2017 Archived Content

Tackling Rare Diseases

Rare diseases, or diseases that affect only a small percentage of the population, are growing in significance and prominence in recent years. According to the National Institutes of Health, there are more than 25 million Americans suffering from one of nearly 7000 rare diseases identified, yet there are only about 250 specific or appropriate treatments available. Approximately 80% of these rare diseases are genetic in origin. Cambridge Healthtech Institute’s symposium on Tackling Rare Diseases will bring together leading scientists, clinicians, executives and experts who are deeply involved in developing treatments for rare disorders and bringing them to market. This symposium will highlight the development of new therapeutic modalities and the use of innovative technologies and approaches to overcome translational challenges, and will bring together people from diverse backgrounds to discuss potential opportunities in this field. This unique one-day event will help attendees meet experts from around the world to exchange ideas and set up collaborations.

Final Agenda


• September 25 Symposium: Constrained Peptides and Macrocyclics

• September 26-27 Conference: CRISPR for Disease Modeling and Target Discovery

• September 27-28 Conference: Emerging Oligonucleotide Therapeutics

• September 28-29 Symposium: Tackling Rare Diseases

Thursday, September 28

4:00 pm Registration

Regulatory Perspectives & Innovative Strategies

5:25 Welcome Remarks

Tanuja Koppal, Ph.D., Conference Director, Cambridge Healthtech Institute

5:30 Chairperson’s Remarks

Adam Hutchings, Director, Dolon Ltd.

5:40 FEATURED PRESENTATION: Rare Disease Landscape: Fact Sheets in Research and Service Delivery

Ségolène_AyméSégolène Aymé, Emeritus Director of Research, French Institute of Health and Medical Research (INSERM); Expert in Residence for Rare Diseases, Brain and Spine Institute, Paris; and Editor-in-Chief, Orphanet Journal of Rare Diseases

The importance of rare diseases, as a driver for innovation in science and in healthcare organization, is now established and many indicators demonstrate that incentives have been instrumental in shaping the current situation. However, clouds are accumulating as many stakeholders question the affordability of the new diagnostic and therapeutic options. Joined efforts of the various stakeholders are necessary to keep this sector alive.

6:10 Overview of Key Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL)

Adam Hutchings, Director, Dolon Ltd.

To help improve the speed and consistency of patient access to orphan medicines, a European multi-stakeholder group of rare disease experts, ORPH-VAL, has proposed a set of common principles to improve the consistency of decision making for orphan drugs and balance the needs of innovators and payers. Policymakers and rare disease stakeholders should engage with these recommendations, explore areas where local P&R systems diverge from the principles, and identify and enact potential reforms, all with the goal of improving overall access to medicines for patients with rare diseases.

6:40 Close of Day

Friday, September 29

8:00 am Registration and Morning Coffee

Exploring Phenotypic Screening, Stem Cell Models and More

8:30 Chairperson’s Remarks

Ronald Alfa, M.D., Ph.D., Vice President, Discovery & Product, Recursion Pharmaceuticals

8:40 Development of Multi-Modal Small Molecule Therapeutics for the Neuronal Ceroid Lipofuscinoses

Paul Trippier, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center

The neuronal ceroid lipofuscinoses (NCLs), although rare, are the most common neurodegenerative disorders of childhood. We have developed a patient-specific induced pluripotent stem cell (iPSC) model of CLN3 disease (Batten disease) in which we have screened a library of proprietary small molecules. This phenotypic screen has identified neuroprotective small molecules with translational activity in patient specific cells. Our mechanism of action studies reveal a novel multi-modal mechanism of action suitable for treating other neurodegenerative disorders.

9:10 Disease Modeling: Even Rare Diseases Are Complex

Michael Liebman, Ph.D., Managing Director, IPQ Analytics, LLC; Adjunct Professor of Pharmacology and Physiology, Drexel College of Medicine

Pediatric ARDS, a rare disease, presents challenges in diagnosis and treatment because it is a syndrome and exhibits significant heterogeneity in patients and their symptoms in spite of the specific diagnosis. The Nathaniel Adamczyk Foundation has been involved in developing a clinical research and decision support platform to catalyze the formation of a community that focuses on these challenges and enables hypothesis development and testing with unique analytic tools.

9:40 Massive Parallelization of Rare Disease Drug Discovery

Ron_AlfaRonald Alfa, M.D., Ph.D., Vice President, Discovery & Product, Recursion Pharmaceuticals

Recursion has developed a target agnostic discovery platform that combines artificial intelligence with automated biology for massive parallelization of high-throughput drug screening. In this session, I will describe our platform and provide a case study of drugs identified for a rare genetic disease.

10:10 Networking Coffee Break

New Therapeutic Modalities

10:40 A New Approach to Block ERAD and Reduce the Degradation of Partially Misfolded Mutant Proteins

Clifford LingwoodClifford Lingwood, Ph.D., Senior Scientist, Molecular Structure and Function, Hospital for Sick Children

Many genetic diseases result from the ER associated degradation (ERAD) of the partiallly misfolded mutant protein. Several bacterial/plant subunit toxins (e.g. cholera, Shiga toxin) hijack this pathway to achieve A subunit cytosolic access by using the same ER translocon. By A subunit mutagenesis we generate a benign toxoid which remains an ER translocon substrate, and as such is a temporary, competitive inhibitor of the ER translocon which partially rescues the deficiency disease phenotype in cell culture (e.g. F508delta CFTR of CF, N370S GCC of Gaucher’s).

11:10 The Potential of RNAi in Orphan Diseases – The Alpha 1 Anti-Trypsin Liver Disease Example

Dawn Christianson, Ph.D., Senior Program Manager, Arrowhead Research Corporation

Alpha 1 anti-trypsin deficiency is named a deficiency state because it is usually caused by a gene mutation which prevents the synthesized protein from exiting the liver, resulting in emphysema. However, in the liver it is a storage disease and with better pulmonary care and survival, patients are dying from liver disease or requiring transplant. RNAi is an apt approach to treating the liver disease, as evidenced by studies in animals and humans.

11:40 Sponsored Presentation (Opportunity Available)

12:10 pm Enjoy Lunch on Your Own


1:45 Chairperson’s Remarks

Ryan Hartmaier, Ph.D., Senior Scientist, Cancer Genomics, Foundation Medicine, Inc.

1:50 Engineering Tissue-Specific Delivery of Enzymes for Treatment of Lysosomal Diseases

Katherine Cygnar, Ph.D., Staff Scientist, Genome Engineering Tech, Regeneron Pharmaceuticals


2:20 Gene Discovery Efforts in Pediatric Patients with Undiagnosed Conditions

Pankaj_AgrawalPankaj B. Agrawal, M.D., MMSC, Geneticist and Medical Director, Gene Discovery Core, Manton Center for Orphan Disease Research, Boston Children’s Hospital; Assistant Professor, Pediatrics, Harvard Medical School    

Gene discovery core of the Manton Center at Boston Children’s Hospital is focused on identifying genes for rare disease patients with unexplained conditions. We have identified several novel genes using latest sequencing technologies and confirmed pathogenicity using cellular and animal models thereby advancing science and helping those families. This needs collaboration between clinicians, genetic counselors, bioinformaticians and basic scientists, long-term goals being to find appropriate therapies.

2:50 Leveraging Cancer Genomics to Identify Targetable Mutations in Rare Cancer Types

Ryan_HartmaierRyan Hartmaier, Ph.D., Senior Scientist, Cancer Genomics, Foundation Medicine, Inc.

The scarcity of genomic data in rare cancer types is a challenge for identifying and developing effective therapeutics. Here we explore the genomics of rare cancer types for novel, potentially druggable genomic alterations. Further, we surveyed the spectrum of known clinically relevant genomic changes to identify potential opportunities for broader utility of approved targeted agents in novel cancer types.

3:20 Familial Amyloid Polyneuropathy: How a Genetic Disease Informs Drug Discovery

Christine Bulawa, Ph.D., 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 and only disease modifying therapy for an amyloid disease.

3:50 Close of Symposium