Cambridge Healthtech Institute 제1회

Drug Discovery for Rare Diseases

(희귀질환용 Drug Discovery)

게놈 표적, 프로테오믹스 표적, 의약품 모달리티에 초점을 맞춘 심포지엄

2018년 3월 28일 | Boston Marriott Cambridge | 매사추세츠주 케임브리지

희귀질환이란 극소수의 사람들에게 영향을 미치는 질환으로, 최근 중요도와 주목도가 높아지고 있습니다. 미국국립보건원에 따르면 현재 세계에는 약 7,000 종류의 희귀질환이 존재하며, 2,500만명 이상의 미국인이 희귀질환을 앓고 있다고 합니다. 또한 희귀질환의 약 80%는 유전자가 관련되어 있는 것으로 추산됩니다. 희귀질환용 Drug Discovery를 테마로 한 이 심포지엄에서는 각종 희귀질환용 치료법의 개발에 깊이 관련되어 있는 주요 연구자 및 임상의, 기업 임원, 전문가가 참가하여 새로운 의약품 표적, 현재 연구가 진행되고 있는 펩티드와 올리고뉴클레오티드를 기반으로 한 의약품 모달리티 등의 토픽에 대해 논의합니다. 종일 진행되는 이 심포지엄은 다양한 전문 분야의 인사가 모여 중개연구 문제에 주력하면서 이 분야의 유망 비지니스 기회에 대해 의견을 교환하는 유일한 이벤트로, 희귀질환 연구자 및 기술 전문가가 다른 참가자 및 스폰서 기업의 임원과 아이디어를 교환하거나 협력 관계를 구축하는 것을 지원합니다.


Final Agenda

3월 28일(수)

7:30 am Registration and Morning Coffee

각종 약제의 모달리티와 표적의 이용

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

혁신적인 전략의 이용

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

* 주최측 사정에 따라 사전 예고없이 프로그램이 변경될 수 있습니다.