Cambridge Healthtech Institute’s Inaugural

Drug Discovery for Rare Diseases

Focus on Genomic and Proteomic Targets and Drug Modalities

March 28, 2018 | Boston Marriott Cambridge | Cambridge, MA

Rare diseases, or diseases that affect only a small percentage of the population, have been growing in significance and prominence in recent years. According to the National Institutes of Health, there are nearly 7,000 rare diseases and more than 25 million Americans who are affected. Approximately 80% of these rare diseases are genetic in origin. Cambridge Healthtech Institute’s symposium on Drug Discovery for Rare Diseases will bring together leading scientists, clinicians, executives and experts who are deeply involved in bringing to market the treatments for such rare disorders. This symposium will bring to light some of the new drug targets, and peptide and oligonucleotide-based drug modalities that are being pursued. This unique one-day event will bring together people from diverse backgrounds to tackle translational challenges and to discuss potential opportunities in this field. The goal is to help attendees and sponsors meet scientific and technical experts who are involved in rare disease research to exchange ideas and set up collaborations.

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. KmiecEric 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 MarshallWilliam 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) ManoharanMuthiah (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. GivenBruce 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.


Torsten Hoffmann, PhD, COO, Silence Therapeutics

Robert N. McBurney, PhD, CEO, Accelerated Cure Project for MS 

Heather Siefers, MS, Senior Manager, Clinical Biorepository Operations, Aeras and Chair, iConquerMS™ PPRN Governing Board


11:55 Enjoy Lunch on Your Own

12:25 pm Session Break

Exploring Innovative Strategies

1:15 Chairperson’s Remarks

James J. HickmanJames 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

Paglo_SardiS. Pablo Sardi, PharmD, PhD, R&D Director, Neuroscience, Sanofi 

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 FeinsteinElena 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 CoxGerry 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. KmiecEric. 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 Human-on-a-Chip Systems Applied to Rare Disease Investigations for Efficacy and Toxicity

James J. HickmanJames 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.

4:35 Case Study: Identification and Development of SLN124, a Conjugated GalNAc-siRNA Therapeutic for the Treatment of Iron Overload Disorders 

Torsten Hoffmann

Torsten Hoffmann, PhD, COO, Silence Therapeutics

Conjugation of the N-acetylgalactosamine (GalNAc) moieties to siRNAs allows precise and highly effective knockdown of various genes in the liver, specifically in hepatocytes, of the vertebrate organisms. We will describe how Silence Therapeutics develops novel therapeutic programs addressing hepatocyte-associated diseases using its proprietary GalNAc-siRNA technology. In this case study, the discovery of SLN124 will be described in greater detail.


 5:05 Close of Symposium

Present a Poster

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