Facing tough markets, Freeline Therapeutics drops Fabry disease gene therapy and lays off 30% of workforce

By Jonathan Smith

- Last updated on GMT


Related tags Gene therapy

In an effort to improve its cash runway, the UK biotech company Freeline Therapeutics has paused the development of a gene therapy candidate for the rare metabolic condition Fabry disease. Instead, the company will refocus its efforts on a gene therapy for a different metabolic condition called Gaucher disease.

Freeline announced these decisions in the company’s financial report for 2022​ and corporate update, released this week. The firm also revealed cost-cutting plans to lay off 30% of its workforce.

Pausing Fabry disease gene therapy

Fabry disease​ is part of a group of rare genetic conditions known as lysosomal storage disorders. It is caused by a mutation in a gene encoding an enzyme called alpha-galactosidase A, which breaks down fatty substances in cells. This causes a buildup of these substances in organs including the kidneys, heart, and brain, and can lead to life-threatening organ failure.

Freeline’s gene therapy FLT190 is designed to deliver into Fabry disease sufferers a healthy copy of the gene encoding alpha-galactosidase A, restoring a healthy metabolism in their cells. The candidate, delivered as a one-off infusion, was being tested in a phase 1/2 trial​, and interim results from the first two patients dosed last year indicated that the therapy was well tolerated and helped the patients to produce more alpha-galactosidase A.

However, in spite of this progress, Freeline concluded that its limited resources are better spent on its Gaucher disease gene therapy program, FTL201.

In a business update conference call this week, Michael Parini, CEO of Freeline Therapeutics, said that it was “a difficult decision to pause the program. But given where we are financially in the market conditions, we feel strongly that putting our full weight behind FTL201 is the right decision for Freeline.”

One main gene therapy contender in Fabry disease was AvroBio. AvroBio however, decided to discontinue its phase 2-stage Fabry disease program in January 2022 due to mixed clinical results. Additionally, the US Food and Drug Administration (FDA) granted full approval to the enzyme replacement therapy Fabrazyme, in 2021, making it tougher to develop competing treatments for Fabry disease.

Following the pause of Freeline’s Fabry program, one of the main gene therapies in development is Sangamo Therapeutics’ ST-920, which is undergoing a phase 1/2 trial.

Layoffs and refocusing on Gaucher disease

As it drops the development of FLT190, Freeline will bring its employee workforce down to 65 employees. These layoffs include staff related to FLT190 and across the rest of the organization, intended to streamline the company as it doubles down on FLT201.

Like Fabry disease, Gaucher disease is a lysosomal storage disorder. It is caused by mutations that impair the production of the enzyme beta-glucocerebrosidase, which leads to the harmful buildup of metabolites in multiple organs including the spleen and liver. The condition can be managed with enzyme replacement therapy, but patients require regular infusions in medical facilities, which impacts their quality of life.

Freeline’s FLT201 is a potentially first-in-class gene therapy that involves delivering an engineered copy of the gene encoding glucocerebrosidase. Once delivered into the body, the engineered enzyme is designed to last longer than wild-type versions, which allows it to get to hard-to-reach organs. The candidate is currently in a phase 1/2 trial​ with first results expected in late 2023.

“FLT201 is our greatest potential value driver and our greatest opportunity to benefit patients,” said Parini in a public statement​, adding that the therapy could improve outcomes for patients with a form of the condition called Gaucher disease type 1.

“Gaucher disease type 1 is the most common type of the disease, and despite chronic treatment with current therapies, many patients continue to experience symptoms, including enlarged organs, bone pain, lung dysfunction and low blood counts. We believe one-time treatment with FLT201 could be life-changing.”

Other hopefuls in the race to develop a gene therapy for Gaucher disease include Prevail Therapeutics, owned by Eli Lilly, and AvroBio. Both companies have candidates in phase 1/2 testing.

Shrinking pipeline

Freeline Therapeutics’ pipeline has changed considerably in the last few years. The company had originally been developing gene therapies for the treatment of hemophilia A and B. However, Freeline dropped its hemophilia A candidate in late 2021 and its hemophilia B candidate in late 2022.

According to the company’s latest financial report, Freeline is sitting on $47.3 million as of the end of 2022, compared to $117.7 million as of December 31, 2021. With its restructuring and recent sale of its German subsidiary, Freeline Therapeutics GmbH, the company now expects to stay funded into the second quarter of 2024.

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