Awarded Grants

Emily’s Entourage grants are aimed at top research talent pursuing high risk, high reward projects that have the potential to deliver breakthroughs to patients expeditiously. To date, Emily’s Entourage has awarded over $2.3 million to multi-disciplinary teams around the world.


Catalyst for a Cure Grants

The Catalyst for the Cure Campaign is a groundbreaking initiative to raise $3 million in three years to fund four key research areas targeting Cystic Fibrosis-related nonsense mutations. These strategic areas were identified by the Emily’s Entourage Scientific Advisory Board because they offer the greatest potential to accelerate development of cutting-edge treatments that can reach patients with nonsense mutations of CF within 5 years.

2017

Novel approaches to improve W1282X-CFTR functional expression in airway epithelia

Gergely L. Lukacs, MD, PhD                               McGill University                                                   Award Year: 2017

Using innovative biochemical techniques, the major aim of this project is to identify new targets to improve trafficking of CFTR1281, the truncated protein product that results from the W1282X mutation.

Catalyst for the Cure Strategy: Building a Toolbox: Understanding the Biology and Developing Models of Nonsense Mutations

Creating the W1282X-CFTR airway epithelial cell toolbox

Scott H. Randell, PhD                                               Finn Hawkins, MBBCh                                                 University of North Carolina at Chapel Hill                 Boston University                                                       Award Year: 2017

The absence of validated cell models has been a major barrier to the development of therapies for CFTR nonsense mutations. Scott H Randell, PhD, in collaboration with Finn Hawkins, MBBCh (Boston University) will develop W1282X homozygous airway epithelial cell models that should expedite therapeutic developments.

Catalyst for the Cure Strategy: Building a Toolbox: Understanding the Biology and Developing Models of Nonsense Mutations

Advancing small molecules to restore W1282X-CFTR function

 Alan S. Verkman, MD, PhD                        University of California, San Francisco                Award year: 2017

This project employs pioneering high throughput screening approaches to identify drug-like molecules that target W1282X-CFTR, and other rare CF mutations. In studies previously funded by Emily’s Entourage, Dr. Verkman established the concept that combined “correctors” and “potentiators” –  as used to treat the most common CF mutation, F508del– could also be used to treat the W1282X mutation. These new studies aim to progress this area.

Catalyst for the Cure Strategy: Browsing the Library: Identifying and Repurposing Therapeutic Molecules 

Using SPX1010 to normalize airway hydration in W1282X-CFTR epithelia

Robert Tarran, PhD                                       University of North Carolina at Chapel Hill             Award Year: 2017

A key characteristic of CF is thick, dehydrated mucus that accumulates in the lungs causing chronic bacterial infections. In patients with CF, an overactive protein called ENaC contributes to airway surface dehydration to drive this process. This project will investigate a novel therapeutic approach to rehydrate the airways using a preclinical candidate that inhibits ENaC.

Catalyst for the Cure Strategy: Creative Workarounds: Working with Alternative Pathways

Therapeutic repair of CFTR nonsense mutations

Christopher Ahern, PhD                             University of Iowa                                                         Award Year: 2017

This project uses an innovative genetic approach to correct the W1282X-CFTR mutation. Engineered transfer-RNA molecules will be used to direct delivery of an appropriate tryptophan (W) to the W1282X mutation during protein synthesis to promotes production of the full length CFTR protein.

Catalyst for the Cure Strategy: Spell Check: Fixing Mutations Through RNA Testing


2018

Efficacy of CFTR modulators on W1282X-CFTR mutation in intestinal organoids

 Jeffrey Beekman, PhD                                  University Medical Center Utrecht, Netherlands    Award Year: 2018 

The goal of this project is to investigate if current or investigational CFTR modulators are effective in organoids derived from CF subjects with the W1282X mutation. 

 Catalyst for the Cure Strategy: Browsing the Library: Identifying and Repurposing Therapeutic Molecules 

Novel therapeutic approaches for treatment of CF patients with the W1282X premature termination codon mutation

Venkateshwar Mutyam, PhD                         Steven M Rowe, MD, MSPH                                      University of Alabama at Birmingham                 Award Year: 2018 

Prior studies supported by Emily’s Entourage revealed that KALYDECO provides therapeutic benefit in some CF subjects with the W1282X mutation. These provocative studies will be extended in further n-of-1 clinical trials to assess whether clinical benefits can be further enhanced by an approved corrector-potentiator therapy.

Catalyst for the Cure Strategy: Browsing the Library: Identifying and Repurposing Therapeutic Molecules 

Improving W1282X CFTR airway epithelial cell function with small molecules

Theo Moraes, MD, PhD

Tanja Gonska, MD

Christine Bear, PhD

Felix Ratjen, MD, PhD, FRCPC

The Hospital for Sick Kids, Toronto Canada       Award Year: 2018

Combining expertise in cell culture, CFTR functional assessment, therapeutic development, and clinical practice, this project will assess whether available therapeutic approaches modulate key properties, including ion transport and mucociliary clearance, in airway epithelial cells derived from CF subjects with the W1282X mutation.

 

Catalyst for the Cure Strategy: Browsing the Library: Identifying and Repurposing Therapeutic Molecules 

A Molecular Prosthesis for CFTR-Independent treatment of CF caused by nonsense mutations

Martin D. Burke, MD, PhD                                   Michael J. Welsh, MD                                             University of Illinois at Urbana-Champaign University of Iowa                                                     Award Year: 2018 

CF is caused by loss of function of the CFTR ion channel. Development of alternative ways to restore missing channel function independently of CFTR is an urgent unmet medical need. Based on compelling studies in cell culture models and in CF animal models, this project will test a novel therapeutic strategy to directly address this need. This approach uses a drug approved for an alternative indication and could eventually lead to development of a novel therapeutic approach for CF.

 Catalyst for the Cure Strategy: Creative Workarounds: Working with Alternative Pathways 


Strategic Investments

Talee Bio

University of Iowa and Militia Hill Ventures       Beverly L. Davidson PhD                                           John F. Engelhardt, PhD                                           Paul B. McCray, Jr, MD                                         Michael Welsh, MD                                                   Joseph Zabner, MD                                                   Jane H. Hollingsworth                                                 Joan Lau, PhD, MBA                                                     Eric Yuen, MD                                                           Award Year: 2017 

Through a unique partnership with the University of Iowa and Militia Hill Ventures, Emily’s Entourage provided seed funding to launch Talee Bio, a biotech company focused exclusively on gene therapy to cure all mutations of CF. In a race against the clock, this venture philanthropy model can expedite advances by harnessing the power of venture capital.


Pilot Grants

This program is administered through and matched by the Penn Medicine Orphan Disease Center’s Million Dollar Bike Ride Pilot Grant Program. 

Rational design of effective therapeutics for treatment of the 1282X CFTR disorder

Barry Cooperman, PhD                                             University of Pennsylvania                                       Award Year: 2016 

Using synthetic chemistry in conjunction with biochemical approaches, the aim of this project is to identify the site of action of Ataluren, a drug that promotes premature stop codon readthrough, and to develop improved chemical analogs of this drug candidate.

Novel assay platforms and therapies for W1282X-CFTR

Christine Bear, PhD                                                        The Hospital for Sick Kids, Toronto, CA                Award Year: 2015 

This project considered two distinct areas to advance W1282X-CFTR targeted therapeutic development. The first objective was to develop assays of CFTR function in patient-derived cell samples to test efficacy of existing and new CF therapies. The second considered a novel genetic approach to overcome the W1282X mutation.

N-of-1 trials to validate therapies for W1282X-CFTR

Steven M. Rowe, MD, MSPH                                     University of Alabama                                           Award Year: 2015

The objective of this project was to assess current therapeutic options for the W1282X-CFTR mutation in a patient-specific manner. The major outcome of this study, reported in the Journal of Cystic Fibrosis, indicated that the potentiator Ivacaftor elicited CFTR-dependent current in a W1282X-CFTR subject.


Independent Grants

Small molecules to rescue the W1282X mutation in CFTR

 Alan S. Verkman, MD, PhD                       University of California, San Francisco                Gergley L. Lukacs, PhD                                                 McGill University                                                              Award Year: 2015 

This project aimed to establish a novel paradigm for therapy for the W1228X-CFTR mutation. Studies developed initial small molecule discovery platforms and provided the first evidence that a combined “correctors” and “potentiators” — as used to treat the most common CF mutation, F508del — could also be used to treat the W1282X mutation.

 

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