Research and biotechnology companies have shared developments in phage clinical trials, bringing the potential of accessing phage therapy one step closer. Resistant bacteria are a global problem, and bacteriophages hold so many options towards an effective treatment. In just the last few years, it has been a progressive race amongst companies across the globe, each looking into an innovative approach that will pave the way for phage therapy in the market.
BiomX phase 1a of BX002 phage clinical trial data of first oral phage delivery
BiomX has announced positive results of the phase 1a pharmacokinetic study of BX002 for inflammatory bowel disease and primary sclerosing cholangitis. BX002 was evaluated as an oral delivery of the phage therapy. The data has reflected tolerability and safety with successfully delivering a high concentration of viable bacteriophages to the lower gastrointestinal tract.
“Successful oral delivery of phage therapy, which to our knowledge has now been demonstrated rigorously in a clinical study for the first time, has the potential to open up a broad range of oral phage therapy applications,” commented Timothy K. Lu, M.D., Ph.D., BiomX scientific co-founder, Associate Professor of Biological Engineering, Electrical Engineering and Computer Science, and head of the Synthetic Biology Group in the Research Laboratory of Electronics, at the Massachusetts Institute of Technology.
This is the first clinical study that details pharmacokinetics of oral phage therapy under a US FDA IND protocol. The study involved 18 healthy volunteers who received orally administered BX002. The subjects were randomized to receive either BX002 (n=14) or the placebo (n=4). They received the dose twice daily for a total of three days. All subjects were monitored for seven days with a follow-up of safety assessments performed 14 and 28 days after dose completion. Viable bacteriophages were found in high concentrations in the samples taken from all subjects that received the BX002, in comparison to no levels that were detected of those same participants prior to the phage treatment.
“The results show excellent safety, as expected, and the pharmacokinetics demonstrate the potential to orally administer phage in a quantity sufficient to address the gut bacterial burden of Klebsiella pneumoniae in IBD and PSC patients. In addition, these highly encouraging results highlight the strengths of the BiomX discovery and manufacturing platform and the extremely broad potential of phage technology for addressing challenges in human health.”
Based on the successful results shown by BX002 phase 1a study, BiomX plans in advancing to phase 1b/2a, to study the efficacy of BX003, aimed towards the reduction of Klebsiella pneumoniae. Back in November 2020, BiomX had announced the consolidation of its IBD programme and PSC programme, in order to develop one product candidate that would have a broad host range for both indications, designated as BX003.
Adaptive Phage Therapeutics awarded $5 million for clinical trial 1/2 DANCE
Adaptive Phage Therapeutics has been awarded an additional $5 million from the US Defense Health Agency for the support of the clinical trial against diabetic foot osteomyelitis. Adaptive Phage Therapeutics is on the phase 1/2 DFO Adaptive Novel Care Evaluation (DANCE) to evaluate the safety and efficacy of its precision phage-based therapy.
“We are pleased to announce this expansion of our existing DHA agreement supporting development of phage-based therapies, further highlighting DHA’s commitment to the potential of our adaptive therapeutic approach to improve treatment of a variety of antimicrobial-resistant bacterial infections. This additional $5 million supports our Phase 1/2 DANCE™ clinical trial which is progressing towards generating APT’s first clinical results utilizing our RAPID™ (Rapidly Adaptive Phage for Infectious Disease) technology,” stated Greg Merril, CEO and co-founder of Adaptive Phage Therapeutics.
Initial clinical data from the ongoing phase 1/2 DANCE trial is to be available in the second half of 2023.
The AMR RAPID™ Challenge
Earlier the company had announced The AMR RAPID™ Challenge at the World AMR Congress. Adaptive Phage Therapeutics would pay $1000 to any individual or institution in the clinical research community who identifies a strain of bacteria, within the ESKAPE pathogens, for which the company cannot demonstrate sensitivity to within its phage bank. Applicants of the challenge should contact RAPID@aphage.com for further information, rules, and conditions or visit phagebank.com.
Locus Biosciences phase 2/3 of LBP-EC01 announces first treated patient
Locus Biosciences has announced the treatment of their first patient in the ELIMINATE registrational phase 2/3 trial against urinary tract infections. The company is developing a new class of precision engineered phage treatments for a range of bacterial diseases. ELIMINATE is a registration-enabling phase 2/3 phage clinical trial with the lead candidate LBP-EC01, a CRISPR-enhanced bacteriophage (crPhage®) against urinary tract infections caused by Escherichia coli.
“Interest in exploring bacteriophage therapy for treatment of resistant and recurrent infections. Use of bacteriophages as an alternative or adjunct to conventional antibiotics presents a novel opportunity for tackling recurrent UTIs in an era of increasing antimicrobial resistance,” said Sonali Advani, MBBS, MPH, Assistant Professor of Medicine-Infectious Diseases and board-certified infectious disease physician with extensive research into and clinical experience treating UTIs.
This marks the first randomized phase 2/3 trial of CRISPR-enhanced bacteriophage precision medicine. The study involved LBP-EC01 in combination with commonly used antibiotics. Subjects were female patients with the age between 18-65 who have UTIs caused by multi-drug resistant Escherichia coli. Locus Biosciences now plans to enroll approximately 800 patients across 27 sites across the US and the EU, completing the enrolment in 2024.
“This trial represents a significant milestone for Locus’ CRISPR-Cas3-enhanced bacteriophage, as we work to realize the potential of our precision medicines for bacterial-related diseases, and for the field as this is the first statistically powered registration-enabling trial for a bacteriophage therapy,” said Paul Garofolo, Co-founder and CEO of Locus.
Locus Biosciences has completed phase 1b for LBP-EC01, as the world’s first randomized placebo-controlled trial of recombinant phage therapy. It met all the primary and secondary endpoints and had demonstrated tolerability and safety for LBP-EC01.
Additionally, Johnson & Johnson has backed up Locus Bioscience with $35 million towards the phase2/3 of LBP-EC01. The funding will aid in accelerating the preclinical programmes that are developing therapies for the microbiome-associated conditions, expand the discovery platform engine and boost in-house manufacturing capability to support oral solid dosage delivery.
NIAID and ARLG phage clinical trials evaluating therapy for cystic fibrosis
Antibacterial Resistance Leadership Group (ARLG) will be conducting the trial that is funded by the National Institute of Allergy and Infectious Diseases (NIAID). This study will primarily evaluate the safety of phage therapy and the ability of bacteriophages to reduce the amount of pathogenic bacteria found in the lungs of the volunteers. The experimental phage therapeutic WRAIR-PAM-CF1 was manufactured by Adaptive Phage Therapeutics. WRAIR-PAM-CF1 contains a cocktail of four bacteriophage species that are natural predators of Pseudomonas aeruginosa. The phages have been cultivated, purified and studied extensively in the laboratory setting. Genetic analyses has been carried out to make sure that none of the phages carry any harmful genes that could accidentally be transferred to the target bacteria, such as genes that can confer antibiotic resistance.
“The prevalence of antibiotic resistance is concerning, and the need for more effective therapeutics for vulnerable populations, such as people with cystic fibrosis, is especially urgent,” said NIAID Director Anthony S. Fauci, M.D. “Although research on bacteriophage therapy may still be in its infancy in the United States, we hope that this study, and others like it, could open the doors to a new type of therapy for difficult-to-treat bacterial infections.”
The enrolment for the early-stage clinical trial will evaluate phage therapy against cystic fibrosis in adults, who have the presence of Pseudomonas aeruginosa in their lungs. The study will enroll up to 72 adults from 16 cystic fibrosis centers across the US. The subjects will receive the phage cocktail as a single IV infusion at one of three dosage levels. Researchers will gather data on safety and microbiological activity; how the bacteriophages function in the body, how the cocktail affects the lung function, if the therapy works differently on the pathogen from different geographical regions, and finally, whether the therapy changes the participant’s overall quality of life.
The phage clinical trial will begin at phase 1b and later expand to phase 2. First, two participants per dosage level will receive an unblinded fusion and will be closely monitored for four days. If no serious safety issues are identified, the researchers will begin enrolling additional participants. This stage is double-blinded and the participants will then be assigned, at random, to receive a single fusion at one of the three dosage levels or a placebo fusion. The assessment of the therapy’s safety and microbiological impact will be conducted after eight participants have completed each dosage. This assessment will determine the dosage that will be given in the next stage of the study. The phase 2 trial will enroll up to 50 participants who will be randomly assigned the selected dosage or a placebo. Volunteers will need to have multiple follow-up visits to help monitor the health and reaction to the therapy.