Medicilon Interview with Dr. Wenbo Zhou | Focusing on difficult-to-drug targets, three INDs have bee

The interaction between drugs and targets is the basis of drug design.  Scientists have discovered more than 4,000 disease-related targets, but 85% of them are "difficult-to-drug targets", making them the most difficult frontier to conquer in the pharmaceutical field.

At present, outstanding scientists around the world are devoted to conquering these "difficult drug targets".  Wenbo Zhou, a doctor of medicinal chemistry at East China Normal University, is one of them.  Dr. Zhou has been engaged in the research and development of difficult-to-drug target drugs for more than 10 years.  Among them, the drug development targeting the difficult-to-drug target STAT3 was published in the journals CLIN CANCER RES and J MED CHEM as the first author or corresponding author.  He has received funding from the National Natural Science Foundation of China and has been selected into the National Innovation and Entrepreneurship Outstanding Postdoctoral Fellows, Shanghai Science and Technology Youth 35 and other talent programs.

In 2020, Dr. Wenbo Zhou and his mentor Professor Mingyao Liu founded Yuyao Biotech, utilizing the advanced undruggable drug development platform and AI drug-assisted development platform to challenge the dilemma of difficult-to-drug targets.  It is gratifying that recently, the clinical trial of YY201, the world's first STAT3 small molecule inhibitor by Yuyao Biotech, has been officially approved by the US FDA.  This is the third IND approval issued by Yuyao Biotech in the three years since its establishment.  In addition, Yuyao Biotech was selected as the 2023 "Angel Fund Outstanding Project Eagle Enterprise".

Conquering difficult-to-drug targets cannot be achieved in a day. How does Yuyao Biotech make difficult-to-drug targets possible through AI empowerment?  What challenges is Yuyao Biotech currently facing in the field of difficult-to-drug targets?  Why did Yuyao Biotech obtain three IND approvals in three years and deploy nearly 10 "First-in-Class" R&D pipelines?  What milestones are expected for Yuyao Biotech in the next few years?  With these questions, Medicilon conducted an exclusive interview with Dr. Wenbo Zhou, the founder of Yuyao Biotech.

Q1

Medicilon: The Investigational New Drug Application (IND) of YY201 has been officially approved by the US FDA to conduct Phase I clinical research on malignant hematological tumors.  What milestone significance does it have for Yuyao Biotech?

Dr. Zhou: YY201 is an original innovative drug that Yuyao Biotech has completely independent intellectual property rights.  As the company's first US FDA clinical trial approval, it fully demonstrates the FDA's recognition of Yuyao Biotech's preclinical research capabilities and early clinical research plans.  It is an important step for Yuyao Biotech to move towards globalization development.  In addition, the approval of Y201 also provides a new treatment option for cancer patients, and is expected to provide patients with an effective treatment plan after rigorous clinical research.

Q2

Medicilon: YY201 is one of Yuyao Biotech’s core product pipelines. What are the key challenges currently to realize the full potential of YY201?

Dr. Zhou: Our research and development has always been patient-centered, so the biggest challenge is whether YY201 can truly benefit patients in clinical practice.  In preclinical studies, YY201 has shown good therapeutic effects on various tumors such as pancreatic cancer, non-small cell lung cancer, breast cancer, acute myeloid leukemia, and anaplastic large cell lymphoma.  However, this needs to be further verified in clinical trials.  On this basis, another challenge is how to identify patients who can benefit from YY201 treatment.  In order to establish a solid foundation for achieving the ultimate goal of benefiting patients, we will fully communicate with researchers in clinical trials, combine preliminary mechanism and biomarker research, and complete the exploration of the efficacy of YY201 in specific patient groups on the basis of effectively protecting the rights and interests of subjects.

Q3

Medicilon: What expectations does Yuyao Biotech have for the future performance of this pipeline?  In terms of disease treatment and immune regulation, where might it lead to developments in the field?

Dr. Zhou: For this pipeline, our primary goal is to actively advance in multiple oncology indications for which we have sufficient preclinical data, including acute myeloid leukemia.  At the same time, we are also actively exploring the key role of STAT3 in other indications besides tumors.  As its upstream, JAK inhibitors have been successful, but they also have toxicity that cannot be ignored. The important reason is the non-selective inhibition of the STAT family.  YY201 is a highly selective STAT3 inhibitor with controllable side effects and the potential to expand into autoimmune diseases beyond tumors.  At the same time, based on years of research on the functions and mechanisms of the STAT family, we are also developing STAT3 monophosphate and other STAT family selective inhibitors, and exploring their potential value in various types of diseases.

�™Yuyao Biotech R&D Laboratory

Q4

Medicilon: YY201 is the first nanomolar STAT3 inhibitor discovered and developed by Yuyao Biotech with the help of AI technology.  In your R&D process, how has AI technology changed traditional drug development methods?

Dr. Zhou: Traditional drug research and development often requires a lot of time and resources. Computer and AI technology are subverting the traditional drug research and development.  Ten years ago, we collaborated with computer scientists to use CADD technology to simulate the STAT3 protein-compound interaction to help researchers understand the mechanism of action between drug molecules and protein targets and optimize the molecular structure.  With the continuous maturity of generative AI technology in recent years, drug research and development has entered a new stage.  Generative AI can not only process massive amounts of drug property data, but also automatically generate compounds with potential therapeutic effects, predict the activity, toxicity and other properties of molecules, provide medicinal chemists with more scientific and reasonable suggestions, and discover potential drugs that may have been ignored in the past.

Q5

Medicilon: Regarding the development of AI in the field of drug research and development, in which areas do you predict that we will see more innovation and progress?  What advice would you give to other new drug developers who are considering introducing AI technology?

Dr. Zhou: In the future, we expect to see more AI innovation and advancements in drug discovery and development.  With its rapid learning ability and high-speed information processing capabilities, AI is expected to promote more efficient drug design and optimization, and improve the speed and accuracy of new drug discovery by predicting intermolecular interactions.  Secondly, the advantages of AI in image analysis and bioinformatics can be applied in disease diagnosis and treatment, providing more accurate and earlier disease diagnosis, and more support for the formulation of personalized treatment plans.

Q6

Medicilon: In addition to YY201, what other R&D pipelines does Yuyao Biotech currently have and how is the progress?

Dr. Zhou: In addition to YY201, YY001, another clinical research drug of Yuyao Biotechnology, is an EP4-targeted antagonist and is expected to launch Phase 2 clinical studies by the end of the year.  In addition, we currently have three blockbuster super molecular glue products including YY301, YY401 and YY501.  At present, PCC has been confirmed or it has entered the IND application stage, and clinical research is expected to be launched next year.  In addition to the above anti-tumor drugs, we have also laid out a track for chronic diseases such as osteoarthritis, and looks forward to providing patients with more urgently needed and effective treatment options in the future.

Q7

Medicilon: Only three years after its establishment, Yuyao Biotech has applied for more than 20 invention patents and has deployed nearly 10 "First-in-Class" R&D pipelines. Can you share your experience of such efficient advancement?

Dr. Zhou: First of all, thanks to our very strong scientific research team, which brings together many cutting-edge talents in the fields of artificial intelligence, chemical design and synthesis, new drug screening and evaluation, pharmacotoxicology and safety evaluation.  The team has rich experience in drug development and jointly promoted the research and development of the project.  On the other hand, Yuyao Biotechnology has also carried out "industry-university-research-drug" integrated collaboration research with many top domestic universities and scientific research institutions such as East China Normal University, Hunan University, the First Affiliated Hospital of Zhejiang University, and Sun Yat-sen University Cancer Center.   This greatly improves the R&D and transformation efficiency.

Q8

Medicilon: Yuyao Biotech's current product pipeline covers multiple First-in-Class targets such as EP4, STAT3, and Pan-Ras. It can be said that it specializes in "hard bones".  What makes you persistent in breaking through undruggable targets?

Dr. Zhou: We are a team of scientists starting a business. Our goal in doing research is CNS. When we start a business, of course we want to make products that change the world. The spirit of scientific innovation has always been written in our genes.  The reason for choosing these targets can only be said to be that we have been prepared for it. We have been doing basic research on these difficult-to-drug targets for more than 10 years.  If we don't conquer it, it will be difficult for others to do it, so many of our pipelines are unique in the world.  These "hard bones" seem to be exactly what China's Biotech needs today.

A corner of Yuyao Biotech Office

Q9

Medicilon: What is the biggest challenge you and your team have encountered since starting your business?

Dr. Zhou: Yuyao Biotech is a team of scientists and entrepreneurs. When it was first established, everyone had great doubts about whether we could make a drug since we lacked industrialization experience.  However, after two years of development, we have several globally innovative products that have entered the clinical stage. We started from scratch for these products, overcame many difficulties, successfully obtained clinical approvals in China and the United States, and conducted clinical studies.  So from now on, the spirit of scientists dedicated to originality and painstaking research is actually a valuable asset to our company.

Q10

Medicilon: The company is still in its early stages. What are your expectations for the growth of Yuyao Biotech?  What kind of company do you hope Yuyao Biotech will be?

Dr. Zhou: With a strong team and innovative product pipeline, Yuyao Biotech will surely grow into a global innovative pharmaceutical company.  In the future, we hope to continue to be innovative, achieve more breakthroughs from zero to one, transform scientific results into new drugs that treat diseases and save lives, and provide patients with better treatment options.

Q11

Medicilon: What do you consider your leadership style to be?  Is there a particular leader or leadership style that has influenced you?  Are there any characteristics that you believe are necessary as a leader?

Dr. Zhou: Let’s not talk about leadership. Our senior executives and core colleagues are all business partners. They don’t care about their position or short-term interests, and they are willing to grow with the company.  Our style is to respect professionalism and stimulate innovative vitality, and let more young people take the lead. These are also things that I think are very important in the management process.

Q12

Medicilon: The team of Yuyao Biotech is relatively young. How do you establish and motivate the team? Do you have any special methods or ideas for team management?

Dr. Zhou: Although Yuyao Biotech is a young team, it has a pioneering scientist spirit and industrialization experience accumulated from multiple projects.  Our creative team are all teachers and classmates during their doctoral studies. We all have a common mission and vision, and we hope that our scientific research results can be transformed into innovative drugs that benefit human health.  The entire company is united, self-motivated, shares risks and results, and pursues our dream of new drugs together.

About Yuyao Biotechnology

Yuyao Biotechnology is a new drug research and development enterprise empowered by AI, led by innovation, and focusing on new technologies and new targets.  The company has three world-class new drug research and development platforms and multiple independent original product pipelines, and the core products are currently undergoing clinical research registration.  The product pipeline, YY001, targets the tumor immune microenvironment to treat PD-1 antibody-sensitive and insensitive advanced solid tumors, is about to start Phase 2 clinical research and has the potential to become the world's best immune microenvironment antagonist.  The product YY201 is the world's first transcription factor inhibitor, which is about to start phase 1 clinical research in China and the United States, and other product pipelines will soon enter clinical trials in the future.  The company has applied for more than 20 invention patents and has entered Europe, the United States, Japan, Canada, and Australia through PCT international applications.

The company currently has more than 50 employees with doctorate and master degrees, more than 5,000 square meters of R&D and office space in Minhang District, Shanghai, and has completed hundreds of millions of RMB in investment in professional institutions.  The company has won the National Excellence Award in the Disruptive Technology Innovation Competition of the Ministry of Science and Technology, National Gold Medal of the Youth League Central Committee’s “Creating Youth” Chinese Youth Innovation and Entrepreneurship Competition and honors include the National Gold Medal in the First Postdoctoral Innovation and Entrepreneurship Competition of the Ministry of Human Resources and Social Security and the National Silver Medal in the “Internet +” College Student Innovation and Entrepreneurship Competition of the Ministry of Education.