People interviewed in this issue:

Chairman of Yiming Anke Tian Wenzhi

▍ Personal introduction

Dr. Tian Wenzhi is mainly engaged in tumor immunology and anti-tumor antibody drug development research. He is an expert on the “Thousand Talents Program” in Shanghai, an expert in the “100 Talents Program” in Pudong New Area, an adjunct professor at the School of Pharmacy at Fudan University, and is currently the chairman and general manager of Yiming Angke Biomedical Technology (Shanghai) Co., Ltd., and is the company's CEO and chief scientist. Dr. Tian Wenzhi has focused on the development and research of anti-tumor products for decades. He has a deep understanding of tumor biology and tumor immunology. He has published 32 academic papers, cloned 7 new genes, participated in an English monograph, and has 28 authorized patents.

▍ First label

CD47 Targeted Drug Pioneer

▍ Company Profile

Yiming Angke Biomedical Technology (Shanghai) Co., Ltd. was established in China in June 2015. It is a research-oriented biotechnology company dedicated to developing cancer immunotherapy. Yiming Angke is also one of the few biotechnology companies in the world that can make systematic use of innate immunity and adaptive immunity. By using the innate and adaptive immune systems, it overcomes the limitations of current T-cell-based immunotherapy to address the large unmet medical needs of cancer patients.

Main text:

“People must first have dreams, but they can't daydream either.” Tian Wenzheng, founder and chairman of Yiming Angko-B (1541.HK), led the company along a path of dreams and a “thorny path”.

Yiming Angke's most prominent label target, CD47, has yet to be approved for marketing globally, and recently news of major international manufacturers terminating the same target pipeline has spread frequently. However, Yiming Angke is still firmly advancing its CD47 pipeline clinical trial. What are the ambitions and prospects of the company All in CD47? **

In the course of an exclusive interview, a reporter from the Financial Services Association discovered that Tian Wenzhi, called “Dream Catcher” on WeChat, is also very pragmatic. His comparative advantages in the principles and structural design of the company's various target drugs are “like a few facts,” but in the end, he will return to clinical data to support it. Moreover, he revealed that Yiming Angke is also actively communicating overseas licensing cooperation for pipeline products with overseas pharmaceutical companies, hoping to add more cash flow to the company. At the same time, he said that the company is confident that B can be harvested within five years.

|Why All in CD47?

Reporter: Yiming Angke has been considered All in CD47 since its inception. Where did this ambition and confidence come from?

Tian Wenzhi: In terms of personal experience, I studied medicine, chose to do immunology research after work, and later developed antibody drugs at IMClone in the US. In the process, I deepened my understanding and recognition of immunotherapy, and also developed some drugs targeting CD47.

CD47 is a very old target. It is found on red blood cells and is known as a “don't eat me” signal, and tumor cells also escape macrophage surveillance through high expression of CD47, that is, immune escape. CD47 targeted drugs are designed to address unmet clinical needs (low PD-1/PD-L1 antibody response rate), exert the three effects of phagocytosis of tumor cells by activating macrophages, turning original “cold tumors” into “hot tumors,” and inducing more tumor-specific T-cell immune responses. Ultimately, the patient's sensitivity and response rate to PD-1 antibodies was restored.

At the same time, research results have shown that the relationship between CD47 and the prognosis of cancer patients is very clear. The survival rate of cancer patients with high CD47 expression is relatively low. This good correspondence makes us think that CD47 is a good target.

Reporter: Does the company's current pipeline R&D progress meet your expectations when starting a business?

Tian Wenzhi: Established in June 2015, Yiming Angke is the first company to make CD47 in China. Although the progress is now quite high in the world, to be honest, the current R&D progress is still slightly slower than what I expected when starting a business, because our small company has limited resources. Unlike big pharmaceutical companies, we are all building platforms while doing R&D, and moving forward.

Reporter: What do you think about the statement that “the CD47 drug can't carry the third phase”?

Tian Wenzhi: If it's an antibody, it's probably really difficult to carry through phase III. The CD47 antibody itself has its own characteristics, because the antibody's affinity is too high and can cause serious antigen silencing effects. The dose must be increased. The dose is 30 mg per kg of body weight, which means that 70 kg patients need 2.1 grams. This is also the reason Gilead and others recently terminated the CD47 pipeline.

Our dose was 2 mg per kilogram of body weight, and our single drug showed two cases of CR (complete remission).

Reporter: How does Yiming Anke differentiate and solve the problem of excessive affinity?

Tian Wenzhi: What we have developed is not an antibody; it is a genetically engineered fusion protein. After genetic modification, we selected a fragment, then formed a recombinant protein with Fc, and through glycosylation, we finally achieved the goal that the products we are currently developing do not bind to human red blood cells at all. It can block the “don't eat me” signal and activate the “eat me” signal at the same time. Our fusion protein technology has obtained patent authorizations in China, the United States, Japan, and the European Union, creating a technical barrier.

This is why I always mention the concept DBD (Drug-by-Design). It is only possible to design a safe and effective molecule through a deep understanding of the target and full understanding of its associated toxicity and biological activity. Whether the design concept can be clinically validated is critical, because design is one aspect; in reality, it is the other.

|Facing questions, speaking with clinical data

Reporter: With some major international manufacturers discontinuing the CD47 recently, how can you deal with internal and external questions?

Tian Wenzhi: There is no need to talk too much. All innovative drugs have only one condition. They are safe and effective, and rely on clinical data to speak.

At the same time, we actively participated in industry conferences to allow professionals to evaluate clinical data. At the ASCO conference in June this year, we had two phase II clinical data selected as oral reports. We still need more time to provide more clinical data for the industry to recognize us. Currently, many institutions are also collaborating with us on the IMM01 project, including the well-known American City of Hope Research Institute, which does hematoma research. They want to use our IMM01 and PD-L1 antibodies in combination to develop specific lymphoma indications.

Reporter: Are you confident that Yiming Angke's CD47 will take the lead or work better?

Tian Wenzhi: At present, we have strong confidence. We have completed clinical phase II patient enrollment for three types of cancer: IMM01 combined with azacitidine for two leukemias, including myelodysplastic syndrome (MDS) and chronic granulocytic leukemia (CMML); the third indication is IMM01 combined with tirelizumab for classic drug-resistant Hodgkin lymphoma after early PD- (L) 1 treatment.

We have also applied for phase III clinical registration for these three indications. Currently, we have received phase III clinical approval for the classic Hodgkin lymphoma indication, which is in the process of starting phase III.

At the same time, we insist on using data; we have great confidence in these pipelines. More than 300 clinical cases have basically verified the safety and efficacy of the company's drugs. Compared with the relevant pipelines of other companies, Yiming Angke's phase II clinical trial data showed that the objective response rate (ORR) and complete remission rate (CR) were much higher. In the future, it is hoped that the company will become the first company in the world to market a CD47 target drug and make breakthrough progress, thus proving that this target can be developed into a drug.

Reporter: What is the current phase III enrollment status for classic Hodgkin lymphoma?

Tian Wenzhi: At the initial stage, we plan to conduct a mid-term analysis as early as the end of next year. According to the feedback given to us by the CDE, if the mid-term analysis data for phase III clinical trials can reach a certain threshold, we may have the opportunity to apply for approval for listing with conditions, which will greatly speed up the marketing process.

There are also indications for CMML (chronic myelomonocytic leukemia). In China, the mid-term analysis data meets certain standards, and it is possible to apply for conditional approval for listing. Furthermore, the drug was certified as an orphan drug by the US FDA in November of last year. We plan to use Chinese clinical data to directly apply for marketing in the US (the US may need to bridge a small sample), so we are contacting the FDA to hold a pre-IND meeting, hoping to obtain breakthrough therapy certification.

|Actively promote BD cooperation

Reporter: The company's fastest growing pipeline is also expected to be analyzed in the third phase by the end of next year, but the company's multiple pipelines are progressing, and no drugs are on the market yet. What strategies will the company have to deal with potential cash flow pressure?

Tian Wenzhi: The current cash situation on the company's account is quite good, which can steadily support the progress of the company's key clinical projects. At the same time, we are also looking for more financing possibilities. For example, some government funds have a more supportive attitude, and there are also other types of investors. At the same time, we are also actively connecting with bank loans, etc.

For us, CD47 is an indicative targeted drug. The company will focus on phase III clinical trials in combination with PD (L) -1. I think the probability of success is very high because we have solved the most important safety issues CD47 needs to solve.

For other pipelines, we will strategically extend the time and make adjustments to some pipelines. At the same time, we are also working on BD and are actively promoting the transfer of overseas rights for some projects. Currently, there are potential overseas interested parties in discussions.

Reporter: What are the plans for the future commercialization and production capacity of the CD47 phase III clinical project?

Tian Wenzhi: We have already commissioned CDMO to help us produce the three most advanced projects. In terms of commercialization, we are also discussing CSO cooperation with major pharmaceutical companies.

Reporter: What do you think about the current environment of the biomedical industry and the future position of the company?

Tian Wenzhi: Every industry has a learning process, and so does the biomedical industry. The “swarm of bees” was overheated a few years ago, and the next two years were too cold. The factors that were too cold include investors' need to return to rationality, geopolitics, and policy influence.

Currently, I think the industry cycle will basically bottom out until the end of this year at the latest. Specific policies for innovative drugs have already been proposed at the national level, and Beijing and other places have also introduced policies to support innovative drugs. We are very much looking forward to the introduction of support policies in various regions. What we are most concerned about is support for the payment system.

Our starting point is to meet unmet clinical needs. With a solid innovative drug research and development platform, we are confident that we can remove B within 5 years. In the future, we hope to be able to target outstanding companies in the industry such as Bioshinda and Kangfang. Seek to transition from Biotech to Biopharma on the basis of steady development after three to five years.

Reporter: Wang Junxian, Lu Afeng