The data of the first trial of AAV gene therapy for Crabber disease was released, and there was already a corporate layout in China

September 1, 2022 / Medical McCity News eMedClub News/ -- Recently, Forge Biologics, a biopharmaceutical company focused on gene therapy, released the treatment data of the first patient in the Phase 1/2 RESKUE clinical trial of its research product FBX-101 for Krabbe disease, which initially proved the good efficacy and safety

RESKUE is the first human clinical trial in which subjects receive intravenous injection of FBX-101 after complete bone marrow ablation and cord blood transplantation for systemic AAV gene therapy, and patients do not experience significant adverse reactions within 180 days after injection and are well

FBX-101 is an adeno-associated virus serotype rh10 (AAVrh10) gene therapy for hematopoietic stem cell transplantation that delivers functional copies of the GALAC gene to the central and peripheral nervous systems to prevent the accumulation of galactose cerebrosides in myelin cells in the nervous system, and is intended to be used to treat Krabbe disease

"Krabbe's disease is a rapidly fatal neurodegenerative disease

Different product candidates for the same indications

In addition to FBX-101, a candidate product of Forge Biologics, there are also some companies at home and abroad that have also laid out the same therapeutic field

Passage Bio：PBKR03

Passage Bio is a genetics company focused on the development of treatments for rare, single-gene central nervous system (CNS) diseases
.

Completed a $115.
5 million Series A round in February 2019, another $110 million in Series B financing in September of the same year, and a Passage Bio on the NASDAQ in February 2020
.

PBGM01, PBFT02, PBKR03 are the company's key projects
.

Among them, PBKR03 is an AAV gene therapy in the research and development stage, using the next generation of AAVhu68 capsid to deliver galactose cerebrosidase GLAC gene into the cerebrospinal fluid, using ICM injection (injected into the cerebellar bulbar pool at the cranial-cervical junction) for administration
.

Previously, the U.
S.
Food and Drug Administration (FDA) has awarded PBKR03 fast-track, orphan drug and rare pediatric disease designations; The European Commission has also awarded the drug orphan drug designation
.

In preclinical trials, PBKR03 showed good safety profile in both large and small animal models, with significant improvements in animal Krabbe disease progression and key biomarkers, and no dose-limiting toxicity
was observed.

Currently, patients are being recruited in phase 1/2 clinical trials
of PBKR03.

Lin-2004

Founded in 2019 by Dr.
Han Zhaozhong, the company is committed to developing original platform technology to solve the main problems in the clinical application of biological drugs, and taking such platform technology as the starting point to develop innovative biological drugs with obvious differentiated advantages, better efficacy, more convenient medication and lower drug cost, providing new methods and means for the prevention and treatment of serious chronic diseases
.

In July 2022, it received nearly 100 million yuan of pre-A round financing
.

At present, Lingnuo Pharmaceutical has disclosed 8 pipelines under research
.

Among them, LIN-2004 is an AAV gene therapy under investigation, which is still in the pre-clinical research and development stage
.

How AAV gene therapy is administered

The administration of AAV gene therapy is more diverse, and different methods are selected according to different indications
.

For ophthalmic diseases, most of the AAV gene therapy uses topical administration, including intravitreal injection, subretinal injection, anterior chamber injection, subconjunctival injection, etc
.

Studies have shown that in a variety of animal models, AAV carrier vitreous cavity injection mainly infects ganglion cells, which produces a humoral immune response against AAV capsid protein, causing intraocular inflammation
.

Subretinal injection, on the other hand, which mainly infects retinal pigment epithelial cells and photoreceptor cells, does not trigger a humoral immune response, but there may be bleeding damage caused by the injection and the risk
of potential retinal detachment.

For most other indications, intravenous administration, also known as systemic gene therapy
, is generally chosen.

However, intravenous administration may cause some problems, such as hepatotoxicity
.

After viral products enter the human body, to a certain extent, they will gather in the liver to cause potential hepatotoxicity, and systemic administration often has larger dose requirements, which may cause some dose toxicity
.

But intravenous administration tends to make companies more focused on the safety of
their product candidates.

At present, for AAV gene therapy, the development of more accurate, safe and suitable drug delivery methods is also a major research direction
.

summary

AAV gene therapy is an extremely hot track at the moment, which can give patients the hope
of a one-time cure.

In the future, with the development of related technologies, policy support, and capital investment, AAV gene therapy will show broader application prospects
.

Resources:

1.
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