Full Press Release Details
We are a clinical-stage biotechnology company focused on precisely
targeted bacteriophage therapeutics for patients with serious and life-threatening antibiotic-resistant bacterial infections. Phages
have a powerful and highly selective mechanism of action that enables them to bind to and kill specific bacteria. We believe that
phages represent a promising means to treat bacterial infections, especially those that have developed resistance to current therapies,
including the so-called multi-drug-resistant or "superbug" strains of bacteria.
We are a leading developer of bacteriophage therapeutics. We
are combining our expertise in the manufacture of drug-quality bacteriophages and our proprietary approach and expertise in identifying,
characterizing and developing naturally occurring bacteriophages to develop state-of-the-art therapeutics. We are developing bacteriophage
products to combat multi- or pan-drug-resistant bacterial pathogens, leveraging advances in sequencing and molecular biology. We
have developed certain bacteriophage combinations that we believe maximize efficacy and minimize development of resistance. We
currently have two product candidates in clinical development, AB-SA01 and AB-PA01 for the treatment of Staphylococcus
aureus, or S. aureus, infections, including methicillin-resistant S. aureus, or MRSA, and Pseudomonas
aeruginosa, or P. aeruginosa, infections, respectively. We intend to develop both product candidates for the treatment
of serious or life-threatening, multi-drug-resistant infections.
We believe our bacteriophage technology may have unique application
in the area of targeted medicine, and in May 2017, we initiated a new strategic emphasis on targeted therapies for serious
or life-threatening antibiotic-resistant infections. In particular, we believe our bacteriophage technology can be used to develop
precisely targeted therapies for patients who suffer from serious or life-threatening antibiotic-resistant bacterial infections
and who have limited or no other satisfactory treatment options. Moreover, we believe our ability to target bacteriophage therapies
for antibiotic-resistant infections, combined with the ability of bacteriophage to disrupt biofilm and having the potential to
re-sensitize drug-resistant populations to antibiotics, represents what could be a powerful tool against the growing global challenge
of antibiotic-resistant infections.
Under existing single-patient expanded access guidelines (also
referred to as "compassionate use"), established by the regulatory agencies, we have provided targeted phage therapies
to patients suffering from severe antibiotic-resistant infections who have failed prior antibiotic therapies. We believe this strategic
approach not only provides potential benefit to patients who have few or no other acceptable therapeutic options, but also generates
the clinical and microbiological data from these cases that we expect to support the potential validation of the clinical utility
of phage therapy, identify the most promising indications for further clinical development of our AB-SA01 and AB-PA01 product
candidates for S. aureus and P. aeruginosa, define optimal treatment regimens, and inform our
discussions with the U.S. Food and Drug Administration, or FDA, and other regulatory agencies in 2018 or later on defining a potential
path to market approval. We are initially making targeted phage therapies available under the appropriate regulatory expanded access
guidelines in the United States and in Australia, where we collaborate with select leading hospitals and key infectious disease
physician opinion leaders to identify eligible patients. We believe that the United States and Australia have favorable regulatory
frameworks and clinical expertise with respect to treating patients under single-patient expanded access guidelines.
Clinical Results for Expanded Access Program
On September 17, 2018, we announced updated topline clinical
results for our ongoing single-patient expanded access program. 84% of patients achieved treatment success (physician's assessment)
at the end of bacteriophage therapy, defined as complete resolution or significant improvement of baseline signs and symptoms.
We have now received clinical outcome results for 21 of the
patents to whom we have provided our investigational bacteriophage therapeutics, at seven hospitals, with serious or life-threatening
infections not responding to antibiotic therapy. Of the 21 patients, 57% were male and 43% were female, and the mean age was 57
years old with patients ranging from 16 years old to 96 years old. These patients were treated with AB-SA01 or AB-PA01, along with
antibiotics, under single-patient expanded access programs in the United States (Emergency INDs, per the FDA) or Australia (Special
Access Scheme, per the Australian Therapeutic Goods Administration).
Through our expanded access program, 15 patients with serious
S. aureus infections were treated with AB-SA01 and six patients with serious P. aeruginosa infections were treated
with AB-PA01. The treated patients' infections included bacteremia and septicemia, native and prosthetic valve endocarditis,
recurrent pneumonia (cystic fibrosis, post-transplant, VAPB), ventilator-associated pneumonia, prosthetic joint infection, ventricular
assist device infection, septicemia due to burns, chronic rhinosinusitis and others. Over 1,000 bacteriophage doses were administered
as part of the expanded access program including, over 400 doses of AB-SA01, of which over 300 doses were administered intravenously.
Treatment of AB-SA01 was well-tolerated in all patients with no treatment-related serious adverse events, or SAEs. Over 600 doses
of AB-PA01 were administered, including over 400 doses administered intravenously. Treatment of AB-PA01 was well-tolerated in five
patients. One patient discontinued treatment of AB-PA01 due to Grade 1 and 2 adverse events, which resolved within 18 hours. There
were no treatment-related SAEs.
Of the patients in the modified intent-to-treat population,
or mITT, 84% (16 out of 19) achieved treatment success at the end of therapy. Treatment success, as determined by the treating
physician, was defined as a complete resolution or significant improvement of baseline signs and symptoms. mITT population was
defined as all patients who met the criteria for clinical diagnosis, whose bacterial isolate was susceptible to phage and who received
at least one dose of phage.
The following chart shows the safety and tolerability results
of our expanded access program:
The following chart shows the clinical outcomes at the end of
therapy of our expanded access program:
The following chart shows the patient disposition from our expanded
AB-SA01 (S. Aureus) Clinical Development Plan
We conducted meetings with the FDA in February 2017 and August
2018 regarding our proposed clinical development of AB-SA01. During the February 2017 meeting with the FDA, we received feedback
on our previously submitted detailed development proposal to commence a Phase 2 trial with AB-SA01 for the treatment of antibiotic-resistant S.
aureus infections in patients with chronic rhinosinusitis. In the official minutes from that meeting, the FDA acknowledged
that phage therapy is an exciting approach for treatment of multi-drug-resistant organisms and expressed a commitment to addressing
the unique regulatory challenges that might arise during product development. In addition, the FDA Center for Biologics Evaluation
and Research stated that the clinical safety and effectiveness data collected during development, including from emergency case
studies, could inform future discussions for clinical development and ultimately, the regulatory pathway to approval. During the
August 2018 meeting with the FDA, which was a Type B pre-IND meeting, we shared the clinical and microbiological results for patients
treated with AB-SA01 under our single-patient expanded access program in 2017 and 2018 and the proposed design of randomized controlled
clinical trials that we developed based on input from key infectious disease physician opinion leaders, in order to establish a
Phase 2 development plan for multiple indications, including bacteremia and prosthetic joint infection.
Based on the FDA's feedback reflected in the official
minutes from the August 2018 Type B pre-IND meeting, we currently plan to initiate the first randomized clinical trial of our AB-SA01
product candidate in early 2019. The clinical trial is expected to enroll approximately 100 patients. The FDA expressed general
agreement with the proposed clinical trial designs, which will be a Phase 1/2 randomized, controlled clinical trial to evaluate
the safety and efficacy of AB-SA01, administered intravenously with the best available antibiotic therapy, compared to placebo
plus best available antibiotic therapy, in approximately 100 patients with S. aureus bacteremia. The second clinical trial
will be a Phase 1/2 randomized, controlled clinical trial to evaluate the safety and efficacy of AB-SA01, administered by intra-articular
injection and then intravenously with the best available antibiotic therapy, compared to placebo plus the best available antibiotic
therapy, in approximately 100 patients with a hip or knee prosthetic joint infection due to S. aureus as an adjunct to surgical
treatment. We intend to produce our proprietary bacteriophage therapeutics for the planned clinical trials at our wholly owned
manufacturing facility, which is good manufacturing practices (GMP) certified by the governmental authorities in the jurisdiction
in which it operates. We believe our GMP-facility has the capacity to produce our proprietary bacteriophage therapeutics for the
planned clinical trials through an anticipated biologics license application filing and potential approval.
Based on the current FDA feedback during the Type B pre-IND
meeting, no additional clinical or nonclinical data are required to proceed with the two proposed randomized clinical trials. Furthermore,
we continue to investigate whether AB-SA01 may be eligible for Fast Track Designation and for approval under the Limited Population
pathway, or LPAD pathway, which is intended to facilitate development of therapeutics to treat serious or life-threatening infections
in a limited population of patients with unmet need. Products eligible for approval under the LPAD pathway may follow streamlined
approaches for clinical development, which may involve smaller, shorter, or fewer clinical trials to help reduce the overall product
development timeline.
AB-PA01 (P. aeruginosa) Clinical Development Plan
In September 2018, we received positive feedback, via written
response, from the FDA regarding our development plans for AB-PA01, without the need for a Type B pre-IND meeting. The FDA expressed