Reistone Biopharma: Global Vision from China | Jianghu
In October 2018, JAK1 inhibitor SHR0302 of Hengrui Pharmaceutical was approved by FDA to carry out a phase II clinical study for ulcerative colitis; more than one month later, NMPA also approved the clinical trial application; and in March 2019, Poland Food and Drug Administration also approved the trial. This Sino-US-European international multi-center clinical study had thus entered the global launch and patients enrollment phase. Surprisingly, it was Reistone Biopharma, a young, global innovative biopharmaceutical company headquartered in Zhangjiang, Shanghai that brought this product under investigation to the global market rather than the US and European enterprises. This seemed to have broken the conventional pattern of license-out.
What make Hengrui Pharmaceutical choose to cooperate with a start-up company after the "overseas trip"? What kind of company enable China's R&D products to realize the rapid launching on the international market? With a lot of curiosity,, Pharma DJ met the founding team of Reistone Biopharma in an open office area of Zhangjiang High-tech Park. Although its own office building would be used at the end of May, Reistone Biopharma had promoted the global clinical development projects steadily. This is quite like the early spring of Shanghai, where there is a hint of chill but with unconcealed vitality.
Looking to the global market
Min Wang Irwin, founder of Reistone Biopharma, has more than 25 years of clinical development experience, and served as vice president of clinical development and medical affairs in Bayer in Mainland China and Hong Kong, vice president of medical development of GSK in China, head of clinical development of Takeda in Asia, etc. before establishing this company. However, she was not content with these. When serving as a senior executive in the multinational enterprise, she was always thinking about how to bring local projects to other countries and to become a global pioneer based in China.
Unlike the founders of most biopharmaceutical corporates, Min Wang Irwin was formerly a venture partner at Qiming Venture Capital. This experience allowed her to witness the rapid development of biopharmaceutical industry of China from another perspective and also see the advantages and disadvantages of different enterprise modes. Therefore, she gradually came up with an idea to “make global innovation based on the existing clinical development advantages”.
When talking about the business mode of Reistone Biopharma, Min Irwin said with a gentle tone but her eyes were firm that, “out of consideration of globalization strategy, we did not found Reistone Biopharma by seeking a help from an investment institution.We did not want to be a company only with rights of market development in China.” If license-in has become an established track for innovative pharmaceutical enterprises in China, Reistone Biopharma is trying to create a new mode. This courage to break the existing mode came from the wisdom of decision makers, and the strength of the team.
In 2005, as one of the overseas returnees who returned to China earlier, Min Wang Irwin joined the large multinational biopharmaceutical company, and led the large clinical development team. She deeply felt that, Chinese R&D talents in new drugs were very eager to participate in the global projects, not just limited to Chinese market. Therefore, building a Chinese team with global clinical development strength also became the core value of Reistone Biopharma.
On the basis of such concept, Reistone Biopharma attracted a group of excellent partners. Wu Yihan, chief medical officer, received his Bachelor of Medicine and Doctorate of Medicine degree from Aberdeen University, UK. He once worked in the UK headquarters of GSK, with rich experience in the approval of IND and NDA in the world including China. When he came to China five years ago, the biopharmaceutical industry of China was booming. In his opinion, China has reached a certain level in the basic research, but is still short of R & D personnel with global clinical development experience. Eight years of working experience as physician in the UK allowed him to see the patient demands more clearly.
“Throughout the world, there is a lot of unmet demands for patients suffering from the autoimmune diseases, and the existing drugs fail to realize the effective control of these diseases. we think there is a good prospect in the field of these diseases.” Speaking of the original intention to join Reistone Biopharma, this Chinese Chief Science Officer in Malaysia, having a style of British gentlemen directly said, he was looking forward to bringing the products of China to the world than introducing overseas products into China for clinical research and development.
As a global-oriented R & D enterprise, Reistone Biopharma has built the teams in Shanghai, Beijing, and Boston of the United States. On the day of interview, Cao Haifeng, vice president in charge of registration and external affairs in Beijing, talked about the topic of joining Reistone Biopharma on the phone. In his opinion, the global simultaneous development was not allowed to be realized under China's previous regulatory environment and approval process. The policy reform of CFDA in 2015 promoted the optimization of ecological environment for new drug R & D in China, and made it possible to go global based in China, which was a good opportunity.
Cao Haifeng (the second one from the left), Min Wang Irwin (the fourth one from the left), Wu Yihan (the seventh one from the left), and Lucas, head of Boston team (the first one from the right) in the founder and main management team of Reistone.
“In October of previous year, FDA approved the application for phase II clinical study on SHR0302, and at the end of November of the same year, NMPA also granted the clinical study approval, which was unimaginable in the past. Recently, we initiated the enrollment of patients successively in China and the United States, which was extraordinary progress.” We could feel his excitement on the phone.
For Cao Haifeng who once served as the head of the registration department at GSK China and BI China, his main work was to introduce the overseas products to China for clinical development in leading the large registration teams of multinational companies during the past 20 years. As a pharmaceutical person deeply rooted in China, he always hoped to utilize his own experience in the global clinical development projects, which was more like a feeling.
Taking patient needs as the driving force for innovation
As an industrial leader, Hengrui Pharmaceutical has been working to bring its products under research and development to the global market in recent years, combined with the clinical development experience of Reistone Biopharma team, which makes it possible to develop cooperation for both companies.
In this era of constantly pursing innovation, Min Wang Irwin has a unique view on this. “Of course, innovation makes us excited.However, Reistone Biopharma, as a young company that has just started, hopes to make innovation based on the patient demands, and to identify preferred indications and patients for development. This is our true motivation.”
Compared with Hengrui's ownongoing clinical study on rheumatoid arthritis, Min Wang Irwin is eager for bigger challenges: selection of indications of ulcerative colitis and Crohn's disease. Wu Yihan, Chief Science Officer spoke out his opinion that, “today, there are many products used to treat tumors. In fact, there is a number of patients suffering from the autoimmune diseases throughout the world. These diseases can survive for a long period, and patients need to take medicine for life once being diagnosed. If we can develop more valuable indications through clinical trials of high quality in this field, more patients will be benefited.” Founder Min Irwin believes that, it is precisely the constant breakthroughs in target research that makes innovation in this field more possible. And there is no clearer scientific advancement in some diseases, it is very difficult to drive further innovation.
In the existing pipeline under research and development of Reistone Biopharma, there are also new indications of atopic dermatitis and other autoimmune diseases, in addition to ulcerative colitis and Crohn's disease. Besides, Reistone Biopharma is negotiating cooperation with Hengrui Pharmaceutical and other channels. License-in of SHR0302 from Hengrui is just the first step for Reistone Biopharma. It will cooperate with more companies to bring China's products to the world.
Strategies and challenges for simultaneous development
In most circumstances, it is quite difficult to carry out true, simultaneous development in different countries. Reistone Biopharma has indeed carried out the same trial on SHR0302 in China, America and European countries simultaneously. Min Wang Irwin believes that to realize this, first is to benefit from improvement of China's drug administrative management policy. Cao Haifeng, vice president of registration and external affairs, thinks that the clinical development consists of planning, application and implementation. Each of them is to be optimized for true and simultaneous development. “Policy reform of NMPA is certainly one of them. Meanwhile, we also hope that medical institutions, ethnics committees and Human Genetic Resource Administration Office of China, etc. can quicken the reform.”
Design of clinical development plan is important, and can demonstrates the experience and strength of the team. Wu Yihan said frankly that, this is also why most companies select different clinical trial protocols in China, the United States and Europe, “Even for the same disease, the patients vary in different countries. And basic medications of different countries are completely different. A globally feasible protocol can be designed with global medical system, medication habit and other factors taken into account. More importantly, how to communicate and reach consensus with clinical doctors of the United States and European countries also requires higher level of whole clinical study team.”
Wu Yihan thinks that, the rich experience in multinational pharmaceutical companies, the deep understanding of R&D strategies and the familiarity with international standards constitute the advantages of Reistone Biopharma. “For some earlier projects that I once participated in, even no clinical endpoint was determined for drug trials sometimes. In this case, it is necessary to discuss with FDA about what endpoint is acceptable. During this process, I could know about different ideas of FDA and EU. Therefore, with these experience, Reistone can better bring China's products to the world.”
It costs less than half a year to complete the formal establishment of the team, and approval of SHR0302 by FDA and NMPA for clinical trials. Although the phase I clinical trial is carried out in China, Reistone Biopharma has been approved to carry out the IBD phase II clinical trial of SHR0302 directly in China, the United States and European countries, through its efforts and communication with FDA and NMPA. This rapid advancement just explains the high level of Reistone Biopharma team.
In fact, multinational pharmaceutical companies also have different global development strategies for different products. For phases I, II and III clinical trials, the objectives are different, especially in the phase II, both speed and investigation of drug safety and efficacy need to be considered. “Sometimes, global simultaneous development is beneficial, but may affect the overall speed. The phase II is very crucial.” Min Wang Irwin shared her opinion on development strategies for different clinical R & D stages. “Why it is carried out in China, or why you need to go to the US, and which stage is more suitable? These are problems that we are always thinking.” Min Wang Irwin believes that this way of thinking is related to the experience of the team in the multinational company.
Dr. Min Wang Irwin will preside over the panel discussion on “Chinese Innovations Aiming to Benefit Global Patients” at the annual meeting of Pharma DJ
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Decision and management in global perspective
According to the result analysis of some global clinical trials, improper dose (too high or too low), wrong clinical endpoint, management of concomitant medication, etc. can result in failure of R & D.
Therefore, although Reistone Biopharma selects the IQVIA, a global top CRO company, it does not mean that it can fully rely on IQVIA. Min Wang Irwin attaches great emphasis on the selection of disease fields and management of clinical development projects. In her opinion, even the innovation on indications is very challenging. Two executive directors of Reistone have more than 15 years of clinical operation experience, including Lucas, head of Boston team, who once managed the clinical projects of US Shire, and Huang Qian, head of clinical operation in China, who once managed the global clinical operation of Roche. At present, the part of SHR0302 project in China is implemented by Reistone Biopharma team, and the other parts in other countries are implemented by IQVIA.
When the interview was nearly finished, we went out of the meeting room and came to a public area to talk out the 10-year vision of Reistone Biopharma in this open environment. Min Wang Irwin, who has 25 years of working experience, is familiar with introducing overseas products to China for trials, but not interested in copying the mode of a similar multinational company in China. “I just want to build a global-oriented company based in China. We will not become Pfizer, and will always focus on the area we are good at.”
Starting from cooperation with Hengrui Pharmaceutical, the company has included five indications in the existing R & D pipeline. In addition to known Crohn's disease and ulcerative colitis, the application for clinical trials of the third indication has been submitted to NMPA. When being asked about more details, Min Wang Irwin said with smile, it is temporarily inconvenient to announce. “I hope that, by the end of next year, there will be one phase II clinical project in the existing R & D pipeline that can achieve satisfactory results.”