From Acne to Cancer, BiomX Infects Bad Bacteria with Modified Viruses
Phage therapies are emerging as a solution for conditions from acne to cancer, based on the body’s symbiotic relationship with the bacterial environment. While many microbiome therapies rely on adding bacteria, like probiotics, Israel-based BiomX takes a somewhat unique approach of removing harmful bacteria.
Bacteriophage (phage) is a type of virus that infects only bacteria. Phages were discovered in 1915, but “We’ve only had a grasp of the phage defense mechanism for the past 10 to 15 years,” said Jonathan Solomon CEO and board member of BiomX. “There’s evidence of good and bad bacteria in the body, and it’s clear the presence or absence of bacteria can have major health impacts. At BiomX, we want to pick out specific harmful bacteria in a precise way without affecting the beneficial bacteria.”
BiomX is developing a way to modulate the microbiome to do just that, using cocktails of either natural or engineered phages.
Its most advanced product, a phage-infused topical gel to treat acne, is gearing up for Phase II trials. In Phase I data, after four weeks of treatment with BX001, “We saw significant bacterial load reduction,” Solomon said. The company expects to have a Phase II readout by mid-2021.
Its second program, and one of its most exciting, is designed for inflammatory bowel disease (IBD). “The IBD program targets specific bacteria that drive an inflammatory response in IBD animal models,” Solomon said.
“IBD patients can’t use antibiotics chronically because eradication of the beneficial bacteria in the gut for a long period negatively impacts their immune systems, which exacerbates their symptoms and subsequently makes them feel worse,” Assaf Oron, chief business officer, said at BIO-Europe® last month. “By using phage, you can specifically eradicate the bacteria that are causing the inflammatory response without impacting the healthy biota in the microbiome.”
As Solomon elaborated, “BX003 targets a specific, extremely inflammatory bacteria in the gut that triggers a process that, when it gets out of control, damages the gut. If you could take out that bacteria early, this could be a potential cure. We have initiated a Phase I trial for an oral compound and expect a readout in the first quarter of 2021.”
Building on its IBD work, BiomX is collaborating with Boehringer Ingelheim to develop microbiome-based biomarkers associated with patient phenotypes in IBD. BiomX’s XMarker platform uses a metagenomics approach that combines ultra-high-resolution DNA analysis, artificial intelligence and cloud computing to develop predictive microbial genomic signatures into biomarkers.
Several preclinical programs are in development, too. The company recently presented preclinical results of phage that targeted Klebsiella pneumoniae for the treatment of primary sclerosing cholangitis and IBD at The Liver Meeting 2020. In that study, broad host range phage were shown to eradicate 89% of the Klebsiella pneumoniae in some 1,000 strains taken from 300 patients with either of those two indications.
Its cancer program combines phages with checkpoint inhibitors to enhance the effectiveness of immunotherapies. Currently, “fewer than 10% of colorectal cancer patients are eligible for immunotherapy or checkpoint inhibitors,” Oron said. “That’s because most colorectal cancer tumors are cold” (They do not respond to immunotherapy).
Therefore, BiomX uses phage to target the Fusobacterium nucleatum bacteria, kill it and then release immune stimulating molecules. F. nucleatum is present within approximately 80% of colorectal tumors and appears to contribute to its pathogenesis by cloaking the tumor from the immune system. Preclinical results are expected in the second quarter of 2021.
Additionally, “We started our cystic fibrosis program a couple months ago to address Pseudomonas aeruginosa, the opportunistic pathogen that colonize patients’ lungs. We expect to present results from a clinical proof of concept by the end of 2021,” Solomon said.
BiomX’s atopic dermatitis program also is in its early stages. It targets Staphylococcus aureus, a bacterium linked to the development and exacerbation of inflammation in that condition. Phase II proof of concept data is expected in the first half of 2022.
“Phage have an amplifying lifecycle,” Oron said.
In BiomX’s subtractive approach, they infect specific bacteria cells, multiply, assemble, eradicate their hosts, and repeat the cycle.
“Within approximately half an hour, you have one dead bacteria and hundreds new phages. Within one hour, you have 100 dead bacteria and 10,000 new phages,” Oron said. “They are potent killers, but a given phage would only target a specific bacterial species or strain and will not harm the other bacteria in the microbiome.”
Development time is fast.
“From the time of program initiation, we can generate answers regarding meaningful effects in the clinic within 12 to 18 months, compared to the three to five years it generally takes drugs to get to human studies,” Solomon said.
Such speed is the result of the company’s just-announced BOLT (BacteriOphage Lead to Treatment) platform to rapidly develop and manufacture phage therapeutics, and the willingness of the FDA and other regulators to allow phage therapeutics to often bypass early animal or human studies. Phages are generally recognized as safe, Solomon emphasized, and certain phage have been approved for specific applications as food additives in the U.S. and Europe.
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