Overview

Our Mission




PhaseRx is dedicated to transforming families’ lives by creating better treatments for children with inherited diseases, actually correcting the problems at the source by replacing missing or damaged enzymes to allow the body’s natural processes to work.

We are developing a portfolio of mRNA products for inherited liver diseases, and in 2018 we expect to achieve clinical proof of concept in the first set of therapies to treat children born with life-threatening inherited liver diseases.

PhaseRx’s technology replaces missing or defective enzymes inside the liver cells, correcting the underlying cause of inherited liver diseases. This is achieved by intracellular enzyme replacement therapy (i-ERT) which targets synthesis of delivered mRNA specifically to liver cells.

Our current product portfolio focuses on treating urea cycle disorders (UCDs), which can result in cumulative and irreversible brain damage due to the liver’s inability to process ammonia from the blood. We believe our i-ERT technology can be applied to a significant number of other inherited liver diseases.

Market Opportunity

We are dedicated to transforming patients’ and families’ lives. We believe the intracellular enzyme replacement therapy (i-ERT) market opportunity is completely untapped and validated by the current $4 billion worldwide conventional enzyme replacement therapy (ERT) market. By replacing defective enzymes operating within cells, i-ERT is expected to enable the treatment of diseases which cannot be treated with conventional ERT, such as urea cycle disorders. In addition to urea cycle disorders, we expect our i-ERT therapeutic platform to be applicable to a significant number of other inherited liver diseases that cannot be treated with conventional ERT.

The FDA Orphan Drug Program provides economic incentives to encourage companies to develop treatments for rare diseases. This program has substantially increased industry research for orphan diseases since inception, and we expect to benefit from economic incentives available from this program.

Our technical advantages combined with the FDA incentives create an opportunity for positive social impact as well as commercial success.

Health Impact

Urea cycle disorders are typically diagnosed between birth and the age of twelve, and can lead to devastating consequences, including cumulative and irreversible brain damage, coma and death.

  • UCD patients live with a constant risk of becoming very sick due to increased levels of ammonia in the blood which cause brain damage and potentially fatal ammonia toxicity.
  • The only cure for UCDs is a liver transplant. Currently available drug treatments do not correct the disease, and do not eliminate the risk of life-threatening crises.

Without correction, even on the best available treatment (a strict diet, dietary supplements and ammonia scavengers) patients continue to be at risk for life-threatening crises caused by high blood ammonia.
Our i-ERT approach is designed to replace the missing urea cycle enzyme, return function to the urea cycle, and correct the damaging and potentially fatal build-up of ammonia in the blood in UCD patients.
Ultimately, we believe our therapies have the potential to eliminate the need for liver transplants in the most severely affected OTCD patients.

Innovative Delivery

A key challenge with mRNA therapeutics is effective delivery. Our Hybrid mRNA TechnologyTM platform is specifically designed to overcome barriers to administration of mRNA, and represents a sophisticated solution for delivering mRNA therapeutics.

  • Our technology platform combines a lipid nanoparticle with a proprietary polymer technology
    The lipid nanoparticlethat encapsulates and protects the fragile mRNA in the blood and delivers it to liver cells.
  • The polymer facilitates delivery of mRNAs into cells’ cytoplasm (intracellular delivery).
    Preclinical data suggest that our Hybrid mRNA TechnologyTM enables high levels of synthesis of the desired protein with good tolerability and without loss of effectiveness with repeat dosing.

Progress

Led by a team with extensive expertise in nucleic acid delivery technology, we have already generated positive preclinical data for two pipeline compounds and are progressing rapidly toward clinical trials.

  • Treatment with our lead product, PRX-OTC, has shown normalization of blood ammonia levels and100 percent survival in OTC-deficient hyperammonemic mice (the standard model for this disease), as well as a promising safety profile.
  • Similarly, PRX-ASL therapy showed statistically significant reduction in ammonia levels following two weeks of mRNA treatment in mice deficient in the enzyme argininosuccinate lyase (ASL).
    Based on our preclinical data, the company expects to achieve lowering of blood ammonia in our Phase 2a and 2b clinical proof-of-concept studies for PRX-OTC in 2018.
  • Lowering of blood ammonia is believed to be an approvable endpoint for the UCDs, since it was the basis for the FDA’s approval of current treatments to treat the UCDs in 2013.

Intellectual Property

We have a strong intellectual property portfolio covering the world’s major pharmaceutical markets, with over 30 patents issued and many patent applications pending which are either exclusively licensed from the University of Washington or invented by our own scientists. This patent portfolio covers: the polymer technology, Hybrid mRNA TechnologyTM, and structures of mRNA.