Investigational Therapy Designed to Engineer Patients’ Own Stem Cells to Produce Essential Protein

CAMBRIDGE, MA, USA I October 08, 2019 IAVROBIO, Inc. (NASDAQ: AVRO) (the “Company”) today announced that the first patient has been dosed in the Company’s AVR-RD-04 investigational gene therapy program for cystinosis, a devastating lysosomal storage disease, in an ongoing Phase 1/2 clinical trial sponsored by academic collaborators at the University of California San Diego. The gene therapy is derived from the patient’s own hematopoietic stem cells, which are genetically modified to produce functional cystinosin, a crucial protein that patients with cystinosis lack.

The trial will enroll up to six patients with cystinosis, a rare inherited disease caused by a defect in the gene that encodes for cystinosin. The cystinosin protein enables transport of the amino acid cystine out of lysosomes. When it is absent, cystine accumulates and crystalizes, causing progressive damage to the kidneys, liver, muscles, eyes and other organs and tissues. Cystinosis affects both children and adults; they face shortened life spans and often painful symptoms, including muscle wasting, difficulty breathing, blindness and kidney failure.

“Cystinosis is a debilitating and progressive disease, and new treatment options are sorely needed. The current standard of care does not avert deterioration; at best, it can attenuate symptoms. That’s why gene therapy is particularly exciting: It has the potential to change the course of disease — and the lives of patients — by addressing the underlying cause of cystinosis,” said Birgitte Volck, MD, PhD, President of Research and Development at AVROBIO. “We believe we can engineer patients’ own stem cells so they sustainably produce the functional protein that is needed to prevent a toxic buildup of cystine and halt progression of the disease. We are so pleased that this investigational gene therapy is now in the clinic in collaboration with Dr. Stephanie Cherqui at UC San Diego.”

The single-arm trial will enroll four adults and a potential follow-on cohort of two adults or adolescents at least 14 years of age who are currently being treated with cysteamine, the standard of care for cystinosis. If started at an early age and taken on a strict dosing schedule, cysteamine can delay kidney failure. However, the treatment regimen is highly burdensome, with side effects that can be severe and unpleasant, and many patients find it difficult to adhere to this treatment regimen. Even if compliance is high, cysteamine therapy cannot prevent kidney failure or avert other complications.

“For people with cystinosis, there are no healthy days. They must take dozens of pills a day, around the clock, just to stay alive. It is a relentless disease and we urgently need new treatments,” said Nancy J. Stack, President of the Cystinosis Research Foundation, which supported development of the gene therapy with more than $5.4 million in grants to Dr. Cherqui’s lab at UC San Diego. “We believe that we are now an important step closer to the potential cure that our community has been working toward for many years.”

The trial’s primary endpoints are safety and tolerability, assessed for up to two years after treatment, as well as efficacy, as assessed by cystine levels in white blood cells. Secondary endpoints to assess efficacy include changes in cystine levels in the blood, intestinal mucosa and skin and cystine crystal counts in the eye and skin. Efficacy will also be evaluated through clinical tests of kidney function, vision, muscle strength, pulmonary function and neurological and psychometric function, as well as through assessments of participants’ quality of life after treatment. The trial is funded by grants to UC San Diego from the California Institute for Regenerative Medicine (CIRM) as well as the Cystinosis Research Foundation.

“This investigational gene therapy starts with the patients’ own stem cells, which are genetically modified so that their daughter cells can produce and deliver functional cystinosin to cells throughout the body. With this approach we aim to prevent the abnormal accumulation of cystine that causes so many devastating complications,” said Stephanie Cherqui, PhD, an Associate Professor of Pediatrics at UC San Diego School of Medicine, and consultant to AVROBIO. “We have been working toward this trial for years and we are grateful for all the support that brought us to this moment.”

About AVR-RD-04

AVR-RD-04 is a lentiviral-based gene therapy designed to potentially halt the progression of cystinosis with a single dose of the patient’s own hematopoietic stem cells. The stem cells are genetically modified so they can produce functional cystinosin with the aim of substantially reducing levels of cystine in cells throughout the patient’s body. Before the infusion of the cells, patients undergo personalized conditioning with busulfan to enable the cells to permanently engraft. The Phase 1/2 clinical trial is being conducted under the name CTNS-RD-04 by AVROBIO’s academic collaborators at the University of California, San Diego.

About Cystinosis

Cystinosis is a rare, inherited lysosomal storage disorder characterized by the accumulation of cystine in all the cells of the body, resulting in serious and potentially fatal damage to multiple organs and tissues and the shortening of patients’ life spans. The kidneys and eyes are especially vulnerable; more than 90% of untreated patients require a kidney transplant before age 20. An estimated 1 in 170,000 people are diagnosed with cystinosis.

About AVROBIO, Inc.

AVROBIO, Inc. is a leading, Phase 2 gene therapy company focused on the development of its investigational gene therapy, AVR-RD-01, in Fabry disease, as well as additional gene therapy programs in other lysosomal storage disorders including Gaucher disease, cystinosis and Pompe disease. The Company’s plato™ platform includes a proprietary vector system, automated cell manufacturing solution and a personalized conditioning regimen deploying state-of-the-art precision dosing. AVROBIO is headquartered in Cambridge, MA and has offices in Toronto, ON. For additional information, visit