ARPA-H awards up to $160 million to advance personalized curative medicines for rare genetic diseases 

Program performer teams will build toward the department's goal of accelerating the development and approval of rare disease therapies 

The Advanced Research Projects Agency for Health (ARPA-H), an agency within the U.S. Department of Health and Human Services, today announced the teams for the Treating Hereditary Rare Diseases with In Vivo Precision Genetic Medicines (THRIVE) program — a critical investment toward bringing new treatments to patients faster and cure rare genetic pediatric diseases. THRIVE will accelerate solutions across multiple technological approaches, clinical trial designs, and deployment models for a diverse set of rare genetic diseases, all of which are devastating and life-threatening. 

“By transforming precision genetic medicines through platforms that can test multiple treatments for multiple diseases in a single clinical trial, THRIVE reflects the kind of groundbreaking health innovation needed to help children and families facing life-threatening genetic diseases,” said Alicia Jackson, Ph.D., ARPA-H Director. “This ARPA-H program takes on one of the toughest challenges in medicine — and could change the trajectory of genetic disease, expand access to advanced treatments, and reinforce U.S. leadership in the future of medicine.” 

Life-threatening rare genetic diseases affect millions of Americans, many of them newborns, infants, and children, with no treatments for the root cause. Despite their critical unmet treatment needs, about 95% of rare diseases have no approved medicines and the traditional model of one disease, one treatment, one trial adds cost and time to a research process where every dollar and everyday count. 

“Our current system is built to develop one drug for one disease tested in clinical trials designed specifically for that drug and that disease. Patients with rare genetic diseases, especially children, cannot wait for this legacy approach, it’s too slow and unsustainable. THRIVE will blaze a new trail and change that — using a modular building-block approach that swaps one key piece instead of rebuilding the whole set for every disease,” said THRIVE Program Manager Daria Fedyukina, Ph.D. “This innovative umbrella clinical trial model will engage patients and their families to help shape clinical trials and make sure these treatments can rapidly and affordably reach the people who need them.” 

The core goal for THRIVE teams will be to develop pioneering integrated platform technologies to accelerate personalized genetic medicines to cure rare pediatric diseases at the root cause. In the first year, teams must demonstrate gene editing platforms capable of generating multiple drug products with common biodistribution and toxicology profiles. By year three, teams will have begun first-in-human trials where one trial will, for the first time, accommodate several different products and several disease phenotypes. At year five, teams must demonstrate successful expansion of umbrella investigational new drug application (IND) and clinical trials with additional drug products and diseases and validate novel deployment models. Across the program, through frequent publications and demonstrations, the teams will teach their rare disease colleagues across the country how to replicate this path.

ARPA-H’s commitment is up to $160 million over five years. Performer awards vary in funding amount per awardee and are contingent upon each team meeting aggressive and accelerated milestones. Clinical and regulatory innovations are mandatory in the program.   

Performer teams are led by: 

The Children’s Hospital of Philadelphia: The team will build upon teams’ success in developing kayjayguran abengcemeran, which was made for an infant with a severe UCD (neonatal-onset CPS1 deficiency). They will expand the platform approach to treat at scale many rare metabolic and hematological diseases caused by pathogenic mutations. 

University of California, Berkeley, Innovative Genomics Institute 
The team will develop in vivo gene editing platforms to address life-threatening inborn errors of immunity. The team will integrate a novel rapid non-invasive patient identification method to support clinical development and ultimate real-world deployment. 

St. Jude Children’s Research Hospital Inc.: The team will be developing genetic medicines for bone marrow failure disorders under one umbrella clinical trial, supported by the most sensitive and accurate off-target detection methods. 

The Broad Institute Inc.: The team in partnership with multiple suborganizations will pursue cures for pediatric epilepsies caused by genetic mutations. The team also pioneers a novel deployment model for genetic therapies to improve sustainable deployment of these and future treatments. 

GEMMABio: This team, supported by Profluent Bio, will be developing an AI/ML-based platform for highly modular gene editors. Such gene editors promise ultimate scalability as opposed to current bespoke and artisanal editors. The team will be developing curative approaches for genetic diseases, including those that lead to extreme cholesterol levels due to inheritance. 

Massachusetts General Hospital: The team aims to develop treatments for rare genetic diseases of blood vessels. In addition to advancing non-viral delivery of gene editors to vasculature, they will also advance in vitro 3D models of human blood vessels for rapid testing, thereby eliminating slow animal studies. 

Stanford University: The team aims to target a group of rare genetic skin diseases called Epidermolysis Bullosa (EB) with a topical gene editing approach. Patients with EB have fragile skin that easily blisters and develops non-healing painful wounds leading to increased mortality.  

For more on THRIVE, visit the program page.