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Item 1. Business

2025-03-25 compared with 2024-04-04 · 673 added, 580 removed, 865 unchanged (59% of the section changed)

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with chronic diseases, such as cystic fibrosis, or CF and diabetic foot osteomyelitis, or DFO.

Bacteriophage or phage are bacterial, species-specific,

strain-limited viruses that infect, amplify and kill the target bacteria and are considered inert to mammalian cells.

By utilizing proprietary

combinations of naturally occurring phage and by creating novel phage using synthetic biology, we develop phage-based therapies intended

to address both large-market and orphan diseases.

Based on the urgency of treating the infection (whether acute or chronic),

the susceptibility of the target bacteria to phage (e.g.

the ability to identify a phage cocktail that would target a broad range of bacterial

strains) and other considerations, we offer two phage-based product types:

(1) Fixed cocktail therapy – in this approach a single product containing a fixed number of selected phages is developed to cover

a wide range of bacterial strains, thus allowing treatment of broad patient populations with the same product.

Fixed cocktails are developed

using our proprietary BOLT platform, in which high throughput screening, directed evolution, and bioinformatic approaches are leveraged

to produce an optimal phage cocktail.

(2) Personalized therapy – in this approach a large library of phages is developed, of which single optimal phages are personally

matched to treat specific patients.

Matching optimal phages with patients is carried out using a proprietary phage susceptibility testing,

or PST, where multiple considerations are analyzed simultaneously – allowing for an efficient screen of the phage library while

maintaining short turnaround times.

Bacteriophage or phage are bacterial,

species-specific, strain-limited viruses that infect, amplify and kill the target bacteria and are considered inert to mammalian cells.

By utilizing proprietary combinations of naturally occurring phage and by creating novel phage using synthetic biology, we develop phage-based

therapies intended to address both large-market and orphan diseases.

Based on the urgency of treating the infection

(whether acute or chronic), the susceptibility of the target bacteria to phage (e.g.

the ability to identify a phage cocktail that would

target a broad range of bacterial strains) and other considerations, we offer two phage-based product types:

Fixed cocktail therapy – in this approach a single

product containing a fixed number of selected phages is developed to cover a wide range of bacterial strains, thus allowing treatment

of broad patient populations with the same product.

Fixed cocktails are developed using our proprietary BOLT platform, in which high

throughput screening, directed evolution, and bioinformatic approaches are leveraged to produce an optimal phage cocktail.

Personalized therapy – in this approach a large

library of phages is developed, of which single optimal phages are personally matched to treat specific patients.

Matching optimal

phages with patients is carried out using a proprietary phage susceptibility testing, or PST, where multiple considerations are analyzed

simultaneously – allowing for an efficient screen of the phage library while maintaining short turnaround times.

In our therapeutic programs, we focus on using

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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.

The cocktail contains phage with complementary features and is optimized for multiple characteristics

such as broad target host range, ability to prevent resistance, biofilm penetration, stability and ease of manufacturing.

bacterial hosts, bioanalytical assay development, manufacturing and formulation, to allow agile and efficient development of natural

or engineered phage combinations, or cocktails.

The cocktail contains phage with complementary features and is optimized for multiple

characteristics such as broad target host range, ability to prevent resistance, biofilm penetration, stability and ease of manufacturing.

Our goal is to develop multiple products based

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Our Product Pipeline

below identifies our product candidates’ pipeline, their current status and expected timing for upcoming milestones.

We do not have

any products approved or available for sale, our product candidates are still in the preclinical and clinical development stages, and

we have not generated any revenue from product sales.

The chart below identifies our product candidates’

pipeline, their current status and expected timing for upcoming milestones.

We do not have any products approved or available for sale,

our product candidates are still in the preclinical and clinical development stages, and we have not generated any revenue from product

Ongoing Programs

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-0.28 log (placebo).

This reduction was seen on top of standard of care inhaled antibiotics;

Phage were detected in all patients treated with BX004 during the dosing period, including in several patients up to Day 15 (one week

after end of therapy);

This reduction was seen on top of standard of care inhaled

Phage were detected in all patients treated with BX004 during the dosing period, including in several patients up to Day

15 (one week after end of therapy);

no phage were detected in patients receiving placebo;

there was no evidence of treatment-related resistance to

BX004 during or after treatment , compared to placebo;

and as expected due to the short duration of treatment, there was no detectable

effect on % predicted forced expiratory volume in 1 second, or FEV1.

there was no evidence of treatment-related

resistance to BX004 during or after treatment, compared to placebo;

and as expected due to the short duration of treatment, there was

no detectable effect on % predicted forced expiratory volume in 1 second, or FEV1.

In November 2023, we announced positive topline

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in a 2:1 ratio with 23 CF patients receiving BX004 and 11 patients receiving placebo via nebulization twice daily for 10 days.

Key results from Part 2 of the Phase 1b/2a trial included the following

● Study drug was safe and well-tolerated, with no related SAEs

(serious adverse events) or related APEs (acute pulmonary exacerbations) to study drug.

● In the BX004 arm, 3 out of 21 (14.3%) patients with quantitative

CFU at baseline converted to sputum culture negative for P.

aeruginosa after 10 days of treatment (including 2 patients

after 4 days) compared to 0 out of 10 (0%) in the placebo arm.

placebo showed a positive clinical effect in a predefined

subgroup of patients with reduced baseline lung function (FEV1<70%).

Difference between groups at Day 17:

relative FEV1 improvement

of 5.67% (change from baseline +1.46 vs.

-4.21) and +8.87 points in Cystic Fibrosis Questionnaire-Revised (CFQR) respiratory

symptom scale (change from baseline +2.52 vs.

● In full population, BX004 vs.

aeruginosa levels

were more variable in sputum, potentially driven by aligning initiation of study drug administration with the initiation of standard

of care antibiotic treatment regimen.

In a prespecified subgroup of patients on standard of care inhaled antibiotics on continuous regimen,

Key results from Part 2 of the Phase 1b/2a trial

included the following findings:

Study drug was safe and

well-tolerated, with no related SAEs (serious adverse events) or related APEs (acute pulmonary exacerbations) to study drug.

In the BX004 arm, 3 out

of 21 (14.3%) patients with quantitative CFU at baseline converted to sputum culture negative for P.

aeruginosa after

10 days of treatment (including 2 patients after 4 days) compared to 0 out of 10 (0%) in the placebo arm.

placebo showed

a positive clinical effect in a predefined subgroup of patients with reduced baseline lung function (FEV1<70%).

Difference between

groups at Day 17:

relative FEV1 improvement of 5.67% (change from baseline +1.46 vs.

-4.21) and +8.87 points in Cystic Fibrosis

Questionnaire-Revised (CFQR) respiratory symptom scale (change from baseline +2.52 vs.

In full population, BX004

aeruginosa levels were more variable in sputum, potentially driven by aligning initiation of study

drug administration with the initiation of standard of care antibiotic treatment regimen.

In a prespecified subgroup of patients

on standard of care inhaled antibiotics on continuous regimen, BX004 vs.

placebo reduced sputum P.

aeruginosa levels at Day 10:

difference in change from baseline between groups of -2.8

log10 CFU/g sputum (change from baseline -2.91 vs -0.11), exceeding Part 1 results.

● Alternating/cycling background antibiotic regimen likely associated

with fluctuations in P.

aeruginosa levels potentially confounding the ability to observe a P.

aeruginosa reduction

in this subgroup.

● During the study period, based on current available data,

no evidence of treatment-related phage resistance was observed in patients treated with BX004 compared to placebo.

aeruginosa levels at

difference in change from baseline between groups of -2.8 log10 CFU/g sputum (change from baseline -2.91 vs -0.11),

exceeding Part 1 results.

Alternating/cycling background

antibiotic regimen likely associated with fluctuations in P.

aeruginosa levels potentially confounding the ability

to observe a P.

aeruginosa reduction in this subgroup.

During the study period,

based on current available data, no evidence of treatment-related phage resistance was observed in patients treated with BX004 compared

In August 2023, the FDA granted BX004 Fast Track

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In addition, in December 2023, BX004 received orphan drug designation from the FDA.

BiomX expects to initiate a randomized, double blind, placebo-controlled, multi-center

Phase 2b study in CF patients with chronic P.

aeruginosa pulmonary infections in the fourth quarter of 2024.

The study is designed

to enroll approximately 60 patients randomized at a 2:1 ratio to BX004 or placebo.

Treatment is expected to be administered via inhalation

twice daily for a duration of 8 weeks.

The study is designed to monitor the safety and tolerability of BX004 and is designed to demonstrate

improvement in microbiological reduction of P.

aeruginosa burden and evaluation of effects on clinical parameters such as

lung function measured by FEV1 and patient reported outcomes.

Study results are expected in the third quarter 2025.

BiomX expects to initiate a randomized, double

blind, placebo-controlled, multi-center Phase 2b study in CF patients with chronic P.

aeruginosa pulmonary infections in

the second quarter of 2025.

The study is designed to enroll approximately 60 patients randomized at a 2:1 ratio to BX004 or placebo.

Treatment is expected to be administered via inhalation twice daily for a duration of 8 weeks.

The study is designed to monitor the safety

and tolerability of BX004 and is designed to demonstrate improvement in microbiological reduction of P.

aeruginosa burden

and evaluation of effects on clinical parameters such as lung function measured by FEV1 and patient reported outcomes.

BX004 Phase 2b

topline results are anticipated in the first quarter of 2026.

BiomX has been in communication with the FDA and

additional regulatory agencies regarding the potential to use Real-World Evidence, or RWE, to explore the link between P.

reduction and improved clinical outcomes.

RWE is clinical evidence on the usage, benefits, or risks of a medical product derived from

real-world data, which includes sources such as electronic health records, claims data, patient registries, wearable devices, and observational

We anticipate further discussion with the FDA and European Committee for Medicinal Products for Human Use, or CHMP, in 2025 to

discuss our proposed plan to use RWE to support potential future regulatory filings.

BX211 – Treatment of Diabetic Foot Osteomyelitis (DFO)

BX211 is a personalized phage therapy for the treatment

of DFO associated with Staphylococcus aureus, or S.

The personalized phage treatment tailors a specific phage selected

from a proprietary phage-bank according to the specific strain of S.

BX211 is a phage therapy for the

treatment of DFO associated with Staphylococcus aureus, or S.

The personalized phage treatment tailors a specific

phage selected from a proprietary phage-bank according to the specific strain of S.

aureus biopsied and isolated from each patient.

DFO is a bacterial

infection of the bone that usually develops from an infected foot ulcer and is a leading cause of amputation in patients with diabetes.

We believe that scientific literature demonstrating the potential benefit in treating osteomyelitis using phage in animal models as well

as numerous successful compassionate cases using phage therapy to treat DFO patient support our approach of using phage therapy to treat

The ongoing randomized, double-blind, placebo-controlled,

is a bacterial infection of the bone that usually develops from an infected foot ulcer and is a leading cause of amputation in patients

with diabetes.

We believe that scientific literature demonstrating the potential benefit in treating osteomyelitis using phage in animal

models as well as numerous successful compassionate cases using phage therapy to treat DFO patient support our approach of using phage

therapy to treat DFO.

The randomized, double-blind, placebo-controlled,

multi-center phase 2 study investigating the safety, tolerability, and efficacy of BX211 for subjects with DFO associated with S.

is expected to enroll approximately 45 subjects randomized at a 2:1 ratio to BX211 or placebo.

BX211 or placebo is designed to be administered

weekly, by topical and intravenous, or IV route at week 1 and by the topical route only at each of weeks 2-12.

Over the 12-week treatment

period, all subjects are expected to continue to be treated in accordance with standard of care which will include antibiotic treatment

as appropriate.

A first readout of study topline results is expected at week 13 evaluating healing of the wound associated with osteomyelitis,

followed by a second readout at week 52 evaluating amputation rates and resolution of osteomyelitis based on X-ray, clinical assessments,

and established biomarkers (Erythrocyte Sedimentation Rate, or ESR, and C-Reactive Protein, or CRP).

These readouts are expected in the

first quarter of 2025 and the first quarter of 2026, respectively.

enrolled 41 subjects randomized at a 2:1 ratio to BX211 or placebo.

BX211 or placebo is designed to be administered weekly, by topical

and intravenous, or IV route at week 1 and by the topical route only at each of weeks 2-12.

Over the 12-week treatment period, all subjects

will be treated in accordance with standard of care which includes antibiotic treatment as appropriate.

Readout of study topline results

is expected at week 13 evaluating healing of the wound associated with osteomyelitis, and is expected in the first quarter of 2025.

Non-CF Bronchiectasis, or NCFB

NCFB is a chronic, progressive inflammatory lung

disease characterized by permanent dilation of the bronchi.

Affecting over 1 million diagnosed patients across the US, Europe, and Japan

(according to Weycker, Chron Respir Dis.

2017, Quint, European Respiratory Journal, 2016, Ringshausen, European Respiratory Journal, 2019,

Henkle, Chest, 2018, Asakura, American Journal of Respiratory and Critical Care Medicine 2024, Insmed Commercial Presentation June 4th,

2024), NCFB is caused by multiple etiologies but manifests with similar debilitating symptoms, including chronic cough, sputum production,

and recurrent infections.

aeruginosa infections in NCFB patients are a main contributor to morbidity and mortality in

this disease.

In preclinical in vitro studies, BX004 was shown to be active against antibiotic resistant strains of P.

and demonstrated the ability to penetrate biofilm, an assemblage of surface-associated microbial cells enclosed in an extracellular polymeric

substance and one of the leading causes for antibiotic resistance.

Pending positive data of BX004 in our CF Phase

2b study, we will explore the feasibility of a Phase 2 study in NCFB as an additional indication for BX004.

National Institutes of Health, or NIH study in Cystic Fibrosis

We are supporting a study conducted by the NIH and The Antibacterial

Resistance Leadership Group targeting P.

Aeruginosa infections in CF patients under FDA emergency Investigational New Drug, or

eIND allowance.

The Phase 1b/2, multi-centered, randomized, double-blind, placebo-controlled trial is assessing the safety and microbiological

activity of a single IV dose of bacteriophage therapy in cystic fibrosis subjects colonized with P.

We are supporting a study conducted by the NIH

and The Antibacterial Resistance Leadership Group targeting P.

Aeruginosa infections in CF patients under FDA emergency Investigational

New Drug, or eIND, allowance.

The Phase 1b/2, multi-centered, randomized, double-blind, placebo-controlled trial is assessing the safety

and microbiological activity of a single IV dose of bacteriophage therapy in cystic fibrosis subjects colonized with P.

Programs on hold

BX005 – Treatment of Atopic Dermatitis

BX005 is our topical phage product candidate targeting

Staphylococcus aureus, or S.

aureus , a bacterium associated with the development and exacerbation of inflammation in atopic

aureus is more abundant on the skin of atopic dermatitis patients than on the skin of healthy individuals and

on lesional skin than non-lesional skin.

It also increases in abundance, becoming the dominant bacteria, when patients experience flares.

By reducing the load of S.

aureus , BX005 is designed to shift the skin microbiome composition to its ‘pre-flare’

state and potentially provide a clinical benefit.

In preclinical in vitro studies, BX005 was shown to eradicate over 90% of strains,

including antibiotic resistant strains, from a panel of S.

aureus strains (120 strains isolated from skin of subjects from the

On April 8, 2022, the FDA approved the Company’s IND application for BX005.

As of the date of this Annual Report, we have paused

development efforts for BX005 due to prioritizing resources towards our CF and DFO programs, and we cannot provide guidance on resuming

its development.

Prosthetic Joint Infections, or PJI

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of this program due to prioritizing resources towards our CF and DFO programs, and we cannot provide guidance on resuming its development.

Discontinued programs

BX005 – Treatment of Atopic Dermatitis , or AD

BX005 is our topical phage product candidate targeting

Staphylococcus aureus, or S.

aureus , a bacterium associated with the development and exacerbation of inflammation in AD.

aureus is more abundant on the skin of AD patients than on the skin of healthy individuals and on lesional skin than non-lesional

It also increases in abundance, becoming the dominant bacteria, when patients experience flares.

By reducing the load of S.

aureus , BX005 is designed to shift the skin microbiome composition to its ‘pre-flare’ state and potentially provide a

clinical benefit.

In preclinical in vitro studies, BX005 was shown to eradicate over 90% of strains, including antibiotic resistant

strains, from a panel of S.

aureus strains (120 strains isolated from skin of subjects from the U.S.

2022, the FDA approved the Company’s Investigational New Drug, or IND, application for BX005.

In 2024, we discontinued the development of BX005,

choosing instead to focus our resources on our Cystic Fibrosis and DFO programs.

Our goal is to develop multiple products based

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and efficacy of our lead phage-based product candidates to treat CF and DFO;

Identify new pathogenic bacteria to be targeted by phage therapy for our existing indications and possible new indications;

Develop and partner microbiome-based biomarker tests, based on our proprietary XMarker platform, that can be used for disease diagnosis or as companion diagnostics.

Identify new pathogenic bacteria to be targeted by

phage therapy for our existing indications and possible new indications;

Develop and partner microbiome-based biomarker tests,

based on our proprietary XMarker platform, that can be used for disease diagnosis or as companion diagnostics.

Our phage discovery platform

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that the presence of specific harmful bacteria may impact chronic diseases, such as CF, making them in principle, amenable to treatment

and by a growing number of anecdotal reports from different academic centers of successful compassionate use of phage to treat

seriously ill patients who were unresponsive to other therapies.

and by a growing number of anecdotal reports from different academic centers of successful compassionate use of phage to

treat seriously ill patients who were unresponsive to other therapies.

We believe our phage therapeutic product candidates have the potential

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These cocktails may be comprised of naturally-occurring or synthetically engineered phage.

contains phage with complementary features and is optimized for multiple characteristics such as broad target host range, ability to prevent

resistance, biofilm penetration, stability and ease of manufacturing.

Pre-clinical development of the optimized phage cocktail is anticipated

to require 1-2 years.

contains phage with complementary features and is optimized for multiple characteristics such as broad target host range, ability to

prevent resistance, biofilm penetration, stability and ease of manufacturing.

Pre-clinical development of the optimized phage cocktail

is anticipated to require 1-2 years.

We combine multiple technologies that originate

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Engineering and Computer Science and the Department of Biological Engineering at the Massachusetts Institute of Technology.

addition, through the acquisition of the privately held Israel-based company, RondinX Ltd.

in 2017, we gained access to high throughput

genomic analyses techniques developed by Professor Eran Segal, a leading computational biologist from the Department of Computer Science

and Applied Mathematics at the WIS.

through the acquisition of the privately held Israel-based company, RondinX Ltd.

in 2017, we gained access to high throughput genomic

analyses techniques developed by Professor Eran Segal, a leading computational biologist from the Department of Computer Science and

Applied Mathematics at the WIS.

The combination of the technologies and expertise from these leaders in each of their respective fields

is critical in enabling us to focus on treating complex human diseases and conditions by precise manipulation of the microbiome.

Additionally, we developed proprietary assays and

screening technology for robust and high throughput testing PST.

The PST platform combines state of the art automation with advanced microbiology

The output is a reproducible conclusive decision for optimal phage matching, based on multiple factors, including success of phage

infection, suppression of resistant mutants, and antibiofilm activity.

Additionally, we developed proprietary assays

and screening technology for robust and high throughput testing PST.

The PST platform combines state of the art automation with advanced

microbiology assays.

The output is a reproducible conclusive decision for optimal phage matching, based on multiple factors, including

success of phage infection, suppression of resistant mutants, and antibiofilm activity.

Manufacturing

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Both facilities

are designed to produce clinical quantities of our product candidates required for early-stage clinical development with compliance suitable

for this stage of development and to support eIND.

The Ness Ziona facility consists of two suites

for drug substance phage production/development as well as formulation and final drug product production rooms to support topical, oral,

inhaled and injectable phage-based products in a liquid, cream, semi-solid or dry form.

The Gaithersburg facility consists of three manufacturing

suites, one for upstream seed banking, one for drug substance phage production, and one for formulation and fill of the final drug product.

This facility is also equipped with in-house quality control testing laboratories to support the release of injectable phage-based products

in a liquid form.

Additional laboratory space is allocated for process development and there are laboratory and office spaces available

that can be repurposed for future GMP expansion.

were designed to produce clinical quantities of our product candidates required for early-stage clinical development with compliance

suitable for this stage of development and to support eIND.

Currently, our use of these 2 facilities for GMP manufacturing has been put

on hold while our in-house development activities continue to support our projects in other ways.

The Ness Ziona facility, which has currently been

put on hold but can resume GMP manufacturing, consists of two suites for drug substance phage production/development as well as formulation

and final drug product production rooms to support topical, oral, inhaled and injectable phage-based products in a liquid, cream, semi-solid

We no longer expect to use our Gaithersburg facility for manufacturing.

We currently operate a manufacturing model that

combines in-house process development, manufacturing and testing with the flexibility to outsource to third-party development, manufacturing,

testing, and logistics organizations, when needed.

We maintain service agreements with multiple manufacturers, testing laboratories and

a third-party logistics warehouse for product candidate distribution.

These service agreements are generally short-term in nature and

can be extended or renewed.

combines in-house process development and testing with the flexibility to outsource to third-party development, manufacturing, testing,

and logistics organizations, when needed.

We maintain service agreements with multiple manufacturers, testing laboratories and a third-party

logistics warehouse for product candidate distribution.

These service agreements are generally short-term in nature and can be extended

As such, for BX004, we have engaged a third-party to supplement our in-house process development activities.

We selected this organization based on its experience, capability, capacity and regulatory status.

Manufacturing and development projects

are managed by a team of internal staff who assure compliance with the technical aspects and regulatory requirements of the manufacturing

Additional phage bank product candidates collectively

known as BX211 are manufactured at our in-house GMP facility in Gaithersburg.

Such product candidates are produced and released by internal

staff in compliance with cGMPs.

We perform release testing in house for most release assays and also outsource testing to qualified laboratories.

In addition, we utilize a third-party logistics warehouse for product storage and distribution to clinical sites.

We are considering consolidation of the two GMP

sites into one based on future needs.

While we do not have a current need for a commercial scale manufacturing capacity, at the appropriate

time we intend to evaluate building large scale cGMP internal manufacturing capabilities, which may include expansion of our operations.

this organization based on its experience, capability, capacity and regulatory status.

Manufacturing and development projects are managed

by a team of internal staff who assure compliance with the technical aspects and regulatory requirements of the manufacturing process.

While we do not have a current need for a commercial

scale manufacturing capacity, at the appropriate time we intend to evaluate building large scale cGMP internal manufacturing capabilities,

which may include expansion of our operations.

Intellectual Property

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innovation and in-licensing opportunities to develop and maintain our proprietary position.

For more information regarding the risks related

to our intellectual property, see “ Risk Factors — Risks Related to our Licensed and Co-Owned Intellectual Property.

For more information regarding the risks

related to our intellectual property, see “ Risk Factors — Risks Related to our Licensed and Co-Owned Intellectual Property.

We plan to continue to expand our intellectual

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Patent portfolio

Our patent portfolio consists of owned patent applications,

as well as both licensed and co-owned patent applications (that are also licensed).

See “ Risk Factors — Risks Related to

our Licensed and Co-Owned Intellectual Property.

” For some of these applications, prosecution has not started, and others are

in the early stages of prosecution in the United States and in selected jurisdictions outside of the United States.

We solely own four

patent families.

We co-own one US patent family with Keio University in Tokyo, Japan, or Keio, one international patent family (United

States, Australia, Canada, European Patent Office national filings) with Yeda Research and Development Company Limited, the technology

transfer office of the WIS, or Yeda, and one international patent family (United States, Europe) with both Keio and Yeda.

We have an exclusive

license from Yeda and Keio for these co-owned patent applications.

We have exclusive licenses from Yeda or Keio for the rest of the patents

and patent applications in its portfolio.

Our patent portfolio consists of owned patent

applications, as well as both licensed and co-owned patent applications (that are also licensed).

See “ Risk Factors —

Risks Related to our Licensed and Co-Owned Intellectual Property.

” For some of these applications, prosecution has not started,

and others are in the early stages of prosecution in the United States and in selected jurisdictions outside of the United States.

solely own eight patent families.

We co-own one US patent family with Keio University in Tokyo, Japan, or Keio, one international patent

family (United States, Australia, Canada, European Patent Office national filings) with Yeda Research and Development Company Limited,

the technology transfer office of the WIS, or Yeda, and one international patent family (United States, Europe) with both Keio and Yeda.

We have an exclusive license from Yeda and Keio for these co-owned patent applications.

We have exclusive licenses from Yeda or Keio

for the rest of the patents and patent applications in its portfolio.

A significant portion of our portfolio is directed

to our product candidates, specifically:

CF and atopic dermatitis as well as product candidates relevant to programs which we have stopped

their development such as:

inflammatory bowel disease, or IBD, primary sclerosing cholangitis and colorectal cancer, or CRC, as well as

to our bacterial target discovery and bacteriophage discovery technology platforms.

Prosecution has yet to commence for most of the pending

patent applications covering our product candidates.

Prosecution is a lengthy process, during which the scope of the claims initially

submitted for examination by the USPTO are often significantly narrowed by the time they issue, if they issue at all.

We expect this to

be the case with respect to our licensed and co-owned patent applications, described briefly below.

to CF, as well as product candidates relevant to programs which we have stopped their development such as:

AD, inflammatory bowel disease,

or IBD, primary sclerosing cholangitis and colorectal cancer, or CRC, as well as to our bacterial target discovery and bacteriophage

discovery technology platforms.

Prosecution has yet to commence for most of the pending patent applications covering our product candidates.

Prosecution is a lengthy process, during which the scope of the claims initially submitted for examination by the USPTO are often significantly

narrowed by the time they issue, if they issue at all.

We expect this to be the case with respect to our licensed and co-owned patent

applications, described briefly below.

In connection with the Acquisition, we further

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South Africa).

APT’s patents and patent applications consist of patents and patent applications with respect to pharmaceutical compositions

and methods of treatment, methods of manufacture of such compositions and expire between June 2037 and October 2043.

We solely own one patent family (United States,

Australia, Canada, European Patent Office, Japan and China) containing claims directed to pharmaceutical compositions comprising combinations

of bacteriophage to treat chronic Pseudomonas lung infections, especially common in CF patients, methods of use for these bacteriophage

combinations, and methods of identifying patients who will respond to these bacteriophage combinations.

Any United States patents issuing

from the pending application covering our lead bacteriophage combination in this program, if issued, are expected to expire in 2042.

term adjustments or patent term extensions could result in later expiration dates.

Atopic Dermatitis

APT’s patents and patent applications consist of patents and patent applications with respect to pharmaceutical

compositions and methods of treatment, methods of manufacture of such compositions and expire between June 2037 and October 2043.

We solely own two patent families (one at pre-PCT

stage and a second in national phase stage in United States, Australia, Canada, European Patent Office, Japan and China) containing claims

directed to pharmaceutical compositions comprising combinations of bacteriophage to treat chronic Pseudomonas lung infections, especially

common in CF patients, methods of use for these bacteriophage combinations, and methods of identifying patients who will respond to these

bacteriophage combinations.

Any United States patents issuing from the pending application covering our lead bacteriophage combination

in this program, if issued, are expected to expire in 2042.

Patent term adjustments or patent term extensions could result in later expiration

We solely own one patent family (United States,

Australia, Canada, European Patent Office and Japan) containing claims directed to pharmaceutical compositions comprising combinations

of bacteriophage to treat skin infections, especially common in atopic dermatitis patients, methods of use for these bacteriophage combinations,

and methods of identifying patients who will respond to these bacteriophage combinations.

Any United States patents issuing from the pending

application covering our lead bacteriophage combination in this program, if issued, are expected to expire in 2042.

Patent term adjustments

or patent term extensions could result in later expiration dates.

of bacteriophage to treat staphylococcus aureus infections, common in patients with DFO and in AD patients, methods of use for these

bacteriophage combinations, and methods of identifying patients who will respond to these bacteriophage combinations.

Any United States

patents issuing from the pending application covering our lead bacteriophage combination in this program, if issued, are expected to

expire in 2042.

Patent term adjustments or patent term extensions could result in later expiration dates.

The term of individual patents depends upon the

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patent cannot be extended more than once or for more than a single product.

During the period of extension, if granted, the scope of exclusivity

is limited to the approved product for approved uses.

Some foreign jurisdictions, including Europe and Japan, have analogous patent term

extension provisions, which allow for extension of the term of a patent that covers a drug approved by the applicable foreign regulatory

During the period of extension, if granted, the scope of

exclusivity is limited to the approved product for approved uses.

Some foreign jurisdictions, including Europe and Japan, have analogous

patent term extension provisions, which allow for extension of the term of a patent that covers a drug approved by the applicable foreign

regulatory agency.

In the future, if and when our product candidates

receive FDA approval, we expect to apply, if appropriate, for patent term extension on patents directed to those product candidates, their

methods of use and/or methods of manufacture.

However, there is no guarantee that the applicable authorities, including the FDA in the

United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions.

receive FDA approval, we expect to apply, if appropriate, for patent term extension on patents directed to those product candidates,

their methods of use and/or methods of manufacture.

However, there is no guarantee that the applicable authorities, including the FDA

in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length of such

Trade Secrets and Know-How

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and know-how to develop and maintain our competitive position.

We typically rely on trade secrets to protect aspects of our business that

are not amenable to, or that we do not consider appropriate for, patent protection.

We typically rely on trade secrets to protect aspects of our business

that are not amenable to, or that we do not consider appropriate for, patent protection.

We protect trade secrets and know-how by establishing

confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors and collaborators.

These agreements provide that all confidential information developed or made known during the course of an individual’s or entities’

relationship with us must be kept confidential during and after the relationship.

These agreements also provide that all inventions resulting

from work performed for us or relating to our business and conceived or completed during the period of employment or assignment, as applicable,

shall be our exclusive property.

In addition, we take other appropriate precautions, such as physical and technological security measures,

to guard against misappropriation of its proprietary information by third parties.

confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors and

collaborators.

These agreements provide that all confidential information developed or made known during the course of an individual’s

or entities’ relationship with us must be kept confidential during and after the relationship.

These agreements also provide that

all inventions resulting from work performed for us or relating to our business and conceived or completed during the period of employment

or assignment, as applicable, shall be our exclusive property.

In addition, we take other appropriate precautions, such as physical and

technological security measures, to guard against misappropriation of its proprietary information by third parties.

Although we take steps to protect our proprietary

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While we believe that

our technology, knowledge and experience provide us with competitive advantages, we face substantial competition from many different sources,

including larger pharmaceutical companies with more resources.

Specialty biotechnology companies, academic research institutions, governmental

agencies, as well as public and private institutions are also potential sources of competitive products and technologies.

We believe that

the key competitive factors affecting the success of any of our product candidates will include efficacy, safety profile, time to market,

cost, level of promotional activity and intellectual property protection.

our technology, knowledge and experience provide us with competitive advantages, we face substantial competition from many different

sources, including larger pharmaceutical companies with more resources.

Specialty biotechnology companies, academic research institutions,

governmental agencies, as well as public and private institutions are also potential sources of competitive products and technologies.

We believe that the key competitive factors affecting the success of any of our product candidates will include efficacy, safety profile,

time to market, cost, level of promotional activity and intellectual property protection.

We are aware of a number of biotechnology companies

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occurring phage or synthetic biology approaches.

In addition, we are aware of several investigational and marketed products to treat the

indications that we are targeting with our product candidates, including, but not limited to:

In addition, we are aware of several investigational and marketed products to treat

the indications that we are targeting with our product candidates, including, but not limited to:

Trikafta, Symdeco,

Pulmozyme, Tobramycin, Aztreonam

TP-102 being developed

by Technophage, a phage-based product being developed by Phaxiam

Many of our competitors, either alone or with their

strategic partners, have substantially greater financial, technical and human resources than ours and significantly greater experience

developed by Technophage, a phage-based product being developed by Phaxiam

Many of our competitors, either alone or with

their strategic partners, have substantially greater financial, technical and human resources than ours and significantly greater experience

in the discovery and development of product candidates, obtaining FDA and other regulatory approvals of products and the commercialization

of those products.

Accordingly, our competitors may be more successful than us in discovering product candidates, obtaining approval for

such product candidates and achieving widespread market acceptance.

Our competitors’ products may be more effective, or more effectively

marketed and sold, than any product we may commercialize and may render our product candidates obsolete or non-competitive before we can

recover the expenses of developing and commercializing any of our product candidates.

We anticipate that we will face intense and increasing

competition as new drugs enter the market and advanced technologies become available.

Accordingly, our competitors may be more successful than us in discovering product candidates, obtaining approval

for such product candidates and achieving widespread market acceptance.

Our competitors’ products may be more effective, or more

effectively marketed and sold, than any product we may commercialize and may render our product candidates obsolete or non-competitive

before we can recover the expenses of developing and commercializing any of our product candidates.

We anticipate that we will face intense

and increasing competition as new drugs enter the market and advanced technologies become available.

These third parties compete with us in recruiting

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Sales and Marketing

to pursue the commercialization of our drug product candidates either by building internal sales and marketing capabilities or through

collaborations with others.

2021, we entered into a stock purchase agreement with a subsidiary of Maruho, a leading dermatology-focused pharmaceutical company in

Japan, pursuant to which we issued to Maruho 375,000 shares of Common Stock, at a price of $8.00 per share for gross proceeds of $3 million.

We also granted Maruho a right of first offer to license our BX005 product candidate for atopic dermatitis in Japan.

The right of first

offer will commence following the availability of results from a the Phase 1/2 study which is currently on hold.

We intend to pursue the commercialization of our

drug product candidates either by building internal sales and marketing capabilities or through collaborations with others.

Government Regulation

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Generally, before a new drug or biologic can be studied in human clinical trials or marketed, considerable

data demonstrating its quality, safety, efficacy, purity, and/or potency must be obtained, organized into a format specific for each regulatory

authority, submitted for review and approved by the regulatory authority where the product is intended to be studied or marketed.

data demonstrating its quality, safety, efficacy, purity, and/or potency must be obtained, organized into a format specific for each

regulatory authority, submitted for review and approved by the regulatory authority where the product is intended to be studied or marketed.

Biological Product Development Process

In the United States, the FDA regulates drugs under

the Federal Food, Drug, and Cosmetic Act, or the FDCA, and its implementing regulations under the FDCA, the Public Health Service Act,

or the PHSA, and their implementing regulations.

In the United States, the FDA regulates drugs

under the Federal Food, Drug, and Cosmetic Act, or the FDCA, and its implementing regulations under the FDCA, the Public Health Service

Act, or the PHSA, and their implementing regulations.

Both drugs and biologics are also subject to other federal, state and local statutes

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Any agency or judicial enforcement action could have a material adverse effect on us.

Certain of our current product candidates and future

product candidates must be approved by the FDA through a Biologics License Application, or BLA, process before they may be legally marketed

in the United States.

Certain of our current product candidates and

future product candidates must be approved by the FDA through a Biologics License Application, or BLA, process before they may be legally

marketed in the United States.

The process generally involves the following.

Completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with GLP requirements, if needed;

Submission to the FDA of an IND, which must become effective before human clinical trials may begin;

Approval by an institutional review board, or IRB, at each clinical trial site before each trial may be initiated;

Performance of adequate and well-controlled human clinical trials in accordance with applicable IND regulations, good clinical practice, or GCP, requirements and other clinical trial-related regulations to establish the safety, purity, potency and efficacy of the investigational product for each proposed indication;

However, the new Trump administration may change or overhaul

existing drug regulations, which would lead to additional time and money to comply with:

Completion of extensive preclinical studies in accordance

with applicable regulations, including studies conducted in accordance with GLP requirements, if needed;

Submission to the FDA of an IND, which must become

effective before human clinical trials may begin;

Approval by an institutional review board, or IRB,

at each clinical trial site before each trial may be initiated;

Performance of adequate and well-controlled human clinical

trials in accordance with applicable IND regulations, good clinical practice, or GCP, requirements and other clinical trial-related

regulations to establish the safety, purity, potency and efficacy of the investigational product for each proposed indication;

Submission to the FDA of a BLA;

A determination by the FDA within 60 days of its receipt of a BLA to accept the application for review;

Satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the biologic will be produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the biologic’s identity, strength, quality and purity;

Potential FDA audit of the clinical trial sites that generated the data in support of the BLA;

Payment of user fees for FDA review of the BLA (unless a fee waiver applies);

FDA review and approval of the BLA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the biologic in the United States.

A determination by the FDA within 60 days of its receipt

of a BLA to accept the application for review;

Satisfactory completion of an FDA pre-approval inspection

of the manufacturing facility or facilities where the biologic will be produced to assess compliance with cGMP requirements to assure

that the facilities, methods and controls are adequate to preserve the biologic’s identity, strength, quality and purity;

Potential FDA audit of the clinical trial sites that

generated the data in support of the BLA;

Payment of user fees for FDA review of the BLA (unless

a fee waiver applies);

FDA review and approval of the BLA, including consideration

of the views of any FDA advisory committee, prior to any commercial marketing or sale of the biologic in the United States.

Preclinical Studies and IND

Preclinical studies include laboratory evaluation

of product chemistry and formulation, as well as in vitro and animal studies to establish a rationale for therapeutic use and in

some cases to assess the potential for adverse events.

of product chemistry and formulation, as well as in vitro and animal studies to establish a rationale for therapeutic use and

in some cases to assess the potential for adverse events.

The conduct of preclinical studies is subject to federal regulations and requirements,

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concerns or questions related to one or more proposed clinical trials and places the trial on clinical hold.

In such a case, the IND sponsor

and the FDA must resolve any outstanding concerns before the clinical trial can begin.

As a result, submission of an IND may not result

in the FDA allowing clinical trials to commence.

In such a case, the IND

sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

As a result, submission of an IND may

not result in the FDA allowing clinical trials to commence.

Clinical Trials

Clinical trials involve the administration of the

drug or biological product candidate to healthy volunteers or disease-affected patients under the supervision of qualified investigators,

Clinical trials involve the administration of

the drug or biological product candidate to healthy volunteers or disease-affected patients under the supervision of qualified investigators,

generally physicians not employed by, or under, the trial sponsor’s control.

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Information about certain clinical

trials, including clinical trial results, must be submitted within specific timeframes for publication on the www.clinicaltrials.gov website.

trials, including clinical trial results, must be submitted within specific timeframes for publication on the www.clinicaltrials.gov

Clinical trials generally are conducted in three

sequential phases, known as Phase 1, Phase 2 and Phase 3, and may overlap.

Phase 1 clinical trials generally involve a small number of healthy volunteers or disease-affected patients who are initially exposed to a single dose and then multiple doses of the product candidate.

The primary purpose of these clinical trials is to assess the metabolism, pharmacologic action, side effect tolerability and safety of the product candidate.

Phase 2 clinical trials generally involve studies in disease-affected patients to evaluate proof of concept and/or determine the dosing regimen(s) for subsequent investigations.

At the same time, safety and sometimes further pharmacokinetic and pharmacodynamic information is collected, possible adverse effects and safety risks are identified and a preliminary evaluation of efficacy is conducted.

Phase 3 clinical trials generally involve a large number of patients at multiple sites and are designed to provide the data necessary to demonstrate the effectiveness of the product for its intended use, its safety in use and to establish the overall benefit/risk relationship of the product and provide an adequate basis for labeling for new drugs.

Phase 1 clinical trials generally involve a small number

of healthy volunteers or disease-affected patients who are initially exposed to a single dose and then multiple doses of the product

The primary purpose of these clinical trials is to assess the metabolism, pharmacologic action, side effect tolerability

and safety of the product candidate.

Phase 2 clinical trials generally involve studies in

disease-affected patients to evaluate proof of concept and/or determine the dosing regimen(s) for subsequent investigations.

same time, safety and sometimes further pharmacokinetic and pharmacodynamic information is collected, possible adverse effects and

safety risks are identified and a preliminary evaluation of efficacy is conducted.

Phase 3 clinical trials generally involve a large number

of patients at multiple sites and are designed to provide the data necessary to demonstrate the effectiveness of the product for

its intended use, its safety in use and to establish the overall benefit/risk relationship of the product and provide an adequate

basis for labeling for new drugs.

Post-approval trials, sometimes referred to as

Phase 4 clinical trials, may be conducted after initial marketing approval.

These trials are conducted to gain additional experience from

the treatment of patients in the intended therapeutic indication.

These trials are conducted to gain additional experience

from the treatment of patients in the intended therapeutic indication.

In certain instances, the FDA may mandate the performance of Phase

4 clinical trials as a condition of approval of a BLA.

Progress reports detailing the results of the clinical

trials, among other information, must be submitted at least annually to the FDA and written IND safety reports must be submitted to the

FDA and the investigators for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing

that suggest a significant risk for human subjects and any clinically important increase in the rate of a serious suspected adverse reaction

over that listed in the protocol or investigator brochure.

Progress reports detailing the results of the

clinical trials, among other information, must be submitted at least annually to the FDA and written IND safety reports must be submitted

to the FDA and the investigators for serious and unexpected suspected adverse events, findings from other studies or animal or in

vitro testing that suggest a significant risk for human subjects and any clinically important increase in the rate of a serious suspected

adverse reaction over that listed in the protocol or investigator brochure.

It is possible for Phase 1, Phase 2, Phase 3 and

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or terminate a clinical trial at any time on various grounds, including a finding that the patients are being exposed to an unacceptable

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being

conducted in accordance with the IRB’s requirements or if the biologic has been associated with unexpected serious harm to patients.

Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor,

or the Data Safety Monitoring Board.

This group provides authorization for whether a trial may move forward at designated check points

based on access to certain data from the trial.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not

being conducted in accordance with the IRB’s requirements or if the tested biological product has been associated with unexpected

serious harm to patients.

Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the

clinical trial sponsor, or the Data Safety Monitoring Board.

This group provides authorization for whether a trial may move forward at

designated check points based on access to certain data from the trial.

Concurrent with clinical trials, companies may

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the regulatory requirements for potency and purity.

The results of preclinical studies and clinical trials are then submitted to the FDA

as part of a BLA, along with proposed labeling, chemistry and manufacturing information to ensure product quality and other relevant data.

The BLA is a request for approval to market the biologic for one or more specified indications and must contain proof of safety, purity

The application may include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive

Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from

a number of alternative sources, including studies initiated by investigators.

To support marketing approval, the data submitted must

be sufficient in quality and quantity to establish the safety and efficacy in the intended indication, purity and potency of the investigational

product to the satisfaction of the FDA.

FDA approval of a BLA must be obtained before a biologic may be marketed in the United States.

The results of preclinical studies and clinical trials are then submitted to the

FDA as part of a BLA, along with proposed labeling, chemistry and manufacturing information to ensure product quality and other relevant

The BLA is a request for approval to market the biological product for one or more specified indications and must contain proof

of safety, purity and potency.

The application may include both negative and ambiguous results of preclinical studies and clinical trials,

as well as positive findings.

Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s

use or from a number of alternative sources, including studies initiated by investigators.

To support marketing approval, the data submitted

must be sufficient in quality and quantity to establish the safety and efficacy in the intended indication, purity and potency of the

investigational product to the satisfaction of the FDA.

FDA approval of a BLA must be obtained before a biologic may be marketed in the

United States.

Under the Prescription Drug User Fee Act, or PDUFA, as amended, each BLA must be accompanied by a user fee.

The FDA adjusts the PDUFA

user fees on an annual basis.

The FDA adjusts

the PDUFA user fees on an annual basis.

Fee waivers or reductions are available in certain circumstances, including a waiver of the application

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Under the goals and policies agreed to by the FDA under PDUFA, the FDA has

months, from the filing date, in which to complete its initial review of an original BLA and respond to the applicant, and six months

10 months, from the filing date, in which to complete its initial review of an original BLA and respond to the applicant, and 6 months

from the filing date of an original BLA designated for priority review.

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pre-approval inspection of the manufacturing facilities for the new product to determine whether they comply with cGMP requirements.

FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements

and adequate to assure consistent production of the product within required specifications.

The FDA also may audit data from clinical

trials to ensure compliance with GCP requirements.

Additionally, the FDA may refer applications for novel products or products which present

difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for

review, evaluation and a recommendation as to whether the application should be approved and under what conditions, if any.

not bound by recommendations of an advisory committee, but it considers such recommendations when making decisions on approval.

likely will reanalyze the clinical trial data, which could result in extensive discussions between the FDA and the applicant during the

review process.

The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP

requirements and adequate to assure consistent production of the product within required specifications.

The FDA also may audit data

from clinical trials to ensure compliance with GCP requirements.

Additionally, the FDA may refer applications for novel products or products

which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other

experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions, if any.

The FDA is not bound by recommendations of an advisory committee, but it considers such recommendations when making decisions on approval.

The FDA likely will reanalyze the clinical trial data, which could result in extensive discussions between the FDA and the applicant

during the review process.

After the FDA evaluates a BLA, it will issue an

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United States for this type of disease or condition will be recovered from sales of the product.

Orphan drug designation for a biologic

must be requested before submitting a BLA.

After the FDA grants orphan drug designation, the identity of the therapeutic agent and its

potential orphan use are disclosed publicly by the FDA.

orphan drug designation does not convey any advantage in or shorten the duration

of the regulatory review and approval process.

Orphan drug designation for a biological

product must be requested before submitting a BLA.

After the FDA grants orphan drug designation, the identity of the therapeutic agent

and its potential orphan use are disclosed publicly by the FDA.

orphan drug designation does not convey any advantage in or shorten the

duration of the regulatory review and approval process.

Orphan drug designation entitles a party to financial

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to patient care, or in instances of drug supply issues.

Competitors, however, may receive approval of either a different product for the

same indication or the same product for a different indication but that could be used off-label in the orphan indication.

exclusivity also could block the approval of one of our products for seven years if a competitor obtains approval before we do for the

same product, as defined by the FDA, for the same indication we are seeking approval, or if our product is determined to be contained

Competitors, however, may receive approval of either a different product for

the same indication or the same product for a different indication but that could be used off-label in the orphan indication.

drug exclusivity also could block the approval of one of our products for seven years if a competitor obtains approval before we do for

the same product, as defined by the FDA, for the same indication we are seeking approval, or if our product is determined to be contained

within the scope of the competitor’s product for the same indication or disease.

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approval if it treats a serious or life-threatening condition and demonstrates an effect on a surrogate endpoint that is reasonably likely

to predict clinical benefit or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, or IMM, that

is reasonably likely to predict an effect on IMM or other clinical benefit.

As a condition of approval, the FDA generally requires that

a sponsor of a drug or biologic receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials.

receiving accelerated approval may be subject to expedited withdrawal procedures if such clinical trials fail to verify the predicted

clinical benefit or if the sponsor fails to conduct such trials in a timely manner.

to predict clinical benefit or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, or IMM,

that is reasonably likely to predict an effect on IMM or other clinical benefit.

As a condition of approval, the FDA generally requires

that a sponsor of a drug or biologic receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials

to demonstrate clinical benefit.

Products receiving accelerated approval may be subject to expedited withdrawal procedures if such clinical

trials fail to verify the predicted clinical benefit or if the sponsor fails to conduct such trials in a timely manner.

Additionally, a drug or biologic may be eligible

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review or approval may not be shortened.

Furthermore, fast track designation, priority review, accelerated approval and breakthrough therapy

designation do not change the standards for approval, but may expedite the development or approval process.

Furthermore, fast track designation, priority review, accelerated approval and breakthrough

therapy designation do not change the standards for approval, but may expedite the development or approval process.

Pediatric Information

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to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen

or new route of administration must submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-Phase 2 meeting or,

if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 study.

The initial PSP must include

an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant

endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of

pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information.

or new route of administration must submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-Phase 2 meeting

or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 study.

The initial PSP must

include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups,

relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral

of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting

The FDA and the sponsor must reach an agreement on the PSP.

A sponsor can submit amendments to an agreed-upon initial PSP at any time

if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or

other clinical development programs.

A sponsor can submit amendments to an agreed-upon initial PSP

at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical

trials and/or other clinical development programs.

Post-marketing Requirements

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safety issue.

Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing.

Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial

FDA regulations require that products be manufactured

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which requires that the biological product be highly similar to the reference product notwithstanding minor differences in clinically

inactive components and that there be no clinically meaningful differences between the product and the reference product in terms of safety,

purity and potency, can be shown through analytical studies, animal studies and a clinical trial or trials.

Interchangeability requires that a biological product

be biosimilar to the reference product and that the product can be expected to produce the same clinical results as the reference product

in any given patient and, for products administered multiple times to an individual, that the product and the reference product may be

alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative

to exclusive use of the reference biological product without such alternation or switch.

inactive components and that there be no clinically meaningful differences between the product and the reference product in terms of

safety, purity and potency, can be shown through analytical studies, animal studies and a clinical trial or trials.

Interchangeability requires that a biological

product be biosimilar to the reference product and that the product can be expected to produce the same clinical results as the reference

product in any given patient and, for products administered multiple times to an individual, that the product and the reference product

may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy

relative to exclusive use of the reference biological product without such alternation or switch.

A reference biological product is granted 12 years

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does not include the date of licensure of (and a new period of exclusivity is not available for) a biological product if the licensure

is for a supplement for the biological product or for a subsequent application by the same sponsor or manufacturer of the biological product

(or licensor, predecessor in interest, or other related entity) for a change (not including a modification to the structure of the biological

product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or

strength, or for a modification to the structure of the biological product that does not result in a change in safety, purity, or potency.

is for a supplement for the biological product or for a subsequent application by the same sponsor or manufacturer of the biological

product (or licensor, predecessor in interest, or other related entity) for a change (not including a modification to the structure of

the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery

device or strength, or for a modification to the structure of the biological product that does not result in a change in safety, purity,

Pediatric exclusivity is another type of regulatory

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require either clearance or approval prior to commercialization.

The level of risk combined with available controls to mitigate risk determines

whether a companion diagnostic device requires Premarket Approval Application approval or is cleared through the 510(k) premarket notification

For a novel therapeutic product for which a companion diagnostic device is essential for the safe and effective use of the product,

the companion diagnostic device should be developed and approved or 510(k)-cleared contemporaneously with the therapeutic.

the companion diagnostic device will be stipulated in the labeling of the therapeutic product.

The level of risk combined with available controls to mitigate risk

determines whether a companion diagnostic device requires Premarket Approval Application approval or is cleared through the 510(k) premarket

notification process.

For a novel therapeutic product for which a companion diagnostic device is essential for the safe and effective

use of the product, the companion diagnostic device should be developed and approved or 510(k)-cleared contemporaneously with the therapeutic.

The use of the companion diagnostic device will be stipulated in the labeling of the therapeutic product.

Government Regulation Outside of the United States

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Whether or not we obtain FDA approval for a product candidate,

we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or

marketing of the product in those countries.

If we fail to comply with applicable foreign regulatory requirements, we may be subject to,

among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions

we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials

or marketing of the product in those countries.

If we fail to comply with applicable foreign regulatory requirements, we may be subject

to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions

and criminal prosecution.

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In the European Union, for example, a clinical trial application, or CTA, must be submitted

for each clinical trial to the relevant national health authority and an independent ethics committee in each country in which the trial

is to be conducted through a single EU portal for harmonized assessment, much like the FDA and an IRB, respectively.

CTAs must be accompanied

by an investigational medicinal product dossier with supporting information prescribed by the Clinical Trials Directive (and corresponding

national laws of the member states) and further detailed in applicable guidance documents.

Once the CTA is approved in accordance with

a country’s requirements, the clinical trial may proceed.

A similar process to the one described for the European Union is required

in Israel for initiation of clinical trials.

The requirements and process governing the conduct of clinical trials vary from country to

In all cases, the clinical trials must be conducted in accordance with GCP and the applicable regulatory requirements and the

ethical principles that have their origin in the Declaration of Helsinki.

for each clinical trial in a centralized manner to the relevant national health authority and an independent ethics committee in each

country in which the trial is to be conducted through a single EU portal for harmonized assessment, much like the FDA and an IRB, respectively.

CTAs must be accompanied by an investigational medicinal product dossier with supporting information prescribed by the Clinical Trials

Regulation (and corresponding national laws of the member states) and further detailed in applicable guidance documents.

is approved in accordance with the European Commission and each country’s requirements, the clinical trial may proceed.

process to the one described for the European Union is required in Israel for initiation of clinical trials.

The requirements and process

governing the conduct of clinical trials vary from country to country.

In all cases, the clinical trials must be conducted in accordance

with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

Approval Process

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is compulsory for certain medicinal products, including for medicinal products produced by certain biotechnological processes, products

designated as orphan medicinal products, advanced therapy medicinal products, or ATMPs, and products with a new active substance and indicated

for the treatment of certain diseases.

For products with a new active substance and indicated for the treatment of other diseases, products

that are highly innovative or for which a centralized process is in the interest of patients, the centralized procedure is optional.

Under the centralized procedure, the Committee

for Medicinal Products for Human Use, or CHMP, the main scientific committee established at the European Medicines Agency, or EMA, is

responsible for conducting the scientific assessment of the future medicinal product.

The CHMP is also responsible for several post-authorization

and maintenance activities, such as the assessment of modifications or extensions to an existing marketing authorization.

timeframe for the evaluation of an MAA is 210 days, excluding clock stops.

The European Commission grants or refuses the marketing authorization,

following a procedure that involves representatives of the member states.

The European Commission’s decision is in accordance with

the CHMP scientific assessment except in very rare cases.

designated as orphan medicinal products, advanced therapy medicinal products, or ATMPs, and products with a new active substance and

indicated for the treatment of certain diseases.

For products with a new active substance and indicated for the treatment of other diseases,

products that are highly innovative or for which a centralized process is in the interest of patients, the centralized procedure is optional.

Under the centralized procedure, the CHMP, the

main scientific committee established at the European Medicines Agency, or EMA, is responsible for conducting the scientific assessment

of the future medicinal product.

The CHMP is also responsible for several post-authorization and maintenance activities, such as the

assessment of modifications or extensions to an existing marketing authorization.

The maximum timeframe for the evaluation of an MAA

is 210 days, excluding clock stops.

The European Commission grants or refuses the marketing authorization, following a procedure that

involves representatives of the member states.

The European Commission’s decision is in accordance with the CHMP scientific assessment

except in very rare cases.

Pursuant to Regulation (EC) 1394/2007, specific

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The hospital exemption, which is in essence a compounded ATMP, has been transposed

in all Member States, sometimes in such a way that the ATMPs under the hospital exemption are competitive alternatives to ATMPs with marketing

authorization.

The broad use of the hospital exemption by national hospitals led the European Commission to discuss with the Member States

a more reasonable application of the hospital exemption that would not undermine the common legal regime for ATMP.

in all Member States, sometimes in such a way that the ATMPs under the hospital exemption are competitive alternatives to ATMPs with

marketing authorization.

The broad use of the hospital exemption by national hospitals led the European Commission to discuss with the

Member States a more reasonable application of the hospital exemption that would not undermine the common legal regime for ATMP.

Marketing authorization is valid for five years

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introduced since the marketing authorization was granted, at least six months before the marketing authorization ceases to be valid.

renewed, the marketing authorization is valid for an unlimited period, unless the European Commission or the national competent authority

decides, on justified grounds relating to pharmacovigilance, to proceed with one additional renewal.

Any authorization which is not followed

by the actual placing of the medicinal product on the European Union market (in case of centralized procedure) or on the market of the

authorizing member state within three years after authorization ceases to be valid (the so-called sunset clause).

Once renewed, the marketing authorization is valid for an unlimited period, unless the European Commission or the national competent

authority decides, on justified grounds relating to pharmacovigilance, to proceed with one additional renewal.

Any authorization which

is not followed by the actual placing of the medicinal product on the European Union market (in case of centralized procedure) or on

the market of the authorizing member state within three years after authorization ceases to be valid (the so-called sunset clause).

Orphan Designation

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For example, in the European Union, Regulation

141/2000 organizes the grant of orphan drug designations to promote the development of products that are intended for the diagnosis, prevention

or treatment of life threatening or chronically debilitating conditions affecting not more than five in 10,000 persons in the European

Economic Area (the European Union, plus Iceland, Liechtenstein and Norway), or EEA, (or where it is unlikely that the development of the

medicine would generate sufficient return to justify the investment) and for which no satisfactory method of diagnosis, prevention or

treatment has been authorized or, if a method exists, the product would be of significant benefit to those affected.

The EMA’s Committee

for Orphan Medicinal Products, or COMP, examines if the orphan criteria are met and gives opinions thereon, and the orphan status is granted

by the European Commission.

The meeting of the criteria for orphan designation is examined again by the COMP at the time of approval of

the medicinal product, which typically occurs several years after the grant of the orphan designation.

If the criteria for orphan designation

are no longer met at that time, the European Commission withdraws the orphan status.

141/2000 organizes the grant of orphan drug designations to promote the development of products that are intended for the diagnosis,

prevention or treatment of life threatening or chronically debilitating conditions affecting not more than 5 in 10,000 persons in the

European Economic Area (the European Union, plus Iceland, Liechtenstein and Norway), or EEA, (or where it is unlikely that the development

of the medicine would generate sufficient return to justify the investment) and for which no satisfactory method of diagnosis, prevention

or treatment has been authorized or, if a method exists, the product would be of significant benefit to those affected.

Committee for Orphan Medicinal Products, or COMP, examines if the orphan criteria are met and gives opinions thereon, and the orphan

status is granted by the European Commission.

The meeting of the criteria for orphan designation is examined again by the COMP at the

time of approval of the medicinal product, which typically occurs several years after the grant of the orphan designation.

If the criteria

for orphan designation are no longer met at that time, the European Commission withdraws the orphan status.

In the European Union, orphan drug designation

entitles the sponsor to financial incentives such as reduction of fees or fee waivers and to ten years of market exclusivity granted following

medicinal product approval.

Market exclusivity precludes the EMA or a national regulatory authority from validating another MAA, and the

European Commission or a national regulatory authority from granting another marketing authorization, for a same or similar medicinal

product and a same therapeutic indication, for that time period.

This 10-year period may be reduced to six years if the orphan drug designation

criteria are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance of market

The orphan exclusivity may be lost vis-à-vis another medicinal product in cases the manufacturer is unable to assure

sufficient quantity of the medicinal product to meet patient needs or if that other product is proved to be clinically superior to the

approved orphan product.

A drug is clinically superior if it is safer, more effective or makes a major contribution to patient care.

drug designation must be requested before submitting a MAA.

Orphan drug designation does not convey any advantage in, or shorten the duration

of, the regulatory review and approval process, and it does not afford any regulatory exclusivity until a marketing authorization is granted.

entitles the sponsor to financial incentives such as reduction of fees or fee waivers and to ten years of market exclusivity granted

following medicinal product approval.

Market exclusivity precludes the EMA or a national regulatory authority from validating another

MAA, and the European Commission or a national regulatory authority from granting another marketing authorization, for a same or similar

medicinal product and a same therapeutic indication, for that time period.

This 10-year period may be reduced to six years if the orphan

drug designation criteria are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance

of market exclusivity.

The orphan exclusivity may be lost vis-à-vis another medicinal product in cases the manufacturer is unable

to assure sufficient quantity of the medicinal product to meet patient needs or if that other product is proved to be clinically superior

to the approved orphan product.

A drug is clinically superior if it is safer, more effective or makes a major contribution to patient

Orphan drug designation must be requested before submitting a MAA.

Orphan drug designation does not convey any advantage in, or

shorten the duration of, the regulatory review and approval process, and it does not afford any regulatory exclusivity until a marketing

authorization is granted.

Expedited Development and Approval

Mechanisms are in place in many jurisdictions that

allow an earlier approval of the drug so that it reaches patients with unmet medical needs earlier.

The European Union, for example, has

instituted several expedited approval mechanisms including two mechanisms that are specific to the centralized procedure:

Mechanisms are in place in many jurisdictions

that allow an earlier approval of the drug so that it reaches patients with unmet medical needs earlier.

The European Union, for example,

has instituted several expedited approval mechanisms including two mechanisms that are specific to the centralized procedure:

the accelerated approval:

the EMA may reduce the maximum timeframe for the evaluation of an MAA from 210 days to 150 days when the future medicinal product is of major interest from the point of view of public health, in particular from the viewpoint of therapeutic innovation.

the EMA may reduce the maximum

timeframe for the evaluation of an MAA from 210 days to 150 days when the future medicinal product is of major interest from the

point of view of public health, in particular from the viewpoint of therapeutic innovation.

the conditional marketing authorization:

as part of its marketing authorization process, the European Commission may grant marketing authorizations on the basis of less complete data than is normally required.

its marketing authorization process, the European Commission may grant marketing authorizations on the basis of less complete data

than is normally required.

A conditional marketing authorization may be granted

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been supplied, all the following requirements are met:

the risk/benefit balance of the medicinal product is positive;

it is likely that the applicant will be in a position to provide the comprehensive clinical data;

the risk/benefit balance of the medicinal product is

it is likely that the applicant will be in a position

to provide the comprehensive clinical data;

unmet medical needs will be addressed;

the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data is still required.

the benefit to public health of the immediate availability

on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data is still required.

The granting of a conditional marketing authorization

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The conditions to which approval is subject will typically require the holder to complete ongoing

trials or to conduct new trials with a view to confirming that the benefit-risk balance is positive and to collect pharmacovigilance data.

trials or to conduct new trials with a view to confirming that the benefit-risk balance is positive and to collect pharmacovigilance

Once the conditions to which the marketing authorization is subject are fulfilled, the conditional marketing authorization is transformed

into a regular marketing authorization.

If, however, the conditions are not fulfilled with the timeframe set by EMA, the conditional marketing

authorization ceases to be renewed.

If, however, the conditions are not fulfilled with the timeframe set by EMA, the conditional

marketing authorization ceases to be renewed.

The EMA has also implemented the so-called “PRIME”

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of the medicinal product is reviewed annually.

As a result, although the MA “under exceptional circumstances” is granted definitively,

the risk-benefit balance of the medicinal product is reviewed annually and the marketing authorization is withdrawn in case the risk-benefit

ratio is no longer favorable.

Mandatory testing in the pediatric population is

required in more and more jurisdictions.

The European Union has enacted a complex and very stringent system that has inspired other jurisdictions,

including the United States and Switzerland.

Any application for approval of (i) a medicinal product containing a new active substance

or (ii) a new therapeutic indication, pharmaceutical form or route of administration of an already authorized medicinal product which

contains an active substance still protected by a supplementary protection certificate, or SPC, or a patent that qualifies for an SPC,

must include pediatric data.

As a result, although the MA “under exceptional circumstances” is granted

definitively, the risk-benefit balance of the medicinal product is reviewed annually and the marketing authorization is withdrawn in

case the risk-benefit ratio is no longer favorable.

Mandatory testing in the pediatric population

is required in more and more jurisdictions.

The European Union has enacted a complex and very stringent system that has inspired other

jurisdictions, including the United States and Switzerland.

Any application for approval of (i) a medicinal product containing a new

active substance or (ii) a new therapeutic indication, pharmaceutical form or route of administration of an already authorized medicinal

product which contains an active substance still protected by a supplementary protection certificate, or SPC, or a patent that qualifies

for an SPC, must include pediatric data.

Otherwise, the application is not validated by the competent regulatory authority.

The submission of pediatric

data is mandatory in those cases, even if the application concerns an adult use.

Submission of pediatric data is not required or fully

required if the EMA granted, respectively, a full or partial waiver to pediatric development.

Moreover, that submission can be postponed

if the EMA grants a deferral in order not to delay the submission of the MAA for the adult population.

The submission

of pediatric data is mandatory in those cases, even if the application concerns an adult use.

Submission of pediatric data is not required

or fully required if the EMA granted, respectively, a full or partial waiver to pediatric development.

Moreover, that submission can

be postponed if the EMA grants a deferral in order not to delay the submission of the MAA for the adult population.

The pediatric data are generated through the implementation

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institutes SPCs.

An SPC is an extension of the term of a patent that compensates for the patent protection lost because of the legal requirements

to conduct safety and efficacy tests and to obtain a marketing authorization before placing a medicinal product on the market.

may be applied for any active substance that is protected by a “basic patent” (a patent chosen by the patent holder, which

can be a product, process or application patent) and has not been placed on the market as a medicinal product before having obtained a

marketing authorization in accordance with European Union pharmaceutical law.

An SPC is an extension of the term of a patent that compensates for the patent protection lost because of the legal

requirements to conduct safety and efficacy tests and to obtain a marketing authorization before placing a medicinal product on the market.

An SPC may be applied for any active substance that is protected by a “basic patent” (a patent chosen by the patent holder,

which can be a product, process or application patent) and has not been placed on the market as a medicinal product before having obtained

a marketing authorization in accordance with European Union pharmaceutical law.

The term of the SPC is maximum five years, and the combined

patent and SPC protection may not exceed fifteen years from the date of the first marketing authorization in the EEA.

SPC rights are restricted

by both the basic patent and the marketing authorization, i.e., the SPC grants the same rights as those conferred by the basic patent

but limited to the active substance covered by the marketing authorization (and any use as medicinal product approved afterwards).

SPC rights are

restricted by both the basic patent and the marketing authorization, i.e., the SPC grants the same rights as those conferred by the basic

patent but limited to the active substance covered by the marketing authorization (and any use as medicinal product approved afterwards).

While SPC are regulated at the European level,

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expected length of the clinical trials and other factors involved in the filing of the relevant MAA.

Furthermore, in the European Union, medicinal products

may benefit from the following regulatory exclusivities:

data exclusivity, market protection, market exclusivity, and pediatric reward.

Furthermore, in the European Union, medicinal

products may benefit from the following regulatory exclusivities:

data exclusivity, market protection, market exclusivity, and pediatric

A medicinal product that contains a new active

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product for submission of generic MAA purposes, and market protection prevents other companies from placing generics on the market.

to the concept of global marketing authorization, any further development of that medicinal product (e.g., new indication, new form, change

to the active substance) by the marketing authorization holder does not trigger any new or additional protection.

The authorization of

any new development is considered as “falling” into the initial marketing authorization with regard to regulatory protection;

to the concept of global marketing authorization, any further development of that medicinal product (e.g., new indication, new form,

change to the active substance) by the marketing authorization holder does not trigger any new or additional protection.

The authorization

of any new development is considered as “falling” into the initial marketing authorization with regard to regulatory protection;

hence, the new development only benefits from the regulatory protection that remains when it is authorized.

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is regulated by each member state.

Market exclusivity is a regulatory protection exclusively

afforded to medicinal products with an orphan status.

Market exclusivity precludes the EMA or a national regulatory authority from validating

another MAA, and the European Commission or a national regulatory authority from granting another marketing authorization, for a same

or similar medicinal product and a same therapeutic indication, for a period of ten years from approval (see above).

Market exclusivity is a regulatory protection

exclusively afforded to medicinal products with an orphan status.

Market exclusivity precludes the EMA or a national regulatory authority

from validating another MAA, and the European Commission or a national regulatory authority from granting another marketing authorization,

for a same or similar medicinal product and a same therapeutic indication, for a period of ten years from approval (see above).

Pediatric reward is another regulatory exclusivity.

Completion of a PIP renders the company eligible for a pediatric reward, which can be six-month extension of the term of the SPC or, in

the cases of orphan medicinal products, two additional years of market exclusivity (see above).

Completion of a PIP renders the company eligible for a pediatric reward, which can be six-month extension of the term of the SPC or,

in the cases of orphan medicinal products, two additional years of market exclusivity (see above).

In case a PIP is completed on a voluntary

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the form of a “pediatric use marketing authorization”, or PUMA.

That special authorization does not fall into the global marketing

authorization and thus benefits from eight years of data exclusivity followed by two or three years of market protection.

That special authorization does not fall into the global

marketing authorization and thus benefits from eight years of data exclusivity followed by two or three years of market protection.

Healthcare Laws and Compliance Requirements

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The laws that may affect our ability to operate include:

the federal Anti-Kickback Statute, which prohibits, among other things, knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation of any good, facility, item or service for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs;

a person or entity does not need to have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it to have committed a violation.

In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act, or FCA, or federal civil money penalties statute;

federal civil and criminal false claims laws and civil monetary penalties laws, such as the FCA, which impose criminal and civil penalties and authorize civil whistleblower or qui tam actions, against individuals or entities for, among other things:

knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent;

making, using or causing to be made or used, a false statement or record material to a false or fraudulent claim or obligation to pay or transmit money or property to the federal government;

or knowingly concealing or knowingly and improperly avoiding or decreasing an obligation to pay money to the federal government;

the civil monetary penalties law, which prohibits, among other things, the offering or giving of remuneration, which includes, without limitation, any transfer of items or services for free or for less than fair market value (with limited exceptions), to a Medicare or Medicaid beneficiary that the person knows or should know is likely to influence the beneficiary’s selection of a particular supplier of items or services reimbursable by a federal or state governmental program;

the Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters;

similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;

the federal transparency requirements under the Affordable Care Act, or ACA, including the provision commonly referred to as the Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program to report annually to the U.S.

Department of Health and Human Services information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified registered nurse anesthetists and certified nurse midwives) and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members;

federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs;

federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers.

the federal Anti-Kickback Statute, which prohibits,

among other things, knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe,

or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, either the referral of

an individual, or the purchase, lease, order or recommendation of any good, facility, item or service for which payment may be made,

in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs;

a person or entity does not

need to have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it to have committed a violation.

In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback

Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act, or FCA, or federal civil money penalties

federal civil and criminal false claims laws and civil

monetary penalties laws, such as the FCA, which impose criminal and civil penalties and authorize civil whistleblower or qui tam

actions, against individuals or entities for, among other things:

knowingly presenting, or causing to be presented, to the federal

government, claims for payment that are false or fraudulent;

making, using or causing to be made or used, a false statement or record

material to a false or fraudulent claim or obligation to pay or transmit money or property to the federal government;

concealing or knowingly and improperly avoiding or decreasing an obligation to pay money to the federal government;

the civil monetary penalties law, which prohibits,

among other things, the offering or giving of remuneration, which includes, without limitation, any transfer of items or services

for free or for less than fair market value (with limited exceptions), to a Medicare or Medicaid beneficiary that the person knows

or should know is likely to influence the beneficiary’s selection of a particular supplier of items or services reimbursable

by a federal or state governmental program;

the Health Insurance Portability and Accountability

Act of 1996, or HIPAA, which created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting

to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations,

or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless

of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a

material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits,

items or services relating to healthcare matters;

similar to the federal Anti-Kickback Statute, a person or entity does not need

to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;

the federal transparency requirements under the Affordable

Care Act, or ACA, including the provision commonly referred to as the Physician Payments Sunshine Act, which requires manufacturers

of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s

Health Insurance Program to report annually to the U.S.

Department of Health and Human Services information related to payments or

other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors),

certain non-physician practitioners (physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants,

certified registered nurse anesthetists and certified nurse midwives) and teaching hospitals, as well as ownership and investment

interests held by the physicians described above and their immediate family members;

federal government price reporting laws, which require

us to calculate and report complex pricing metrics in an accurate and timely manner to government programs;

federal consumer protection and unfair competition

laws, which broadly regulate marketplace activities and activities that potentially harm consumers.

Additionally, we are subject to state and foreign

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of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

the approval and commercialization of any of our product candidates outside the United States will also likely subject us to foreign equivalents

of the healthcare laws mentioned above, among other foreign laws.

the approval and commercialization of any of our product candidates outside the United States will also likely subject us to foreign

equivalents of the healthcare laws mentioned above, among other foreign laws.

If any of the physicians or other healthcare providers

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and the amount of reimbursement for particular medical products.

For example, in March 2010, the ACA was enacted, which, among other things,

increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program;

For example, in March 2010, the ACA was enacted, which, among other

things, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program;

introduced a new methodology

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implanted or injected;

extended the Medicaid Drug Rebate Program to utilization of prescriptions of individuals enrolled in Medicaid managed

imposed mandatory discounts for certain Medicare Part D beneficiaries as a condition for manufacturers’ outpatient drugs

coverage under Medicare Part D;

subjected drug manufacturers to new annual fees based on pharmaceutical companies’ share of sales

to federal healthcare programs;

created a new Patient Centered Outcomes Research Institute to oversee, identify priorities in and conduct

comparative clinical effectiveness research, along with funding for such research;

and established the Center for Medicare & Medicaid

Innovation at the CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.

Since its enactment, there have been a number of

significant changes to the ACA.

extended the Medicaid Drug Rebate Program to utilization of prescriptions of individuals enrolled in Medicaid

managed care plans;

imposed mandatory discounts for certain Medicare Part D beneficiaries as a condition for manufacturers’ outpatient

drugs coverage under Medicare Part D;

subjected drug manufacturers to new annual fees based on pharmaceutical companies’ share

of sales to federal healthcare programs;

created a new Patient Centered Outcomes Research Institute to oversee, identify priorities in

and conduct comparative clinical effectiveness research, along with funding for such research;

and established the Center for Medicare

& Medicaid Innovation at the CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.

Since its enactment, there have been a number

of significant changes to the ACA.

On June 17, 2021, the U.S.

Supreme Court dismissed the most recent judicial challenge to the ACA

without specifically ruling on the constitutionality of the ACA.

Supreme Court dismissed the most recent judicial challenge to the

ACA without specifically ruling on the constitutionality of the ACA.

Prior to the U.S.

Supreme Court’s decision, President Biden issued

an executive order initiating a special enrollment period from February 15, 2021 through August 15, 2021 for purposes of obtaining

health insurance coverage through the ACA marketplace.

The executive order also instructed certain governmental agencies to review and

reconsider their existing policies and rules that limit access to healthcare.

More recently, on March 11, 2021, President Biden signed

the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of

a drug’s average manufacturer price, beginning January 1, 2024.

Supreme Court’s decision, President Biden

issued an executive order initiating a special enrollment period from February 15, 2021 through August 15, 2021 for purposes

of obtaining health insurance coverage through the ACA marketplace.

The executive order also instructed certain governmental agencies

to review and reconsider their existing policies and rules that limit access to healthcare.

More recently, on March 11, 2021, President

Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set

at 100% of a drug’s average manufacturer price, beginning January 1, 2024.

In addition, the Budget Control Act of 2011 and

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for coverage and reimbursement and thus any products that are marketed as cosmetics will not be covered or reimbursed.

In the United States

and markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend, in part,

on the availability of coverage and reimbursement from third-party payors.

Third-party payors include government authorities, managed

care providers, private health insurers and other organizations.

The process for determining whether a payor will provide coverage for

a product may be separate from the process for setting the reimbursement rate that the payor will pay for the product.

Third-party payors

may limit coverage to specific products on an approved list, or formulary, which might not include all of the FDA-approved products for

a particular indication.

In the United

States and markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend,

in part, on the availability of coverage and reimbursement from third-party payors.

Third-party payors include government authorities,

managed care providers, private health insurers and other organizations.

The process for determining whether a payor will provide coverage

for a product may be separate from the process for setting the reimbursement rate that the payor will pay for the product.

payors may limit coverage to specific products on an approved list, or formulary, which might not include all of the FDA-approved products

for a particular indication.

A decision by a third-party payor not to cover our products could reduce physician utilization of our products

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decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved.

Adequate third-party reimbursement

may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

Adequate third-party

reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment

in product development.

In addition, coverage and reimbursement for products

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If third-party payors do not consider a product to be cost-effective compared to other available therapies, they may not cover

the product as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its products

the product as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its

products at a profit.

Outside of the United States, the pricing of pharmaceutical

products is subject to governmental control in many countries.

For example, in the European Union, pricing and reimbursement schemes vary

widely from member state to member state.

Some countries provide that products may be marketed only after a reimbursement price has been

Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular therapy to

currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval.

countries may allow companies to fix their own prices for products, but monitor and control product volumes and issue guidance to physicians

to limit prescriptions.

Efforts to control prices and utilization of pharmaceutical products and medical devices will likely continue

as countries attempt to manage healthcare expenditures.

For example, in the European Union, pricing and reimbursement schemes

vary widely from member state to member state.

Some countries provide that products may be marketed only after a reimbursement price

has been agreed.

Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular

therapy to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval.

Other countries may allow companies to fix their own prices for products, but monitor and control product volumes and issue guidance

to physicians to limit prescriptions.

Efforts to control prices and utilization of pharmaceutical products and medical devices will likely

continue as countries attempt to manage healthcare expenditures.

Data Privacy and Security Laws

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Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict

with each other to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant civil

and/or criminal penalties and restrictions on data processing.

with each other to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant

civil and/or criminal penalties and restrictions on data processing.

Material Agreements

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issued certain ordinary shares which were subsequently converted to 193,406 shares of our Common Stock as part of the Business Combination

In the event of certain mergers and acquisitions we are party to, we are obligated to pay Yeda an amount equivalent to approximately 1%

of the consideration received under such transaction.

as defined below under “Liquidity and Capital Resources” .

In the event of certain mergers and acquisitions we are party

to, we are obligated to pay Yeda an amount equivalent to approximately 1% of the consideration received under such transaction.

Unless terminated earlier by either party, the

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in connection with the Yeda 2015 License Agreement.

consults with Yeda with respect to patent

prosecution and maintenance decisions.

Yeda is primarily responsible for prosecution and maintenance with respect to Licensed Information

(as defined in the license) and we are responsible for prosecution and maintenance with respect to Subsequent Results (as defined in the

consults with Yeda with respect to

patent prosecution and maintenance decisions.

Yeda is primarily responsible for prosecution and maintenance with respect to Licensed

Information (as defined in the license) and we are responsible for prosecution and maintenance with respect to Subsequent Results (as

defined in the license).

and Yeda are both entitled to consultation rights.

BiomX is responsible for costs associated with prosecution and

maintenance of all patents and applications.

BiomX is responsible for costs associated with

prosecution and maintenance of all patents and applications.

is entitled to enforce the patent rights

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license (as amended on January 10, 2019, or the USN License Agreement, with the United States of America, as represented by the Secretary

of the Navy or the USN, pursuant to which APT received an exclusive license throughout the territory encompassing the United States, Canada

and Europe to an invention entitled “Bacteriophage Compositions and Method of Selection of Components Against Specific Bacteria

of the Navy or the USN, pursuant to which APT received an exclusive license throughout the territory encompassing the United States,

Canada and Europe to an invention entitled “Bacteriophage Compositions and Method of Selection of Components Against Specific Bacteria

or the USN Licensed Patent, as well as associated materials, including approximately 350 phage (or collectively with the USN Licensed

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of the term of the USN License Agreement.

For the term of the license, any Licensed Invention or product produced through the use of a

Licensed Invention for use or sale in the United States must be manufactured substantially in the United States.

For the term of the license, any Licensed Invention or product produced through the use of

a Licensed Invention for use or sale in the United States must be manufactured substantially in the United States.

The Company uses the

phage provided in connection with the USN License Agreement as a potential source of phage for the development of its phage treatments.

In connection with the USN License Agreement, APT

paid the USN a license execution royalty of $5,000.

In connection with the USN License Agreement,

APT paid the USN a license execution royalty of $5,000.

We are also required to pay royalties expressed as a percentage in the high single

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laboratory methods, related to the Licensed Invention.

APT agreed to pay minimum annual royalties in the

amount of $5,000 from 2018 to 2020 and $20,000 thereafter.

APT agreed to pay minimum annual royalties in

the amount of $5,000 from 2018 to 2020 and $20,000 thereafter.

APT also agreed to pay (a) a regulatory approval royalty in the low $100,000s

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the Licensed Invention by January 1, 2021, and thereafter until such practical application has been received.

We may terminate the USN License Agreement upon

120 days’ written notice, and the USN may terminate the USN License Agreement if (i) the USN determines we are not executing the

Commercial Development Plan, (ii) the USN determines such termination is necessary to meet requirements for public use specified by U.S.

federal regulations issued after the date of the USN License Agreement and not reasonably satisfied by us, (iii) in the event we willfully

made a material false statement or omitted a material fact in our application for the USN License Agreement or any report required thereby,

or (iv) we commit a substantial material breach of the USN License Agreement that has not been remedied within 30 days of written notice.

may terminate the USN License Agreement upon 120 days’ written notice, and the USN may terminate the USN License Agreement if (i)

the USN determines we are not executing the Commercial Development Plan, and cannot demonstrate progression towards practical application,

(ii) the USN determines such termination is necessary to meet requirements for public use specified by U.S.

federal regulations issued

after the date of the USN License Agreement and not reasonably satisfied by us, (iii) in the event we willfully made a material false

statement or omitted a material fact in our application for the USN License Agreement or any report required thereby, (iv) we commit

a substantial material breach of the USN License Agreement that has not been remedied within 30 days of written notice, (v) we file for

bankruptcy, become subject to bankruptcy proceedings, or assign the agreement without USN approval, or (vi) the agreement automatically

terminates on May 1, 2025, unless a new agreement is executed.

Upon termination, all rights to the Licensed Patents, USN Materials, and

data revert to the USN.

License Agreement with Walter Reed Army Institute

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the WRAIR Materials, or the WRAIR Licensed Products, subject to reductions as described in the WRAIR License Agreement.

In addition, if

we sublicense our rights under the WRAIR License Agreement we are obligated to pay WRAIR additional sublicense royalties expressed as

a percentage in the low teens of the sublicensing receipts we receive from any such sublicense royalties.

In addition, additional royalties

in the low teens may be assessed on any overdue royalty payments.

if we sublicense our rights under the WRAIR License Agreement we are obligated to pay WRAIR additional sublicense royalties expressed

as a percentage in the low teens of the sublicensing receipts we receive from any such sublicense royalties.

In addition, additional

royalties in the low teens may be assessed on any overdue royalty payments.

We are obligated to make written annual progress

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to negotiate a non-exclusive or exclusive license.

The WRAIR License Agreement will expire as to each

WRAIR Material ten years from the date that such WRAIR Material was added to the WRAIR License Agreement unless earlier terminated in

accordance with its terms.

We may terminate the WRAIR License Agreement upon 60 days’ written notice, and WRAIR may terminate if

we are in default and such default has not been remedied within 90 days after written notice of such default.

The WRAIR License Agreement will expire as to

each WRAIR Material ten years from the date that such WRAIR Material was added to the WRAIR License Agreement unless earlier terminated

in accordance with its terms.

We may terminate the WRAIR License Agreement upon 60 days’ written notice, and WRAIR may terminate

if we are in default and such default has not been remedied within 90 days after written notice of such default.

The MTEC Grant Agreement

Industry and academia have entered into a Consortium

Member Agreement to participate in the Medical Technology Enterprise Consortium, or MTEC, a 501(c)(3) biomedical technology consortium

working in partnership with the U.S.

Department of Defense, for the purpose of conducting research, development and testing in cooperation

with the U.S.

Government in an overall effort to improve Service member health and performance in diverse environments.

In 2019, APT entered

into a Base Agreement and Research Project Award, or, collectively, the Research Agreement, with the U.S.

Army Medical Research Acquisition

Activity, or USAMRAA, and the U.S.

Army Medical Research & Development Command, or USAMRDC, to advance personalized phage therapy

from niche to broad use.

Awards under the Research Agreement are intended to lay the groundwork for rapid advancement of personalized

phage therapy to commercialization for the variety of clinical indications and bacterial pathogens representing un-met needs with a focus

on infections with significant military relevance.

The competitive award was granted by USAMRAA and USAMRDC in collaboration with MTEC.

Under the cost reimbursement contract, MTEC reimburses APT for approved incurred costs that are based upon the achievement of certain

milestones to support the development of personalized phage therapy.

For the period between the Acquisition and December 31, 2024, APT

received an aggregate of $3.5 million in grants from MTEC.

As of December 31, 2024, we had 52 full-time

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is www.biomx.com.

The content of our website is not intended to be incorporated by reference into this Annual Report or in any other report

or document we file and any references to these websites are intended to be inactive textual references only.

The content of our website is not intended to be incorporated by reference into this Annual Report or in any other

report or document we file and any references to these websites are intended to be inactive textual references only.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business