Qian Xueming: MabSpace is an idea generated in half-awake
“On August 17, 1990, I went to Manhattan with US$400 borrowed from my uncle.On September 22, 1997, I joined Amgen and started postdoctoral research.
On January 4, 2013, MabSpace Biosciences officially went into operation.”
Dr. Qian Xueming can describe any detail of his experience without hesitation. The good memory left a deep impression to Xieyi. “An officer of the Admission Office of Columbia University came to China to hold an interview with me. We made an appointment to meet at 5pm at Jing’an Hotel. It was far from Wujiaochang and the bicycle I rode was broken on half way. I got my hands smudged with oil when I repaired the bicycle myself. Fortunately I arrived on time. When the officer signed the letter of admission and gave it to me, my heart beat fast.” When listening to his narration, one can easily be absorbed.
Founder/CEO of MabSpace Biosciences (Suzhou) Co. Ltd.
Dr. Qian created MabSpace Biosciences (Suzhou) Co. Ltd. (MabSpace) in early 2013 and established an immune tolerance barrier based novel antibody development platform and develop the new generation antibody medicines with intellectual property protection. Dr. Qian joined the molecular genetics department of Amgen in 1997 after getting the doctorate at Albany Medical Center to engage in the biological engineering new drug development as a postdoctorate. In 2000, he was promoted as scientist and participated in several antibody and micromolecule new drug development projects. In 2005 Dr. Qian was promoted as chief scientist and led his teams to discover therapeutics for chronic renal failure and obtained multiple global patents. Dr. Qian was Head of R&D of Shenogen Pharma Group from 2010 and 2012 and chaired development of ER-a36 monoclonal antibody and promoted application of Icaritin in primary liver cancer treatment.
“In the postgraduate period, Qian has devoted to study of the brain nervous system growth and published three papers on the study. To the day, the papers have been quoted for more than 1,500 times.”
Dr. Qian believes overtaking must rely on a strong team. In these years, MabSpace has introduced recognized biomedicine talents. Guangliang Greg Pan’s joining enables MabSpace to establish CMC. “Recently there will be a new colleague who has engaged in CMC at Genentech for 19 years. We all have an international perspective and share the same goal of developing the best drugs of China. Of course we are confident in our antibodies.” The growing team gives more confidence to Dr. Qian. “Once the drugs enter the clinical test, we can show effectiveness and safety at indications. Therefore the next year will be very interesting.” He invited Wan Yuntao, a clinical expert, to take charge of the clinical test. He is confident in the new colleague who was his classmate and a “top student” of biophysics at Fudan University. He said he lost the qualification for a recommended student of the most chic discipline biophysics that year, but he fortunately got acquaint with many excellent classmates and some of them are renowned experts of their professions.
After graduation, Dr. Qian went to New York to study neurobiology at Columbia University and started to get interest in pharmaceuticals. After obtaining the doctorate, he joined Amgen for the postdoctorate research for attractions of the big pharmaceutical factory, and the beautiful scenery and warm people of California. “After sending my resume, I received a call from Amgen and I asked ‘how about the future of the postdoctorate at your company?’ He immediately sent me his resume and told me postdoctorate could join Amgen and has a good future. It was hard for me to make a decision because I had two offers, and one was from Harvard. I told him ‘I am not sure to go to your place.” He said, ‘no problem. You could come here to have a look and see our classmates near Los Angeles. It is sunny here.’ I was convinced.” Getting used to indifference and seriousness of New York, Dr. Qian had a good opinion of California’s openness and relaxation. “In the more than two years as a postdoctorate, our team often drove a half hour and climbed over a mountain to have lunch at the beach. It was so comfortable to drink cool beverage and look at the blue sea. When we returned our office at 2 o’clock, our boss has not come back yet.”
“I had a preliminary idea of this company in my mind when I worked at Amgen. It was an idea I conceived in half-awake. It was just an idea.”
In 2000 Dr. Qian became a regular employee of Amgen and was promoted chief scientist five years later and joined an antibody therapeutics project for chronic renal failure. It was the most important five years in Amgen and his career as well. He headed a team of 15 members and engaged in tasks from looking for target to producing antigen, screening antibody and making animal model and to assessing druggability and safety performance. “I need to persuade the department leader to get budget and gain support from partners in and out of the company.” From a scientific researcher to a real project leader, Dr. Qian gained valuable experience. “I learned these knowledge in these five years, from the project initiating to resource mobilization, controlling risks and leading the team. All these experiences can be directly used in my entrepreneurship.” He developed drug candidates and applied for several global patents. After the project was completed, Dr. Qian resigned from Amgen and he knew what he wanted to do.
When working at Amgen, Dr. Qian and his colleagues often made dozens of site-specific mutagenesis on the antigen protein after identifying an antibody and analyzed which mutagenesis could destroy antibody’ capability of binding antigen and applied for a patent to protect important amino acid. Because many antibodies with different binding sites were made, a number of amino acid binding patents have been obtained by Amgen, meaning the path to the same targets has been blocked for later-comers. “Many antibodies of the same target share close sites on epitope and may cause the following consequences: first, many similar antibody therapies on the market, and second, products are vulnerable to limitations of rivals’ patents because the epitope space is narrow.” Before leaving Amgen, Dr. Qian started to consider how to find a new path in the antibody therapeutics.
“It was an idea jumped out when my brain was relaxed,” said Dr. Qian. According to the immune system growth principle, it is hard to produce antibody among the same proteins. To improve capability of producing antibody, we need to apply “unknown alien invaders” to stimulate it. Human being and mice share at least 60% amino acid sequence. If injecting human’s protein into mice, resulting antibody binding sites are normally falling to the 30%-40% different amino acid sequence between human beings and mice. “If breaking tolerance of its own protein, the resulting antibody epitope diversity will be improved, providing advantages of druggability and patent protection. It is the space for MabSpace to enable developers to have sufficient antibody epitope binding space, break away from constraints of rivals and produce drugs with the best effectiveness.”
“We started projects in 2014. We was left behind by the others from the perspective of market access. But we started from the second generation, better than the others in terms of the curative effect. Our PD-L1 antibody is the world’s only targeting humanized antibody with pH-dependent antigen binding properties.”
Dr. Qian returned China in 2010 and served as Senior VP and R&D director of Shenogen Pharma Group. In three years, he made more preclinical tests for the first class new drug Icaritin and recommended liver cancer indications. “After Icaritin entered Phase II clinical test, an important project has been applied and the financing is almost in place, I think it would be too late if I do not start my program.”
With support from angel investors and the government, MabSpace was incorporated in October 2012 in Suzhou.
At the very beginning, MabSpace has no laboratory or animal house, but an empty roughcast house and Qian’s idea. “We designed many polypeptides with computer moulding and proved the immune tolerance barrier breakthrough technology is feasible with outsourcing services and could produce more diversified antibodies of binding epitope than conventional technology. On this basis, we screen antibodies at the best sites.”
Like most startup companies, MabSpace was penny-pinching. Dr. Qian made drawings, selected decoration materials and designed the company Logo by himself. With completion of the laboratory and the animal house, advanced antibody development equipment have been gradually arranged in place. An immune tolerance barrier breakthrough technology based antibody discovery platform has gradually taken shape: it can complete a full range of works, including antibody production, antigen modification and immunization, high throughput screening and purification, in vitro and in vivo functional antibody assessment and antibody engineering optimization. MabSpace started to provide outsourcing services for other biomedicine enterprises to get valuable cash flow.
“Our platform not only produces antibodies with different epitope binding, but also has discovered some targeting PD-L1 antibodies with pH-dependent antigen binding property.” Dr. Qian read a paper on a new technological renovation for the second generation product which reduced the frequency of drug use from biweekly to monthly. This paper happened to hold the same view with Dr. Qian. He determined to produce the second generation antibody with better curative effect, less toxicity, faster onset time and smaller dosage. The antibody with pH-dependent antigen binding property meets the requirements on durability.
However, the huge investment on antibody therapeutics made Qian’s team not to develop it into medicine. “We provide services for other enterprises and earned several million RMB a year. It needs at least US$10 million to develop an antibody project to IND phase.” But should the company serve the others all the time? Dr. Qian was caught in a dilemma. Soon some investors discovered the potential of MabSpace. “If I make investment, will you develop the antibody therapeutics?” Dr. Qian’s team screened a pH-dependent antigen binding antibody with good druggability with a long time and decided to accept financing to proceed. In 2015 MabSpace received a financing of US$15 million from Lilly Asia Ventures.
MabSpace identified the antibody with a long time before receiving investment. If the pH-dependent antigen binding antibody could not obtain a better curative effect on clinical application with a smaller dosage, it is not competitive in the market. Therefore MabSpace has made a lot of additional works to prove performance of the antibody before launching CMC. Comparing with licensed similar products of Genentech and AstraZeneca, pH-dependent antigen binding PD-L1 antibody has a better tumor killing effect with a smaller dosage and a longer inhibition time.
“We are engaging in the clinical test and Round B financing. For investors, we hope they could really understand our medicine and bring resources, better resources from abroad. When we solve the patent issue, I am confident to compete at the international stage.”