FLT201 is a highly differentiated AAV gene therapy candidate that delivers a longer-acting engineered variant of GCase, the enzyme missing in people with Gaucher disease

Company expects to report initial clinical data for FLT201 in third quarter of 2023

Parkinson’s disease program leverages same longer-acting GCase enzyme as FLT201, with aim of developing a gene therapy for genetically defined patient subset with GBA1 mutations

LONDON, UK I June 26, 2023 IFreeline Therapeutics Holdings plc (Nasdaq: FRLN) today announced that the first patient has been dosed in the Phase 1/2 GALILEO-1 clinical trial evaluating FLT201, its adeno-associated virus (AAV) gene therapy candidate, in Gaucher disease type 1. Gaucher disease is a debilitating genetic disorder in which a deficiency of the GCase enzyme leads to a buildup of fatty substances in the organs, causing symptoms including enlarged spleen and liver, low blood counts, bone pain and reduced lung function.

“We believe that FLT201 has life-changing potential for people with the most common type of Gaucher disease,” said Pamela Foulds, M.D., Chief Medical Officer at Freeline. “Existing therapies do not sufficiently penetrate deeper tissues, and enzyme levels wane in between infusions, giving harmful substrates the opportunity to build back up in all disease-affected organs. FLT201 is a highly differentiated gene therapy candidate for Gaucher disease type 1 that delivers a longer-acting, rationally engineered enzyme. Preclinically, FLT201 has been shown to produce sustained levels of enzyme and penetrate deeper tissues, including bone and lung, giving us reason to believe it has the opportunity to stop disease progression and improve outcomes with a one-time treatment.”

“The dosing of the first patient in the GALILEO-1 trial of FLT201 marks an important step forward for the Gaucher community,” said Dr. Ozlem Goker-Alpan, founder and CEO of the Lysosomal and Rare Disorder Research and Treatment Center (LDRTC) and an investigator in GALILEO-1. “There is a clear need for better treatment options. Existing therapies come with a heavy lifelong treatment burden, and many patients continue to experience serious symptoms. FLT201 represents a promising approach for addressing the underlying cause of Gaucher disease with a one-time gene therapy, potentially providing a more effective and less burdensome option for patients. I look forward to further evaluating FLT201 in this clinical trial.”

GALILEO-1 is a first-in-human, international, multicenter Phase 1/2 dose-escalation study. The trial will assess safety, tolerability and efficacy of a single intravenous dose of FLT201 in up to four cohorts of escalating doses, with the aim of identifying a dose for further development in a Phase 3 clinical trial. Visit clinicaltrials.gov to learn more about GALILEO-1.

Freeline expects to report initial data, with a focus on safety and enzyme activity, from the first cohort of GALILEO-1 in the third quarter of this year.

Extending Innovation into GBA1-linked Parkinson’s Disease
Freeline unveiled its research program in GBA1-linked Parkinson’s disease. The program builds on its work with Gaucher disease, leveraging its rationally engineered longer-acting GCase variant to extend the impact of its innovation to develop a gene therapy candidate for a subset of Parkinson’s disease patients with mutations in the GBA1 gene, which encodes for GCase. As in Gaucher disease, the GBA1 mutations lead to a deficiency of GCase and the accumulation of pathological substrates. GBA1 mutations increase the risk of developing Parkinson’s disease by up to 30-fold and are associated with earlier onset of disease, more severe symptoms and increased likelihood of progression to dementia.

“Our GBA1-linked Parkinson’s disease program is a natural extension of our work in Gaucher disease and an opportunity to extend the therapeutic potential of our longer-acting GCase variant into a genetically defined patient population with a serious unmet need,” said Michael Parini, Chief Executive Officer at Freeline. “There are no approved disease modifying therapies for Parkinson’s disease, and symptomatic treatments become less effective as the disease progresses. Preclinically, our GCase variant has demonstrated at least 20-fold greater activity levels compared to wildtype enzyme in various cell lines, including brain epithelial and neuroblastoma cells, and our goal is to leverage our longer-acting GCase variant to create a life-changing gene therapy for this patient population.”
About Gaucher Disease
Gaucher disease is caused by a mutation in the GBA1 gene that results in abnormally low levels of glucocerebrosidase (GCase), an enzyme needed to metabolize a certain type of lipid. As a result, harmful substrates glucosylceramide (Gb-1) and glucosylsphingosine (lyso-Gb1) build up in cells that then accumulate in various organs, causing inflammation and dysfunction. Gaucher disease is hereditary and presents in various subtypes. Freeline is currently focused on Gaucher disease type 1, the most common form of the disease, which affects the health of the spleen, liver, bone and lungs. Despite treatment with existing therapies, many people with Gaucher disease continue to experience symptoms and disease progression. Gaucher disease affects approximately 18,000 people in the United States, United Kingdom, France, Germany, Spain, Italy and Israel.

About GBA1-linked Parkinson’s Disease
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that results in tremors, muscle rigidity, difficulty walking, anxiety, depression and cognitive impairments. Approximately 5-15% of PD patients have mutations in the GBA1 gene, which encodes for the glucocerebrosidase (GCase) enzyme. The most common genetic risk factor for PD, GBA1 mutations increase the risk of developing PD by 5- to 30-fold. GBA1 mutations are also associated with earlier onset and more severe disease. There are no approved disease-modifying therapies for PD, and current treatments, which focus on managing symptoms, become less effective over time. Freeline estimates GBA1-linked PD affects approximately 190,000 patients in the United States, United Kingdom, France, Germany, Spain and Italy.

About FLT201
FLT201 is an adeno-associated virus (AAV) gene therapy candidate that is currently being investigated in the GALILEO-1 Phase 1/2 clinical trial in adults with Gaucher disease type 1. FLT201 is designed to generate durable increases in glucocerebrosidase (GCase) and reduce the accumulation of harmful substrates, with the aim of providing a one-time treatment that can stop disease progression, improve outcomes and free people from lifelong treatment. FLT201 uses Freeline’s proprietary AAVS3 capsid to introduce a novel transgene into liver cells to produce a rationally engineered GCase variant. In preclinical studies, the GCase variant has demonstrated a 20-fold increase in half-life at lysosomal pH conditions compared to wildtype human GCase. Preclinically, FLT201 has shown robust GCase expression, as well as significant GCase uptake and substrate reduction in key tissues.

About Freeline Therapeutics
Freeline is a clinical-stage biotechnology company focused on developing transformative gene therapies for chronic debilitating diseases. Freeline uses its proprietary, rationally designed AAV vector and capsid (AAVS3), along with novel promoters and transgenes, to deliver a functional copy of a therapeutic gene into human liver cells, thereby expressing a persistent functional level of the missing or dysfunctional protein into a patient’s bloodstream. The company is currently advancing FLT201, a highly differentiated gene therapy candidate that delivers a novel transgene, in a Phase 1/2 clinical trial in people with Gaucher disease type 1. Freeline has additional programs in research, including one focused on GBA1-linked Parkinson’s disease that leverages the same novel transgene as FLT201. Freeline is headquartered in the UK and has operations in the United States. For more information, visit www.freeline.life or connect with Freeline on LinkedIn and Twitter.

SOURCE: Freeline Therapeutics