achieve the expected therapeutic effects. Safety ensures that the use of drugs does not cause unnecessary harm to patients. Compliance involves whether patients can use drugs correctly according to medical advice. Cost-effectiveness starts from the cost-benefit of drugs, ensuring that patients can afford them economically.

Through this exchange, we are more convinced that the development of curmino must be guided by these principles, continuously optimizing drug treatment plans, and improving patients' treatment experiences and quality of life. We look forward to applying these valuable concepts and practices to our future work, providing patients with higher quality pharmaceutical services.

Conversation with Ms. Mengxin Xie

Mengxin Xie is a partner and the head of the Beijing office of TipLab Intellectual Property Strategy and Management Consulting Company. Attorney Xie's practice areas cover life sciences-related fields such as biopharmaceuticals, food industry, and medical devices. She has over a decade of professional experience in patent application, analysis, investigation, technology transfer, and consulting.

After introducing our project to Ms Xie, she suggested that we go through a series of procedures at the Technology Transfer Office of the Medical Department of Peking University before applying for a patent. Once we have obtained the school's patent transfer authorization, although applying for a patent at the Patent Office involves a lengthy examination process, after we have prepared the relevant materials and submitted them to the Patent Office for preliminary review, we can quickly obtain the patent number without the need for re-examination, and exercise various rights such as technological exchange and market transactions.

After communicating with Ms. Xie, we went to understand the relevant regulations of the school. The entire process is as follows: The person in charge of the scientific and technological achievement proposes the intention of technology transfer and forms a preliminary technology transfer plan. Then, the preliminary plan is submitted to the department for review. After the department's review is passed, the materials will be reported to the Industrial Management Office. The Industrial Management Office will communicate with us to understand the situation of the scientific and technological achievements and potential transferee enterprises, and organize experts to conduct commercialization evaluation when necessary to determine the method of technology transfer.

The approval process varies according to the price of the technology transfer: plans with a value of less than or equal to 4 million yuan are approved by the Industrial Management Office; plans with a value between 4 million yuan and 8 million yuan (inclusive) are reviewed by the Industrial Management Office and then submitted to the Medical Department's Science and Technology Achievement Transformation Work Leading Group for approval; plans with a value exceeding 8 million yuan are reviewed by the Medical Department's Science and Technology Achievement Transformation Work Leading Group and then submitted to the Medical Department's Executive Meeting for approval.

We have estimated the patent for this project to be below 4 million yuan and plan to directly start writing the preliminary plan, which will be reviewed by the department and then transferred to the Industrial Management Office for approval.

Conversation with Acrobiosystems Co.,Ltd

Acrobiosystems Co.,Ltd is a multinational biotechnology company established in 2010. It is a foundational enterprise platform that provides key biological reagent products and solutions for the global biomedicine and health industry.

Given that our wet lab colleagues informed us that the technology can also be used for imaging, we believe that Acrobiosystems Co.,Ltd might become an investor for our project or help us find our investors. Therefore, we attempted to reach out to Acrobiosystems Co.,Ltd for a discussion. Fortunately, Acrobiosystems Co.,Ltd agreed to our request, and we met with the Executive Director of Acrobiosystems Co.,Ltd. Our team members communicated with the Executive Director, who believed that the commercialization of our project was entirely possible.

However, he also reminded us that for patients, especially those with cancer, imaging without treatment might not be sufficiently humane. If our project could enable bacteria to directly secrete relevant therapeutic drugs, it could potentially reduce costs and, due to the bacteria's ability to reproduce, might achieve long-term effects, which aligns well with the FDA's philosophy.

Regarding investors, he regretfully stated that since Acrobiosystems Co.,Ltd is a small enterprise, it is not considering investing in projects related to bacterial treatment or detection at present. He believes that only international pharmaceutical giants would be positioned to invest in the bacterial treatment field.

Lastly, he suggested that if we want to commercialize, our stakeholder map needs to be refined further. We took his advice and attempted to draw a commercial version of our stakeholder map.

Conversation with Mr. Ye Qi

Mr. Ye Qi is the founder of Evolutionary Healthcare. His project focuses on the repair of aberrant miRNA specifically present in tumor cells through plant proteins for broad-spectrum anti-cancer therapy. The preliminary results of his project have been published in international top-tier journals such as Cell, Nature, and Trends in Cell Biology. In 2023, he participated in the China International College Students' Innovation Competition (2023), where a total of 4.21 million projects from 5,296 schools in 151 countries and regions registered to participate, with 17.09 million people signing up. His team stood out and won the national championship, receiving funding from the Ministry of Science and Technology's Disruptive Technological Innovation Project.

We have read numerous related literature and found that despite many professors having published their findings multiple times in top journals, translation remains a challenge.

We are also preparing for the national finals of the China International College Students' Innovation Competition (2024), so the path of Qi Ye's team's achievement transformation is very instructive for us.

During the exchange, we first introduced our project to Mr. Qi in detail. We showcased our latest progress in the field of genetic codon extension technology, which can expand the genetic code, allowing us to develop efficient bioorthogonal reactions using non-natural amino acids. We further elaborated on how to combine these innovative technologies with bacterial therapy, in hopes of enhancing the effectiveness and specificity of the treatment. We believe that through this combination, a completely new strategy for cancer treatment can be provided.

After listening to our report,Mr. Qi highly praised our project, considering it not only innovative but also full of challenges.He pointed out that although our project is very attractive conceptually, it is still in a relatively early stage. To further advance the project, we need to conduct more in-depth research and exploration at the molecular, protein, and cellular levels. Mr. Qi suggested that we carry out some proof-of-concept work to ensure that our research direction is correct and our hypotheses are feasible.

In addition, Mr. Qi also emphasized the importance of patent applications. He believes that cultivating awareness of applying for patents is crucial for pushing innovative therapies from the lab to the clinic. Patents can not only protect our intellectual property rights but also attract more investment and partners for our project.

We have seriously considered Mr. Qi's suggestions and plan to have in-depth discussions with our experimental PI. Our goal is to put the patent application on the agenda as soon as possible to provide the best protection and promotion opportunities for our project. We believe that through close cooperation with the PI, we can ensure that our research results can be effectively transformed and ultimately bring real benefits to patients.

To achieve this goal, we plan to take the following steps

• Collaborate with the experimental PI to determine the best timing and strategy for patent applications.
• Conduct more experiments at the molecular, protein, and cellular levels to verify our concepts and gather strong data support.
• Cooperate with patent attorneys to ensure that our patent applications are comprehensive and competitive.
• Actively seek potential partners and investors to support the development of our project.

We believe that through these efforts, our project will be able to achieve a smooth transition from the lab to the clinic, bringing new hope to the field of cancer treatment.

Key Visits

Jingfeng Pharmaceutical

Jingfeng Pharmaceutical is a company focused on the pharmaceutical industry. Jingfeng Pharmaceutical Group's business scope is extensive, covering the production and operation of the pharmaceutical industry, professional incubators, and other big health industries. Specific businesses include the research and development of generic drugs, preparation production (including oral solid preparations, external semi-solid preparations, and external liquid preparations), raw material synthesis, food additives, medical device production, CMO processing, and intermediate processing. The company also has the certification of a national high-tech enterprise, is a national-level technology business incubator, and is one of the "specialized, refined, and innovative" enterprises in Beijing.

During the visit and study at Jingfeng Pharmaceutical, we gained profound insights, especially in the following key areas of practical experience:

Generic Drug Development and Market Demand Alignment: We learned how Jingfeng Pharmaceutical identifies patient needs through precise market research and data analysis, and transforms these needs into specific directions for generic drug development.

Quality and Compliance in Dosage Form Production: Jingfeng Pharmaceutical demonstrated how they implement strict quality control measures in the dosage form production process and ensure that the entire production process complies with national and international pharmaceutical industry standards. These practices are an important reference for us, especially as we strive to improve product quality and ensure compliance.

Advantage Utilization as a High-Tech Enterprise: We understood how Jingfeng Pharmaceutical leverages its status as a high-tech enterprise to obtain policy support, funding, and technology development resources, thereby promoting business diversification and innovation in the pharmaceutical industry. This strategy encourages us to explore how to more effectively use policy advantages to accelerate our Research and Development (R&D) and business expansion.

Through this exchange, we recognized that continuous technological innovation, strict quality control, flexible market strategies, and efficient production capabilities are key to success in the pharmaceutical industry. We plan to apply these experiences to our R&D and production practices to improve our market competitiveness and customer satisfaction.

Xinhua Medicine

Xinhua Medicine is the first chemical synthetic pharmaceutical enterprise in New China. Xinhua Medicine is an important production and export base of antipyretic and analgesic drugs in the world. The company has 26 market share first or exclusive varieties such as aspirin, ibuprofen and levodopa, with annual exports of nearly 400 million US dollars, and has established long-term strategic cooperative relations with more than 200 well-known multinational companies such as Roche, Bayer and Norligo.

After visiting Xinhua Pharmaceutical, we deeply appreciated how this company has cultivated its position in the pharmaceutical industry over the years, establishing a strong market presence and brand influence. Furthermore, Xinhua Pharmaceutical's investment and achievements in the research and development of innovative drugs demonstrate its strong R&D capabilities and profound understanding of the industry's development. The company's R&D projects are diverse, covering various fields including cardiovascular and cerebrovascular drugs, antipyretics and analgesics, digestive system drugs, and have made significant progress in the development of Class I new drugs. Xinhua Pharmaceutical places great emphasis on R&D, with the continuous growth of R&D investment and the introduction and cultivation of R&D talent, as well as innovative organizational and systemic arrangements, which are the best footnotes behind the praise. The company meets market demands and promotes continuous development through constant technological innovation and product research and development.

From this, we realized the importance of innovative drug development. Therefore, we are determined to focus the allocation of funds on the R&D of iterative products (for details, see entrepreneurship-funds and risks).

At the same time, we understood the importance of connecting and cooperating with international companies and are actively practicing this, such as participating in the following HICOOL Summit.

INTCO

INTCO is a high-tech manufacturer of resource recycling and regeneration, mainly engaged in the recycling, regeneration, and utilization of renewable plastics. It has innovatively opened up the entire industry chain of plastic recycling and reuse, perfectly combining plastic recycling and regeneration with the application of fashion consumer goods.

After visiting INTCO Recycling, we had a deeper understanding of the factors that Environmental, Social, and Governance (ESG) enterprises need to consider. ESG enterprises need to take a comprehensive approach to environmental protection, social responsibility, and corporate governance. In terms of environmental protection, companies need to take effective measures to reduce the impact of their production processes on the environment; in terms of social responsibility, companies need to pay attention to the impact of their products on society and actively participate in social welfare activities; in terms of corporate governance, companies need to establish a sound governance structure to ensure the transparency and efficiency of their operations.

By learning from INTCO Recycling's ESG development model, we have made the following efforts:

In environmental protection, we have knocked out the ThyA gene of EcN. It loses the ability to autonomously synthesize the essential thymine, thus when leaked into the natural environment lacking thymine, our strain will die quickly, reducing the impact of the strain on the environment.

In terms of social responsibility, we have placed altruistic education in an important position.

In corporate governance, we have formed a dynamic and diverse team (for more informatioon, please refer to entrepreneurship-project team).

HICOOL

HICOOL is China's largest innovation and entrepreneurship event. In 2024, HICOOL has organized 85 high-profile roadshows globally, reaching over 55,000 entrepreneurs worldwide. Over the past five years, HICOOL has given birth to 16 unicorn enterprises and 127 specialized innovative companies, with award-winning projects securing more than 36.3 billion yuan in new financing after the competition, continuously promoting the development of new quality productive forces.

We were invited to attend the summit. In the summit, we paid special attention to the current projects in the life sciences field. During this time, we were particularly inspired by Ms. Haoxuan Tong 's Zhiyuan Newsage Company, which is mainly engaged in the rare diabetes AI self-replicating mRNA vaccine project. The project focuses particularly on clinical feedback, emphasizing the protection rate for patients.

Hence, we tried to understand the needs of the clinical phase from all angles before our project enters the pre-clinical stage. Therefore, we sought guidance from Director Changsong Qi of the Peking University Cancer Hospital for our project.For more information, please refer to IHP-wetlab. However, considering the psychological aspect of patients, we temporarily abandoned the plan to communicate with patients.