RTP 公司的基因增强抗生素在首个临床试验中取得进展

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经过 艾伦·毛雷尔 

三角研究园 – Locus Biosciences is a step closer to making a new antibiotic that is effective against resistant bacteria available. The company reports that it successfully completed an early, first-of-its-kind clinical trial of its unique antibiotic technology.

The Phase 1b clinical trial of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage (crPhage) precision medicine product targeted Escherichia coli (E. coli) bacteria causing urinary tract infections (UTIs)

The results demonstrated safety and tolerability for LBP-EC01 and help support the overall safety profile for Locus’ phage therapy platform. The trial met all of its primary and secondary endpoints and demonstrated proof of mechanism, as the world’s first completed, randomized, placebo-controlled trial of recombinant bacteriophage therapy.

Bacteriophages are viruses that attack bacteria. They are ubiquitous in the environment and are the most common organisms on the planet, outnumbering bacteria by an estimated 10 to 1.

A COMBINATION APPROACH

Locus’ approach combines the bacteria-hunting activity of bacteriophages with the DNA targeting activity of CRISPR-Cas3. That means the treatment does not harm good bacteria, as it affects only the target.

When a phage targets a bacterial cell, it injects its genetic material into the cell that hijacks the cell’s machinery and uses it to create new copies of itself. The infected bacterium is killed in the process of releasing new phages, which go on to infect additional bacteria.

Locus uses a Cas-3 CRISPR technology that disintegrates DNA rather than just cutting it the way CRISPR Cas-9 does. It’s a bit ironic that the CRISPR technology, which evolved from the way bacteria protect themselves from invaders being used to destroy harmful germs.

In an interview with WRAL TechWire, Dave Ousterout, CFO and co-founder of Locus, said, “CRISPR Cas-3 is a unique system. It targets DNA the way Cas-9 does, but acts differently, and chews up DNA.” In the past, the company has said it’s more like a PacMan than the scissors of Cas-9.

CAS-3 WORLD LEADER

Cas-9 is currently the best known and most used of the CRISPR systems, but Cas-3 is actually used 50 percent of the time in nature.

“We’re a world leader in Cas-3 technology,” Ousterout said.

A new approach to antibiotics is a growing need as germs develop resistance to multiple conventional antibiotics. An alarming rate of increase is projected by United Nations experts who warn that drug-resistant infections could cause 10 million deaths annually by 2050.

The COVID-19 pandemic is further exacerbating the use of antibiotics worldwide, in turn fueling the growth of more drug-resistant bacteria, the company points out.

The Locus technology engineers bacteriophages, which Ousterout notes are “good killers on their own,” to make them even more effective. “It improves the way they work,” he said.

Its first clinical trial focused on UTI, which affect more than 12 million people a year in the US, with a third of those patients being burdened by recurrence. But it has more products in the pipeline and the potential to attract any bacterial infection for which it finds a relevant phage.

ADDITIONAL PRODUCTS IN PIPELINE

“We see the potential to do a lot of things,” Ousterout said.

The company pipeline includes products targeting four of the most common bacterial pathogens. It also has products targeting microbiome-related disorders such as inflammatory bowel disease, pharmaceutical response to immune-oncology therapies, infections associated with immune checkpoint inhibitors and, colorectal cancer. It would eliminate the need for broad-spectrum antibiotics during and after surgery.

Founded in 2015, the 56 person company has iniked a billion dollars in deals. It originated from an idea from a student at North Carolina State University, but was primarily developed at the company. Locus recently closed a debt round that will roll into its next equity round.

Early on, the North Carolina Biotechnology Center provided crucial support. They were one of its instrumental first investors ($830,000 in convertible notes). It later made a strategic investment in the firm.

Locus is preparing for the Phase 2 clinical trial of its UTI product, which will test its effectiveness.

原文来源: WRAL 技术线