The biotech’s crPhage technology works by targeting the DNA of specific bacteria, destroying their cells while leaving non-target bacteria in the human body unaffected.
The deal marks another milestone for Locus on the phage front following its announcement of its US$818M deal with Johnson & Johnson in 2019 and the start of its Phase 1 clinical trial earlier this year.
Cost-reimbursement contract
The Biomedical Advanced Research and Development Authority (BARDA), part US Department of Health and Human Services (HHS), will provide up to US$77m in funding to Locus as part of a US$144m program to support Phase 2 and 3 clinical trials and other activities required to seek marketing approval from the US Food and Drug Administration (FDA) for LBP-EC01.
Joseph Nixon, senior vice president of business development at Locus Biosciences, said the partnership with BARDA is a cost-reimbursement contract. Locus is responsible for all product development work and that agency will reimburse Locus for the majority of the costs incurred. BARDA will also contribute expertise in an advisory capacity, he said.
“We are gaining a substantial amount of funding support that will allow us to take the crPhage program targeting E. coli all the way to the commercial market.”
E. coli threat
LBP-EC01 has dual mechanism of action, utilizing the natural lytic activity of the bacteriophage along with the DNA-targeting activity of CRISPR-Cas3, said Locus.
This dual mechanism makes LBP-EC01 significantly more effective at killing E. coli cells than corresponding natural bacteriophages, as shown both in laboratory tests and in small animal models of urinary tract infection, claims the developer. The mechanism also makes LBP-EC01 effective in killing E. coli strains regardless of whether they are resistant to antibiotics, it added.
Both the US Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have identified antibiotic-resistant E. coli as an urgent and serious public health threat requiring development of new treatments.
Worldwide, an estimated 150 million people are affected by UTIs each year. About 80% of these are caused by E. coli, often including difficult-to-treat strains that are resistant to commonly used antibiotics. Up to 40% of UTI patients experience a recurrence within months of the first episode.
Clinical trials and route to market
Locus initiated its Phase I trial for LBP-EC01 in January 2020, for which it says it expects to complete patient enrollment for that trial within the next 30 to 60 days.
“We anticipate commencing the Phase II trial that is funded under the BARDA collaboration in the summer to fall [Autumn] of 2021,” said Nixon.
What kind of timeline to commercialization does the company anticipate?
“There are a lot of uncertainties in drug development, so it is too early to say for sure when crPhage products will reach the market. However, if all goes well, we anticipate that we could submit a BLA to the FDA for approval as early as 2025 crPhage could be commercially available in 2026,” he told BioPharma-Reporter.
Beyond the urinary tract
Beyond UTI treatment, the company says it is looking to target unmet medical needs in bacterial infections and microbiome indications in oncology, immunology and neuroscience therapeutic areas.
“In collaboration with Johnson & Johnson we are also working on crPhage products targeting two common pathogens that cause infections of the respiratory tract and other body sites.
“Locus also has a robust research program evaluating potential treatments for inflammatory bowel disease, improving patient responses to immune-oncology therapies, fighting infections in patients receiving immune checkpoint inhibitors, and colorectal cancer,” said the product development VP.
Several other companies are developing bacteriophage therapeutics but Nixon said most of them use cocktails of natural or ‘wild-type’ bacteriophages isolated from the environment.
“Locus’s advantage over these competitors is that crPhage are significantly more effective at killing target bacteria compared to their wild-type counterparts. It is also not clear that patents covering wild-type bacteriophage cocktails will provide adequate commercial protection,” he claimed.