Cambridge Healthtech Institute第一届

Drug Discovery for Rare Diseases

( 罕见疾病疗法的开发 )

聚焦于基因体标的、蛋白质体标的、药物形式的论坛

2018年3月28日 | Boston Marriott Cambridge | 马萨诸塞州剑桥

罕见疾病是影响非常少数人的疾病,近年来其重要度及关注程度逐渐提升。美国国家卫生研究院指出,现在世界上有将近7,000种罕见疾病的存在,超过2,500万美国人罹患这些疾病,而约有80%的罕见疾病被认为与基因有关。本论坛以罕见疾病疗法的开发为主题,开发各种罕见疾病疗法的主要研究人员、临床医师、企业干部、专家将聚集于此,针对新创药标的、正在研究的胜肽与低聚核苷酸药物形式等主题进行议论。本论坛为时一天,各种专业领域的人齐聚一堂,探讨转译研究的课题,针对本领域潜在商业机会交换意见,不但是独一无二的活动,协助研究罕见疾病的研究人员与专业技术人员,和赞助商企业干部交换意见、建立合作关系也是重要的目的之一。


Final Agenda

Wednesday, March 28

7:30 am Registration and Morning Coffee

Exploiting Diverse Drug Modalities & Targets

8:15 Welcome Remarks from Conference Director

Tanuja Koppal, PhD, Conference Director, Cambridge Healthtech Institute

8:25 Chairperson's Opening Remarks

Eric B. Kmiec, PhD, Director, Gene Editing Institute; Senior Research Scientist, Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System

8:30 Targeting microRNA-155 as a Therapeutic Strategy for Rare Hematological Malignancies

William Marshall, PhD, President and CEO, miRagen Therapeutics

microRNA-155 is an important control point for regulation of pathways implicated in oncology and inflammatory disease. Its overexpression has been shown to be an indicator of poor prognosis in a variety of rare hematological malignancies. MRG-106, an inhibitor of miR-155, is currently being evaluated in Phase I in patients with Cutaneous T-cell Lymphoma (CTCL). An overview of our latest clinical observations will be presented.

9:00 Chemistry and Biology of Rare Diseases Treatable with Hepatocyte Targeted RNAi Therapeutics

Muthiah (Mano) Manoharan, PhD, Senior Vice President, Drug Discovery, Alnylam Pharmaceuticals

9:30 The Natural History of Alpha-1 Antitrypsin Storage Disease and RNAi Intervention in PiZ Transgenic Mice and Implications for Treatment in Humans

Bruce D. Given, MD, COO, Arrowhead Pharmaceuticals

A large majority of patients with alpha-1 antitrypsin deficiency produce a mutant protein that mis-folds in the hepatocyte leading to deficiency in the plasma, but a storage disease in the liver. The PiZ transgenic mouse expresses the human mutant Z protein and recapitulates most of the human natural history in the liver. We have intervened throughout this natural history with RNAi trigger compounds and showing beneficial effects and are now entering the clinic with a second-generation RNAi compound.

10:00 Networking Coffee Break

10:30 Targeting the Pulmonary Vasculature with Oligonucleotide Therapy: Fact or Fiction?

Hyung Chun, MD, FAHA, Associate Professor of Medicine, Section of Cardiovascular Medicine, Yale School of Medicine

Pulmonary arterial hypertension is a rare disease that leads to right heart failure and ultimately death. While many studies have implicated the potential therapeutic role of oligonucleotides (including microRNAs, microRNA inhibitors, and short interfering RNAs), challenges have surrounded the efficient delivery of such oligonucleotides to the pulmonary vasculature. Current state of technology and future directions will be discussed.

11:00 PANEL DISCUSSION: Tackling Rare Diseases: From Conviction to Cure

Moderator: Michael Liebman, PhD, Managing Director, Strategic Medicine, Inc.

Panelists:

Torsten Hoffmann, PhD, COO, Silence Therapeutics

Nicholas Sarlis, MD, PhD, CMO and Senior Vice President, Sellas Life Science Group Ltd.

11:30 Sponsored Presentation (Opportunity Available)

11:45 Session Break

11:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:25 pm Session Break

Exploring Innovative Strategies

1:15 Chairperson's Remarks

James J. Hickman, PhD, Founding Director, NanoScience Technology Center; Professor, Nanoscience Technology, Chemistry, Biomolecular Science, Material Science and Electrical Engineering, University of Central Florida

1:20 From Rare to Common: Targeting Gaucher Defects for the Treatment of Parkinson's Disease

S. Pablo Sardi, PharmD, PhD, R&D Director, Sanofi Genzyme

Clinical, genetic and experimental evidence underlies the relevance of lysosomal dysfunction in Parkinson's disease. Stimulation of the lysosomal GBA pathway in the CNS can improve the pathological and behavioral abnormalities in animal models of disease. Modulation of this lysosomal pathway may represent a new disease-modifying treatment for GBA-related Parkinson's disease. This research underscores the study of rare diseases as a new paradigm for drug discovery.

1:50 Orphan Indications as a Step to Developing Therapeutics for Major Unmet Medical Needs

Elena Feinstein, MD, PhD, CSO, Quark Pharmaceuticals

This talk will present Quark's strategy of drug development from proof-of-concept in orphan indications to major ones with similar underlying pathogenesis. A case study of development of QPI-1002, an siRNA targeting p53, from an orphan indication such as delayed graft function following kidney transplantation towards acute kidney injury following cardiac surgery will be discussed.

2:20 Preclinical Development of a CRISPR Medicine for the Treatment of Leber Congenital Amaurosis Type 10

Gerry Cox, MD, CMO, Editas Medicine

A common mutation in intron 26 of the CEP290 gene, c.2991+1655A>G, leads to retinal degeneration and infantile-onset blindness known as Leber congenital amaurosis type 10 (LCA10). A therapeutic approach involving subretinal delivery of AAV5 encoding CRISPR components is being developed to remove the mutation and potentially restore vision. Opportunities and preclinical challenges of developing human genome-based medicines for LCA10 will be discussed.

2:50 Efficient Delivery and Nuclear Uptake for Gene Editing in CD34+ Cells Directed by a CRISPR/Cas9 Ribonucleoprotein Complex

Eric. B. Kmiec, PhD, Director, Gene Editing Institute; Senior Research Scientist, Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System

Successful editing of the beta globin gene in CD34+ cells is a milestone for ex vivo cell therapy. While dramatic advances have been reported in the literature, by and large, the experimental protocols and conditions have been less than robust. We began a systematic evaluation of the relationship among cellular delivery, nuclear uptake and gene editing activity and defined the critical parameters for CRISPR/Cas9 RNP and ssODNs delivery into CD34+ cells.

3:20 Networking Refreshment Break

3:35 Developing a First-in-Class Drug for Familial Amyloid Polyneuropathy: A Case Study

Christine Bulawa, PhD, Senior Director, Rare Disease Research Unit, Pfizer

This talk will present a case study of drug development for familial amyloid polyneuropathy (FAP), a disease caused by mutations in the circulating protein transthyretin. Insights gleaned from biophysical studies of transthyretin and clinical observations of FAP patients led to the therapeutic strategy of native state stabilization and ultimately to development of tafamidis, the first disease modifying therapy for an amyloid disease.

4:05 Application of Genome Editing to Develop HTS Assays for Rare and Neglected Disease Drug Discovery

James Inglese, PhD, Head, Assay Development & Screening Technologies, National Center for Advancing Translational Sciences, NIH

Genome editing was used in combination with reporter gene technology to modify the genetic loci of neurologic target genes to create HTS assays for compound library interrogation. Assay design explored cases of gene duplication, haploinsufficiency, or genes with implied protective properties, associated with Charcot-Marie-Tooth type 1A, Dravat syndrome, or Parkinson's disease, respectively. Our goal was to identify transcriptionally active pharmacological agents acting by a variety of mechanisms, including through chromatin coregulators accessible by our assay design.

4:35 Human-on-a-Chip Systems Applied to Rare Disease Investigations for Efficacy and Toxicity

James J. Hickman, PhD, Founding Director, NanoScience Technology Center; Professor, Nanoscience Technology, Chemistry, Biomolecular Science, Material Science and Electrical Engineering, University of Central Florida

Our focus is on establishing functional in vitro systems where we seek to create organs and subsystems to model motor control, muscle function, myelination and cognitive function, as well as cardiac and hepatocyte subsystems for neurodegenerative diseases such as ALS as well as other rare diseases. Functional 2 and 4-organ systems where multi-organ toxicity as well as efficacy are evaluated will be discussed.

5:05 Close of Symposium

* 活动内容有可能不事先告知作更动及调整。