Cancer is one of the most serious diseases that humans are faced up with today, and the development of cancer is often closely linked to the process of cellular DNA damage.

It is well known that the intracellular genome is challenged by various damage factors from in vitro and in vivo at any time, and if DNA damage is not repaired in time, it can result in malignant outcomes such as cell cycle disruption, apoptosis, and cancer development.

Therefore, how to correctly repair DNA damage and the maintain genomic stability are crucial for cell survival and the prevention of major diseases such as tumors. The study of molecular mechanisms related to this is the core of DNA damage repair biology, which has important theoretical guidance for the diagnosis of tumors and the design of anti-tumor drugs.

Prof. Yu Xiaochun, the founder and chairman of SynRx Therapeutics, has long devoted himself to the research on DNA damage repair mechanisms and cancer development. His academic achievements have had a great impact on the detection and treatment of familial breast cancer, ovarian cancer, pancreatic cancer and leukemia.

SynRx Therapeutics is an innovative R&D company focusing on the development of novel anti-tumor drugs using synthetic lethality approaches. We are currently exploring several first-in-class anti-tumor compounds, and preclinical studies are in progress .

20 years of efforts in DNA damage repair

For the past 20 years, Prof. Yu Xiaochun has been focusing on the study of DNA damage repair mechanisms and cancer development.

"My research area is closely related to cancer treatment. After returning to China, I found that the entrepreneurial environment in China is relatively loose and there are many opportunities. However, due to the relatively short start of drug development for domestic original innovation, there was a generation gap compared to foreign countries, especiallythe United States." Professor Yu Xiaochun recalled.

Prof. Yu Xiaochun received his bachelor's degree in clinical medicine from Beijing Medical University in 1996 and his PhD in cell biology from Kurume University in Japan in 2002, and later pursued his postdoctoral research at Mayo Clinic. In the nine years from 2006 to 2015, he served as assistant professor, associate professor, and full professor in the Department of Internal Medicine in the school of medicine of University of Michigan Medical School, and in 2015, he served as a full professor at Beckman Research Institute of City of Hope until 2020.

Twenty years of dedicated research has brought a lot of harvest. Professor Yu's academic achievements have had a huge impact on the detection and treatment of familial breast cancer, ovarian cancer, pancreatic cancer and leukemia, and have won many awards internationally. Received the 2006 American Association for Ovarian Cancer Research Independent Investigator Award, the 2007 American Association for Cancer Research (AACR) Susan G. Komen Breast Cancer Scholar Award, the 2008 American Cancer Society (ACS) Scholar Award, and the 2010 U.S. Department of Defense Breast Cancer Program Epoch-making Scholar Award, 2014 Leukemia and Lymphoma Society Scholar Award, 2018 Tower Cancer Research Foundation Scholar Award, 2019 Pancreatic Cancer Alliance Translational Medicine Research Award, 2019 Taub Cancer Research Foundation Leukemia Research Award.

At the end of June 2020, Prof. Yu Xiaochun returned to China to take up a full-time position as a long-appointed professor at Westlake University, as well as the associate dean for research in the College of Life Sciences.

After returning to China, while attending some assessment and exchange activities, Prof. Yu Xiaochun saw the ideas of domestic companies on innovative drugs and the current general environment and realized that a change was needed: "I was deeply touched because what domestic companies were researching was actually a generation behind the hot topics of international academical and industrial research . I think we should do something really meaningful and original, instead of following others to be a 'me too'."

Through these review activities, Prof. Yu Xiaochun established contacts with many angel investors, and with their introduction and help, the core team of SynRx Therapeutics took shape.

Focus on "small but capable" innovation research and development, let the professional do professional things

On August 17, 2021, SynRx Therapeutics was officially incorporated and registered. Its R&D headquarters located in the Digital Health Town in Yuhang District, Hangzhou, with a site of nearly 2,000 square meters, containing modern molecular and cell biology laboratories and office space where drug development activities are conducted. A branch office in Zhangjiang, Shanghai was also set up as a base for talents introduction.

"We want to create a 'small but capable' team, where everyone on the team is a top expert in their field, so that the professional can do professional things." Professor Yu said. SynRx Therapeutics has quickly assembled executives from industry and investment with rich practical experience in preclinical drug development, translational medicine research and corporate operations management. Under Prof. Yu's leadership, the team's research results are of great guidance for tumor diagnosis and anti-tumor drug design, especially for early stage cancer detection and late stage cancer treatment.

In November, SynRx Therapeutics's founder team - DNA damage repair and cancer therapy leading innovation team was awarded as the leading innovation and entrepreneurial team in Hangzhou in 2020. Meanwhile, a new R&D team with this team as the core will advance the smooth implementation of SynRx Therapeutics's new drug projects.

According to Professor Yu, DNA damage repair belongs to the field of molecular biology, and the domestic development in this field has not been very long. "Before 2005, there were very few subject groups studying DNA damage repair in China, and it slowly developed during the last 10 years. And foreign countries have a longer history of development in the field of DNA damage repair, and they have done a very good job of translation. The biggest advantage of SynRx Therapeutics is that our team has a deep acknowledgement about this field, along with the hot spots and all the R&D processes in this field."

SynRx Therapeutics focuses on the development of innovative anti-tumor drugs. Currently several projects are in full operation, some of which have been fully optimized on novel compound structures, followed by preclinical studies. In addition, several projects have completed early target validation and are undergoing virtual filtering and laboratory testing of compounds. In addition, the company has established strategic partnerships with a number of CRO platforms with outstanding expertise and great reputation in the industry in the development of clinical compound candidates, production scale-up and process studies prior to IND application, and registration application.

Professor Yu said: "As to a part of the projects, we plan to achieve IND application in around two years, and then we conduct clinical studies in a variety of solid tumor indications guided by biomarkers."

Precision drug development for targeted cancer based on synthetic lethal therapy

According to Professor Yu, DNA damage repair is closely related to the treatment of cancer, especially in advanced stages. "Most of the chemotherapy drugs used in the first line now are DNA damage inducers, most of which kill normal cells and tumor cells indiscriminately. So most frontline chemotherapy has obvious non-specific and side effects, and also the human body can develop drug resistance. Therefore we must look for specific targets with precise indicators for individuals, which is the new direction for the next generation of cancer treatment."

Professor Yu said, "Synthetic lethal is a very interesting direction proposed in the last decade, and the most representative application scenario is DNA damage repair in tumor cells. Because the DNA damage repair mechanism of most tumor cells is defective, we can take full advantage of the defects of tumor cells and target tumor cell-specific or highly expressed targets through the principle of synthetic lethal to reduce the impact on normal cells and obtain sufficient efficacy and safety window."

It is based on the principle of synthetic lethal that SynRx Therapeutics conducts precision drug development targeting cancer.

Synthetic lethal was originally a genetic concept. In 1922, when geneticist Calvin Bridge from Columbia University was studying the model creature Drosophila melanogaster, he first discovered that some combinations of mutations caused lethal, while any single mutation did not cause any damage in Drosophila.

Twenty-four years later, Theodore Dobzhansky, also at Columbia University, coined the term "synthetic lethal" to describe this genetic interaction similar to that of Drosophila. Until now, the definition of synthetic lethal has gone beyond the classical genetics of the time.

Synthetic lethal is a phenomenon in which the simultaneous inhibition of two non-lethal genes leads to cell death. That is, cancer cells with mutations in specific gene A will be more dependent on the pathway of complementary gene B. Upon inhibition of gene B, cancer cells will be killed while normal cells are unaffected, so this complementary gene B can be used as a therapeutic target for the development of new drugs.

synthetic lethal mechanism can be used to indirectly target many tumor-specific mutations, including some of the common oncogenes traditionally referred to as "non-druggable", will greatly expand the drug targets for oncology therapies.

In addition, synthetic lethal has the potential to overcome the problem of drug resistance caused by newly created mutations after conventional targeted therapies, as well as to achieve complementary or synergistic anticancer effects in combination with therapies employing other mechanisms, such as tumor immunotherapy. Synthetic lethal has a promising future for application in drug development to specifically kill cancer cells with defects in DNA damage repair.

"To the development of new drugs for DNA damage repair, the target must be selected particularly accurate. An innovative drug can never be developed if people follow the crowd or drift with the tide." Professor Yu emphasized. "Generally speaking, it takes about 5 to 10 years to develop new anti-cancer drugs, and constant financial support is needed during the process, so the research direction must be correct. With the right direction, the success of the project can be guaranteed."

When it comes to the development vision, Prof. Yu said, "The goal of SynRx Therapeutics is to be a truly innovative biopharmaceutical company.We are in a very early stage, like a baby just learning to walk. But we already have a professional and complementary R&D team with great abilities, which is a very high starting point. I believe that with the relentless efforts of our team, we will be able to build an innovative biopharmaceutical company with international competitiveness, focusing on the next generation of precision targeted therapies for the benefit of oncology patients."