October 26th, 2019, Boston, the world’s renowned center for education and innovation in the global medical field, welcomed Sino-American Pharmaceutical Professionals Association (SAPA)’s New England Chapter (SAPA-NE) members, world-renowned leaders and regulators to join a full day 22nd SAPA-NE scientific symposium “Leap Forward to Cure” at the Mark and Lisa Schwartz Auditorium, Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge.

More than 200 SAPA-NE members and friends gathered to listen to 10 invited speakers, representing academic institutions, industry leaders and Regulatory agency. The conference was opened with remarks from Dr. Qiying Hu, the SAPA-NE President. Dr. Hu shared the vision and mission of SAPA-NE, the incredible progress of this community, as well as its contribution to the success of the biotech industry in the New England area.

The morning session featured multiple lectures from academic, industry, and regulatory leaders, who shared their views on the development of gene therapy to address unmet medical needs. The keynote speech was given by Dr. Guangping Gao, Professor and Director of Horae Gene Therapy Center at UMass Medical School, cofounder of Voyager Therapeutics, and the current President of American Society of Gene and Cell Therapy. Dr. Gao, introduced the milestones in the development of gene therapy, shared recent progress from his laboratory and collaborators on recombinant adeno-associated virus (AAV) gene therapy vector research, and its application on developing a potential therapy for Canavan’s disease. Dr. Ricardo Brau, Managing Director at L.E.K. Consulting, discussed gene therapy from the commercial and business opportunity perspectives. Interesting business topics, including the comparison between curative gene therapy versus traditional chronic therapy in terms of innovative commercial models and company pipeline management were discussed. Opportunities and challenges of the current gene therapy research and development (e.g. limitations of current process development of gene therapy and CMC management at expedited clinical-trial design) were also discussed and valuable viewpoints were shared. From regulatory side, Dr. Ke Liu, Associate Director for Cell and Gene Therapy, Oncology Center of Excellence & Chief of Oncology Branch at FDA, delivered an exciting presentation on his perspectives of preclinical and clinical considerations in developing gene therapy. This is followed by a presentation delivered by Dr. Nripen Singh, Director of Biopharmaceutical Development at Voyager Therapeutics, discussing the AAV platform development for the process developments, process characterization, unit operations during CMC of gene therapy products at Voyager.

Dr. Qiying Hu, Prof. Guangoing Gao and Dr. Jason Jingxin Zhang.

Dr. Ricardo Brau

Dr. Ke Liu

Dr. Nripen Singh

Questions and Discussion

Speakers and Organizing Committees

The beautiful fall day was perfect for many old and new friends to enjoy the sunshine and lunch table discussion in the courtyard of Technology Square. The afternoon session started by Dr. Hans G. Klingemann, Vice President of Research & Development from NantKwest. Dr. Hans reported the positive results and progress in its NK cell pipeline programs for the treatment of cancer. NantKwest is an innovative clinical-stage immunotherapy company focused on harnessing the power of the innate immune system by using the natural killer cell to treat cancer, infectious diseases and inflammatory diseases. Dr. Hans shared the progress and promise of NK cell based platforms that have been bioengineered to incorporate chimeric antigen receptors (CARs) and antibody receptors to potentially further optimize targeting and potency for the disease treatment. Dr. Jeffrey Palmer, Senior Director of Pfizer shared his perspectives on the clinical trial and FDA approval landscape of gene therapy. Currently, Pfizer is focused on gene therapy treatments for diseases that have single-gene alterations. Their approach is to use recombinant adeno-associated virus (rAAV) that are designed to deliver treatment effectively to the targeted tissue. Dr. Jeffrey Palmer introduced FDA's efforts to advance the development of Gene Therapy through accelerated approval and other programs. He used case studies from Pfizer, such as hemophilia B and Duchenne muscular dystrophy (DMD) gene therapy programs to illustrate how gene therapy clinical trials were designed to meet the challenges of 1) small sample sizes; 2) fewer opportunities to pause and answer questions in an informed way; 3) some indications have no established registrational endpoints. Dr. Alasdair Milton, Vice President at Parthenon-EY discussed the commercial model perspectives of gene therapy. Dr. Alasdair Milton explored how companies can effectively deploy the capital to re-shape their gene therapy portfolios in order to take advantage of this ‘innovation surge.’ Specifically, Dr. Alasdair Milton used Spark Therapeutics as an example to demonstrate how the company has been doing a good job in improving manufacturing as well as building a patient-centric pharma-patient relationship by establishing a specialized medical sciences liaison team. One of the biggest challenges for pharma when developing gene therapy programs is to accurately document the treatment durability. Since patients tend not to go back to doctors for follow-ups after treated by gene therapy. So building a strong patient-pharma relationship is critical for treatment durability documentation.

Drs. Qiying Hu, Hans G, Klinggemann and Jason Jingxin Zhang

Dr. Jerrery Palmer

Dr. Alasdair Milton

After the coffee break and networking, everyone was reenergized to enjoy the last session, which focused on the application of gene therapy for rare diseases and cancers. Dr. Catherine O’Riordan, scientific director of gene therapy in rare & neurologic diseases at SANOFI, first discussed the significant progress of AAV gene therapy for treating many rare genetic diseases. From preclinical, clinical, regulatory, and manufacturing perspectives, the roadmap for AAV gene therapy are maturing. Many novel and innovative approaches are on the horizon using AAV as a delivery vehicle. Then, Dr. Jingsong Cao, principal scientist working in rare and metabolic diseases at Moderna, shared exciting data using mRNA therapy for rare metabolic diseases. Moderna, achieved the biggest biotech IPO in the end of 2018, uses mRNA, the software of life, to spur the body to produce its own therapeutic proteins, essentially creating a drug factory inside of the patient. Dr. Cao shared intriguing preclinical data on treating glycogen storage disease type 1a using Moderna mRNA technology to produce Glucose-6-phosphatase by host mouse liver. The last speaker, Dr. Frank Slack, the Shields Warren Mallinckrodt Professor and Director of the Institute for RNA Medicine at Harvard Medical School, shared his research using microRNA to treat cancers. From precision medicine to immunotherapy, microRNA shows the potential as a novel therapeutic strategy for cancer patients.

We are witnessing a surge of cell and gene therapy products entering early development, evidenced by a large upswing in the number of investigational new drug (IND) applications. Based on this activity, we anticipate that the number of product approvals for cell and gene therapies will grow in the coming years, reflecting significant scientific advancement and the clinical promise of these new innovations.

Dr. Catherine O’Riordan

Dr. Jingsong Cao

Prof. Frank J Slack

Dr Mangeng Cheng

“….We anticipate that by 2020 we will be receiving more than 200 INDs per year, building upon our total of more than 800 active cell-based or directly administered gene therapy INDs currently on file with the FDA. And by 2025, we predict that the FDA will be approving 10 to 20 cell and gene therapy products a year based on an assessment of the current pipeline and the clinical success rates of these products….” A joint statement released by Commissioner Scott Gottlieb and CBER Director Peter Marks on Jan 15th 2019.

The success of the symposium would not be possible without the support of organizing committee members’ tireless effort, many volunteers’ commitment, and vendors and sponsors’ support. Appreciation goes to everyone who made this symposium a success, especially to our Chairs of the symposium, Dr. James Cao, Dr. Lin Lin, Ms Joyce Chen and Dr. Jason Jingxin Zhang, for organizing such a quality scientific event.

SAPA- NE continues our mission to inspire scientific exchange, foster collaboration and dialogues among discovery research, development and regulatory to ultimately deliver to patients of safe and cost-effective treatment for unmet medical needs. This dialogue will continue as the SAPA-NE 2020 annual conference theme “Developing and Delivering the Transformative Medicines for Unmet Medical Needs”, announced by our president-elect Dr. Mangeng Cheng. On behalf of the organizing committee, we all look forward to seeing you at the 22nd SAPA-NE Annual Conference, Boston Marriott Cambridge (50 Broadway, Cambridge, MA) on June 13th, 2020!

Writer: Min Zhu, Ziqing Qian, Xiangmin LV, Kai Zhang

Reviewer: Huijuan Li

Photographer: Dong Yang

秋高气爽波城22nd SAPA-NE 科学研讨会

第三届基因疗法研讨会

2019年10月26日， 这姹紫嫣红的金秋时节，全球医药领域教育、研发、创新的圣地---波士顿迎来了新英格兰美中医药开发协会（SAPA-NE）火热的第22届科学研讨会， SAPA-NE会员、医药研发精英、世界名企领袖，美国药监局代表和广大科研人员等专业人士欢聚在位于剑桥中心的Kendal Square Mark and Lisa Schwartz Auditorium, Ragon Institute of MGH, MIT and Harvard，聆听来自高等学府、全球知名药企、科技创新新锐的10位知名科学家及药物研发领袖的精彩演讲。本次研讨会吸引了200多位来自波士顿地区各大药企、初创公司、著名高校等高层次科研人员参会，人满爆棚、异常火热、所有入场票全部售罄。会议演讲精彩、讨论热烈， 发展进程令人振奋！

超过200位SAPA-NE成员和朋友, 听取了代表学术机构，行业领导者和监管机构的10位受邀演讲者。会议开幕，SAPA-NE主席Qiying Hu博士致辞。胡博士分享了SAPA-NE的宗旨和使命，以及SAPA-NE对新英格兰地区生物技术产业成功的贡献。

上午的会议上有来自学术界，工业界和监管机构领导人的演讲，他们就基因疗法的发展以如何解决未满足的医疗需求分享了他们的观点，主题演讲由美国麻州大学医学院Horae基因治疗中心教授，主任，Voyager共同创始人，现任美国基因与细胞治疗学会主席Guangping Gao博士作了演讲。高博士介绍了基因疗法的发展里程碑，分享了他的实验室和合作者在重组腺相关病毒（AAV）基因疗法载体研究方面的最新进展，以及在开发Canavan病潜在疗法方面的应用。 L.E.K.董事总经理Ricardo Brau博士，从商业机会的角度讨论了基因疗法。 对创新商业模型和公司渠道管理方面就基因治疗与传统慢性治疗作了比较， 还讨论了当前基因治疗研究和开发的机遇和挑战（例如，基因治疗当前过程的局限性以及在快速临床试验设计中对CMC管理的局限性）。在监管方面，来自FDA细胞和基因治疗副主任兼， 肿瘤中心主任Ke Liu博士就他在开发基因治疗中的临床前和临床考虑的观点发表了精彩的演讲。随后是Voyager Therapeutics生物制药开发总监Nripen Singh博士的演讲，讨论了Voyager在基因治疗产品CMC过程中用于过程开发，过程表征和单元操作的AAV平台开发。

Dr. Qiying Hu, Prof. Guangoing Gao and Dr. Jason Jingxin Zhang.

Dr. Ricardo Brau

Dr. Ke Liu

Dr. Nripen Singh

Questions and Discussion

Speakers and Organizing Committees

美丽的秋日的午歇正是新老朋友在MIT的Kendal， Technology Square院子里享受阳光和午餐桌边的讨论极佳时间。 下午会议由Dr. Hans G. Klingemann, Vice President of Research & Development from NantKwest，分享开始。 Dr 。Hans讲述了公司NK细胞抗癌项目的喜人结果。NantKwest是一家免疫疗法公司主要用NK细胞来治疗癌症。报告中，Hans博士分享了基于NK细胞的平台的进展和前景，该平台已经过生物工程改造，可以融合嵌合抗原受体（CARs）和抗体受体，从而有可能进一步优化疾病治疗的靶向性和效力。接下来，Dr. Jeffrey Palmer, Senior Director of Pfizer 分享了目前基因疗法临床试验及FDA审批的形势。他具体讲了FDA通过快速审批项目支持基因疗法。他用公司的hemophilia B 和 Duchenne muscular dystrophy的例子讲解了基因疗法的临床试验和审批的过程。同时他也说明了基因疗法临床试验面临的一些挑战， 包括1）样本量小； 2）临床试验暂停和回答问题的机会更少； 3）一些适应症没有确定的注册终点。 之后，Dr. Alasdair Milton, Vice President at Parthenon-EY讲解了公司怎样有效利用资源使基因疗法利益最大化。他生动形象地引用了Spark Therapeutics的例子，讲解了Spark如何提高生产效率，如何通过医疗专员来建立以患者为中心的药企-患者关系模型。 基因疗法临床试验面临的一个主要问题是如何 来准确地记录患者的治疗耐久性. 因为患者在接受基因治疗后症状往往得到很大改善，这样他们就不太会主动去跟进。 所以建立一个强大的药企-患者关系就尤为重要。

Drs. Qiying Hu, Hans G, Klinggemann and Jason Jingxin Zhang

Dr. Jerrery Palmer

Dr. Alasdair Milton

一杯咖啡和欢快的聊天之后，大家精神饱满地开始了会议的最后高潮部分-基因治疗在罕见病和癌症中的应用。来自SANOFI负责基因治疗，罕见病和神经疾病的科学主任Catherine O’Riordan博士首先讨论了AAV基因治疗在罕见遗传病领域的进展。从临床前研究，临床研究，FDA审批，以及生产各方面，AAV基因治疗都在走向成熟。许多新型的治疗方案都在使用AAV作为药物递送载体。紧接着，负责罕见病和代谢疾病的主任科学家Jingsong Cao博士代表Moderna跟大家分享了用mRNA治疗罕见代谢疾病的令人兴奋的结果。作为史上最大生物技术IPO公司，Moderna使用mRNA（被称为生命的软件）去刺激机体产生自己的药物蛋白，这就像在病人身体内建造了自己的药物工厂。Cao博士用有趣的临床前实验表明Moderna的mRNA技术可以在老鼠肝脏中产生葡萄糖6-磷酸酶，有效治疗糖原贮积病1a型。压轴的演讲嘉宾是哈佛医学院的Shields Warren Mallinckrodt 教授，RNA医学研究所主任Frank Slack博士。作为RNA研究领域的开创性科学家，Slack博士分享了用microRNA治疗癌症的基础研究和临床试验。从精准医学到免疫治疗，microRNA展现了成为新型癌症治疗方法的希望。

Dr. Catherine O’Riordan

Dr. Jingsong Cao

Prof. Frank J Slack

Dr Mangeng Cheng

前任美国药监局局长Scott Gottlieb和CBER总监Peter Marks于2019年1月15日共同发表的声明中强调：

“……我们预计，到2020年，我们将在FDA存档的800多种基于活性细胞或直接给药的基因治疗IND的基础上，每年接收200多个新的IND。到2025年，根据对当前产品线和这些产品的临床成功率的评估，我们预计FDA将每年批准10至20种细胞和基因疗法产品……。”

会议最后，由SAPA-NE新任主席Mengeng Cheng博士致辞。感谢组委会的不懈努力，志愿者和赞助商的大力支持。 SAPA-NE将继续我们的使命，以激发科学交流，促进药物研发和法规制定之间的合作和对话。Mengeng Cheng博士宣布第22届SAPA-NE年会的主题为"Developing and Delivering the Transformative Medicines for Unmet Medical Needs"。期待与您在2020年6月13日于波士顿万豪酒店（马萨诸塞州剑桥百老汇50号）举行的第22届SAPA-NE年会上再相见！

撰稿人：朱敏， 钱自清， 吕向民， 张开

审稿人：李惠娟

摄影师：杨栋