References in this Quarterly Report to "the Company", "BiomX", "we", "us" or
"our", mean BiomX Inc. and its consolidated subsidiaries unless otherwise
expressly stated or the context indicates otherwise. References in this
Quarterly Report to "BiomX Ltd." mean BiomX Ltd., our wholly owned Israeli
subsidiary.
The following discussion and analysis of the Company's financial condition and
results of operations should be read in conjunction with the financial
statements and the notes thereto contained elsewhere in this Quarterly Report.
Certain information contained in the discussion and analysis set forth below
includes forward-looking statements that involve risks and uncertainties.
General
We are a clinical company developing products using both natural and engineered
phage technologies designed to target and destroy bacteria that affect the
appearance of skin, as well as harmful bacteria in chronic diseases, such as
Cystic Fibrosis, or CF, Atopic Dermatitis, or AD, inflammatory bowel disease, or
IBD, primary sclerosing cholangitis, or PSC, and colorectal cancer, or CRC.
Bacteriophage or phage are viruses that target bacteria and are considered inert
to mammalian cells. By developing proprietary combinations of naturally
occurring phage and by creating novel phage using synthetic biology, we develop
phage-based therapies intended to address large-market and orphan diseases.
Since inception in 2015, we have devoted substantially all our resources to
organizing and staffing the company, raising capital, acquiring rights to or
discovering product candidates, developing our technology platforms, securing
related intellectual property rights, and conducting discovery, research and
development activities for our product candidates. We do not have any products
approved for sale, our products are still in the preclinical and clinical
development stages, and we have not generated any revenue from product sales. As
we move our product candidates from preclinical to clinical stage and continue
with clinical trials, we expect our expenses to increase.
Our phage-based product candidates are developed utilizing our proprietary
research and development platform named BOLT. The BOLT platform is unique,
employing cutting edge methodologies and capabilities across disciplines
including computational biology, microbiology, synthetic engineering of phage
and their production bacterial hosts, bioanalytical assay development,
manufacturing and formulation, to allow agile and efficient development of
natural or engineered phage combinations, or cocktails.
BOLT is designed to allow parallel phage cocktail development under two optional
paths:
? A personalized approach aimed at conducting a rapid initial clinical proof of
concept study in patients (Phase 2 results) within approximately 12-18 months
of project initiation. In certain indications the time to clinical proof of
concept may be longer depending on the indication, identity of target
bacteria, recruitment rate, cohort size and other factors. Under this path we
develop an initial phage cocktail or cocktails of naturally-occurring phage
designed to target the bacterial strains isolated from each study subject
participating in the clinical proof of concept study. This phage cocktail or
cocktails may differ from the final optimized phage cocktail to be
commercialized, if approved. The ability to move quickly into clinical
development is also driven by the strong safety profile of naturally-occurring
phage, which we believe will allow us to bypass GLP toxicity studies and
safety studies in healthy volunteers based on feedback from the FDA in
connection with our IBD development program, and to proceed directly to Phase
2 proof of concept.
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? Development of the final optimized fixed phage cocktail to be commercialized -
the optimized cocktail targets a broad patient population and may be comprised
of naturally-occurring or synthetically engineered phage. The cocktail
contains phage with complementary features and is further optimized for
multiple characteristics such as broad target host range, ability to prevent
resistance, biofilm penetration, stability and ease of manufacturing.
Development of the optimized phage cocktail is anticipated to require 1-2
years and will be conducted in parallel to developing the personalized product
candidates and executing the clinical proof of concept studies described
above.
On November 15, 2021, we announced that we plan to focus on CF and AD programs
in 2022 and to temporarily pause the development efforts in IBD and CRC for
approximately one year, as neither program was expected to yield
proof-of-concept data in patients over the next twelve months. In addition, we
decided not to continue to pursue the development plan of our BX001 product
candidate, that was developed to treat acne.
Clinical and Pre-Clinical Developments
Cystic Fibrosis
On March 31, 2021, we announced the selection of the phage cocktail for BX004,
our therapeutic phage product candidate under development for chronic
respiratory infections caused by Pseudomonas aeruginosa, or P. aeruginosa, a
main contributor to morbidity and mortality in patients with CF. Based on
recommendations from the Cystic Fibrosis Therapeutic Development Network, we
updated our Phase 2 proof-of-concept study design and timelines to a Phase 1b/2a
trial in CF patients with chronic respiratory infections caused by P.
aeruginosa. The Phase 1b/2a trial will be comprised of two parts. Part 1 will
evaluate the safety, pharmacokinetics and microbiologic/clinical activity of
BX004 in eight CF patients in a single ascending dose and multiple ascending
dose design. Results from Part 1 are expected in the second quarter of 2022.
Part 2 of the Phase 1b/2a trial will evaluate the safety and efficacy of BX004
in 24 CF patients randomized to a treatment or placebo cohort in a 2:1 ratio.
Results from Part 2 are expected by the third quarter of 2022. In September
2021, BX004 was cleared by the FDA to initiate the Phase 1b/2a trial in CF
patients with chronic respiratory infections caused by P. aeruginosa.
Atopic Dermatitis
On March 31, 2021, we announced the selection of the phage cocktail for BX005,
our topical phage product candidate targeting Staphylococcus aureus, or S.
aureus, a bacterium associated with the development and exacerbation of
inflammation in atopic dermatitis. By reducing S. aureus burden, BX005 is
designed to shift the skin microbiome composition to its "pre-flare" state to
potentially result in clinical improvement. Results from a Phase 2
proof-of-concept trial evaluating the safety and efficacy of BX005 in atopic
dermatitis patients are expected in the third quarter of 2022.
Acne
On October 18, 2021, we announced the results of a Phase 2 cosmetic clinical
study of BX001. The study was a 12-week randomized, single center, double-blind,
placebo-controlled trial in 140 women with mild-to-moderate acne vulgaris.
Subjects were randomized into two cohorts: BX001 or placebo in a 1:1 ratio and
self-administered BX001 or placebo twice daily. Key endpoints from the study
evaluated the safety, tolerability and efficacy of BX001. BX001 was demonstrated
to be safe and well-tolerated with no treatment-related adverse events. A
statistically significant improvement from baseline was observed in appearance
of acne-prone skin but no meaningful difference was demonstrated relative to the
placebo arm of the Study. Significant improvements in the appearance of acne
prone skin, as assessed by reduction in inflammatory lesion counts (48.3%,
p<0.0001), non-inflammatory lesion counts (36.3%, p<0.0001), and by reduction in
average Investigator's Global Assessment, or IGA, score (-0.29, p<0.001), were
observed when compared to baseline for both cohorts. No meaningful difference
was demonstrated for BX001 relative to placebo. As mentioned above, we have
decided not to continue pursuing this program.
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Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
On November 12, 2020, we announced consolidation of our IBD and PSC programs
into a single broad host range product candidate, named BX003, under development
for both indications. Prior to November 2020, we had two separate phage product
candidates for IBD and for PSC, with our IBD product candidate named BX002 and
PSC product candidate named BX003. After the consolidation, the current BX003
product candidate is now under development to treat both IBD and PSC, targeting
bacterial strains of Klebsiella pneumoniae, or K. pneumoniae, a potential
pathogen implicated in both diseases. Prior to the consolidation, our Phase 1a
clinical study was conducted only on BX002, and future clinical studies are
planned to be conducted on BX003 for both IBD and PSC.
On February 2, 2021, we announced positive results of a randomized,
single-blind, multiple-dose, placebo-controlled Phase 1a pharmacokinetic study
of BX002, our product candidate for IBD and PSC, conducted under an
investigational new drug, or IND, application submitted to the FDA. The study
evaluated the safety and tolerability of orally administered BX002 in 18 healthy
volunteers. Subjects were randomized to receive orally either BX002 or placebo,
twice daily for three days. Subjects were monitored for safety for seven days in
a clinical unit, with follow-up monitoring for safety assessments conducted at
14 and 28 days after completion of dosing. BX002 was demonstrated to be safe and
well-tolerated, with no serious adverse events and no adverse events leading to
discontinuation. In addition, the study met its objective of delivering high
concentrations of viable phage to the gastrointestinal tract of approximately
1010 PFU, or plaque forming units. This equals approximately 1,000 times more
viable phage compared to the bacterial burden of K. pneumoniae in IBD and PSC
patients as measured in stool.
Colorectal Cancer
For our CRC program, we are exploring phage mediated delivery of therapeutic
payloads to Fusobacterium nucleatum bacteria residing in the tumors of patients
with colorectal cancer.
For more information regarding our product candidates, see Part I, Item 1
"Business" of our 2020 Annual Report.
COVID-19
On March 12, 2020, the World Health Organization declared COVID-19 a global
pandemic. In an effort to contain and mitigate the spread of COVID-19, many
countries have imposed unprecedented restrictions on travel, mandatory business
closures and other measures designed to mitigate the spread, leading to a
substantial reduction in economic activities in countries around the world,
resulting in certain disruptions to our business throughout 2020 and in 2021.
In response to the pandemic, we have implemented the mandatory as well as
recommended measures to safeguard the health and safety of our employees and
clinical trial participants, and the continuity of our business operations,
including social distancing in our offices, a work from home policy for all
employees who are able to perform their duties remotely and restricting all
nonessential travel, and we expect to continue to take actions as may be
required or recommended by government authorities or as we determine are in the
best interests of our employees, clinical trial participants and others in light
of COVID-19. As of November 10, 2021, COVID-19 has not had a material impact on
our results of operations. However, uncertainty remains as to the potential
impact of COVID-19 on our future research and development activities and the
potential for a material impact on the Company increases the longer the virus
impacts certain aspects of economic activity around the world. The full extent
to which COVID-19 will directly or indirectly impact our business, results of
operations and financial condition, including our ability to fulfill our
clinical trial enrollment needs, will depend on future developments that are
highly uncertain, including as a result of new information that may emerge
concerning COVID-19 and the actions taken to contain it or treat COVID-19, as
well as the economic impact on local, regional, national and international
markets, the ultimate geographic spread of the disease, the duration of the
pandemic, travel restrictions and social distancing in the United States and
other countries, business closures or business disruptions, the ultimate impact
on financial markets and the global economy, the effectiveness of vaccines and
vaccine distribution efforts and the effectiveness of other actions taken in the
United States and other countries to contain and treat the disease. During the
second quarter of 2020, we updated our guidance on the timing of certain
clinical milestones partly due to the health and safety precautions we had taken
and challenges we continue to face in clinical trial enrollment due to COVID-19.
It is not currently possible to predict how long the pandemic will last, what
the long-term global effects will be, or the time that it will take for economic
activity to return to pre-pandemic levels, and we do not yet know the full
impact on our business and operations. We will continue to monitor COVID-19
closely and follow health and safety guidelines as they evolve.
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