Beam Therapeutics Announces Preclinical Data Highlighting Potential of Base Editors to Target Disease Drivers of Chronic Hepatitis B Infection
Beam Therapeutics
Mon, September 27, 2021, 8:30 PM·6 min read
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Data to be Presented During an Oral Presentation at the 2021 International HBV Meeting
CAMBRIDGE, Mass., Sept. 27, 2021 (GLOBE NEWSWIRE) -- Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, today announced preclinical data demonstrating the potential of Beam’s cytosine base editors (CBEs) to reduce viral markers, including hepatitis B surface antigen (HBsAg) expression, and prevent viral rebound of hepatitis B virus (HBV) in in vitro models. These data will be presented today, September 27, 2021, in partnership with Fabien Zoulim’s laboratory at the INSERM Cancer Research Center of Lyon, during an oral presentation titled, “cccDNA Inactivation Using Cytosine Base Editors,” at the 2021 International HBV Meeting.
HBV causes serious liver infection that can become chronic, increasing the risk of developing life-threatening health issues like cirrhosis, liver failure or liver cancer. Chronic HBV infection is characterized by the persistence of covalently closed circular DNA (cccDNA), a unique DNA structure that forms in response to HBV infection in the nuclei of liver cells. Additionally, the HBV DNA integrates into the human genome becoming a source of HBsAg. While currently available treatments can manage HBV replication, they do not clear cccDNA from the infected liver cells. This inability to prevent HBV infection rebound from cccDNA is a key challenge to curing HBV.
Base editors are designed to enable direct and irreversible conversion of a specific DNA base into another without inducing double-stranded breaks. In HBV infected cells, CBEs can target the cccDNA minichromosome at multiple locations, introducing precise and permanent stop codons in the viral genome, which are intended to silence the viral genes without the risk of the chromosomal rearrangements.
“Hepatitis B is a major global health crisis, with more than 250 million people currently diagnosed with chronic disease worldwide. Despite current therapeutic approaches, a key challenge to finding a curative treatment to chronic HBV is being able to prevent infection rebound from cccDNA,” said Giuseppe Ciaramella, Ph.D., president and chief scientific officer of Beam. “The data being presented today show that using our novel CBE, we can directly target and silence cccDNA to significantly reduce relevant HBV viral replicators, without the need to clear cccDNA from the cell. Furthermore, because HBV sequences are extensively integrated in the genome of infected cells, multiplex base editors are a natural fit for permanently silencing HBV genetic elements without creating double-stranded breaks or genetic rearrangements. These data underscore the advantages we believe base editing can offer in treating patients with HBV infection as well as a wide range of serious genetic diseases.”
The results announced today are from a preclinical in vitro study designed to evaluate the potential of base editing to provide a new type of treatment for chronic hepatitis B disease. In the study, infected human hepatoma HepG2-NTCP cells, which are susceptible to HBV infection, and long-term primary human hepatocyte co-cultures, were multiplex edited with selected HBV-targeting gRNAs and mRNA-encoding CBEs. Edits included the introduction of stop codons to reduce HBsAg and HBeAg and silence the HBV gene and the cccDNA. Data findings show that:
Multiplexing two gRNAs designed to introduce stop codons led to substantial, simultaneous reduction of relevant HBV viral markers (HBsAg, HBeAg, HBV DNA, 3.5kb RNA)
Dual gRNA cccDNA-targeting CBE led to 30%-60% editing efficiency of the cccDNA, without reducing cccDNA levels;
Combinatorial treatment of the base editing reagents with standard antiviral lamivudine resulted in 20% higher base editing efficiency leading to high antiviral efficacy; and
Base editing prevented HBV rebound in long-term infected primary hepatocytes.
These results indicate that CBEs can introduce permanent mutations in cccDNA and prevent HBV rebound in relevant in vitro models. Based on these findings, Beam plans to evaluate its base editing approach in relevant in vivo proof of concept models.
About Beam Therapeutics
Beam Therapeutics (Nasdaq: BEAM) is a biotechnology company committed to establishing the leading, fully integrated platform for precision genetic medicines. To achieve this vision, Beam has assembled a platform that includes a suite of gene editing and delivery technologies and is in the process of building internal manufacturing capabilities. Beam’s suite of gene editing technologies is anchored by base editing, a proprietary technology that enables precise, predictable and efficient single base changes, at targeted genomic sequences, without making double-stranded breaks in the DNA. This enables a wide range of potential therapeutic editing strategies that Beam is using to advance a diversified portfolio of base editing programs. Beam is a values-driven organization committed to its people, cutting-edge science, and a vision of providing life-long cures to patients suffering from serious diseases.