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Item 1. Business

2021-03-04 compared with 2020-02-20 · 645 added, 766 removed, 512 unchanged (73% of the section changed)

We are a diversified clinical-stage company

leveraging the microbiome to develop therapeutics designed to treat gastrointestinal (GI) diseases in areas of high unmet need.

Our lead clinical candidates are:

(1) SYN-004 (ribaxamase) which is designed to degrade certain commonly used intravenous (IV)

beta-lactam antibiotics within the gastrointestinal (GI) tract to prevent microbiome damage, Clostridioides difficile infection

(CDI), overgrowth of pathogenic organisms, the emergence of antimicrobial resistance (AMR), and acute graft-versus-host-disease

(aGVHD) in allogeneic hematopoietic cell transplant (HCT) recipients, and (2) SYN-010 which is intended to reduce the impact of

methane-producing organisms in the gut microbiome to treat an underlying cause of irritable bowel syndrome with constipation (IBS-C).

We are also advancing SYN-020, an early-stage oral formulation of the enzyme intestinal alkaline phosphatase (IAP) to treat

both local GI and systemic diseases.

developing therapeutics designed to treat gastrointestinal (GI) diseases in areas of high unmet need.

Our lead clinical development

candidates are:

(1) SYN-004 (ribaxamase) which is designed to degrade certain commonly used intravenous (IV) beta-lactam

antibiotics within the GI tract to prevent microbiome damage, Clostridioides difficile infection (CDI), overgrowth of pathogenic

organisms, the emergence of antimicrobial resistance (AMR), and acute graft-versus-host-disease (aGVHD) in allogeneic hematopoietic

cell transplant (HCT) recipients, and (2) SYN-020, a recombinant oral formulation of the enzyme intestinal alkaline phosphatase

(IAP) produced under cGMP conditions and intended to treat both local GI and systemic diseases.

We plan to explore and evaluate a range

of strategic options, which may include:

in-licensing opportunities;

evaluation of potential acquisitions;

or other potential strategic

transactions.

In the meantime, we remain focused on working with our clinical development partners to advance the planned Phase

1b/2a clinical trial of SYN-004 (ribaxamase) in allogeneic hematopoietic cell transplant (HCT) patients, and advancing the clinical

development program for SYN-020 intestinal alkaline phosphatase (IAP) in multiple potential indications.

Our Product Pipeline

aGVHD acute graft-vs-host disease;

allogeneic hematopoietic cell transplant patients;

AMR antimicrobial resistance;

bIAP bovine intestinal alkaline phosphatase;

CDI Clostridioides difficile

CIC chronic idiopathic constipation;

HCT hematopoietic cell transplant patients;

IBS-C irritable

bowel syndrome with constipation;

VRE vancomycin resistant enterococci.

¹Additional products with preclinical proof-of-concept

include SYN-006 (carbapenemase) being designed to prevent aGVHD and infection by carbapenem resistant enterococci and SYN-007 (ribaxamase)

DR being designed to prevent antibiotic associated diarrhea with oral β-lactam antibiotics.

CDI Clostridioides difficile infection.

SAD single ascending dose

¹Additional products with preclinical

proof-of-concept include SYN-006 (carbapenemase) designed to prevent aGVHD and infection by vancomycin resistant enterococci and

SYN-007 (ribaxamase) DR designed to prevent antibiotic associated diarrhea with oral β-lactam antibiotics.

²Dependent on funding/partnership.

*Based on management’s current beliefs

³Announced option-license agreement

with Massachusetts General Hospital to develop SYN-020 in several potential indications related to inflammation and gut barrier

*Based on management’s current beliefs

and expectations.

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(oral enzyme)

outcomes from End of Phase 2 meeting, including FDA-proposed criteria for Phase 3 clinical efficacy and safety which, if achieved,

may support submission for marketing approval on the basis of a single Phase 3 clinical trial (Q4 2018)

initiation of the Phase 3 clinical program proposed by the FDA for the prevention of CDI only after securing additional potential

funding via a strategic partnership

market/potential partner needs and identified potential additional indications in specialty patient populations such as allogeneic

outcomes from End of Phase 2 meeting, including Food and Drug Administration (FDA)-proposed criteria for Phase 3 clinical efficacy

and safety which, if achieved, may support submission for marketing approval on the basis of a single Phase 3 clinical trial (Q4

Identified potential additional indications in specialty patient populations such as allogeneic

hematopoietic cell transplant (HCT) patients

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safety, tolerability and pharmacokinetics in up to 36 evaluable adult allogeneic HCT recipients (Q3 2019)

Received official meeting minutes from FDA Type-C meeting held on December 2, 2019 to discuss

development in allogeneic HCT recipients who are administered IV beta-lactam antibiotics in response to fever (Q1 2020)

initiation of proposed Phase 1b/2a clinical trial to be conducted by Washington University in adult allogeneic HCT recipients in

Treatment of IBS-C

(oral modified-release

lovastatin lactone)

key elements of Pivotal Phase 2b/3 clinical trial design pursuant to consultations with FDA (Q1 2017)

into agreement with CSMC for an investigator-sponsored Phase 2b clinical study of SYN-010 to evaluate SYN-010 dose response and

inform Phase 3 clinical development (Q3 2018)

enrollment in the Phase 2b investigator-sponsored clinical study of SYN-010 conducted by CSMC (Q1 2019)

a data readout from investigator-sponsored Phase 2b clinical study (1H 2020)

official meeting minutes from FDA Type-C meeting held on December 2, 2019 to discuss development in allogeneic HCT recipients

who are administered IV beta-lactam antibiotics in response to fever (Q1 2020)

Received written notification from

the FDA informing the Company that the FDA determined the Phase 1b/2a clinical program in adult hematopoietic cell transplant

(HCT) recipients may proceed per the submitted clinical program protocol (Q3 2020)

Received approval from the Institutional

Review Board (IRB) at Washington University to commence the Phase 1b/2a clinical trial in allogeneic HCT recipients (Q4 2020)

University has begun screening patients for enrollment of the first of three antibiotic cohorts for the Phase 1b/2a clinical

trial of SYN-004 in adult HCT recipients (Q1 2021).

Preserve gut barrier, treat local GI inflammation, and restore gut microbiome

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requirements (Q2 2019)

IND filing (Q2 2020)

into an agreement with Massachusetts General Hospital (“MGH”) granting the Company an option for an exclusive license

to intellectual property and technology related to the use of IAP to maintain GI and microbiome health, diminish systemic inflammation,

and treat age-related diseases (Q2 2020)

IND application with U.S.

FDA supporting an initial indication for the treatment of radiation enteropathy secondary to pelvic

cancer therapy (Q2 2020)

study-may-proceed letter from U.S.

FDA to conduct a Phase 1 single ascending dose study in healthy volunteers, designed to evaluate

SYN-020 for safety, tolerability, and pharmacokinetic parameters (Q3 2020)

Phase 1 single-ascending-dose (SAD) study is expected to commence during the second quarter of 2021.

A topline data readout

is anticipated during the third quarter of 2021, pandemic conditions permitting.

Prevention of CDI, overgrowth of pathogenic organisms and AMR (Degrade IV carbapenem antibiotics)

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microbiome protection in a pig model of ertapenem administration (Q1 2018)

Reported supporting data demonstrating SYN-006 attenuated emergence of antibiotic resistance in a pig model, including

encoded beta-lactamases and genes conferring resistance to a broad range of antibiotics such as aminoglycosides and macrolides

supporting data demonstrating SYN-006 attenuated emergence of antibiotic resistance in a pig model, including encoded beta-lactamases

and genes conferring resistance to a broad range of antibiotics such as aminoglycosides and macrolides (Q1 2019)

Prevention of CDI, overgrowth of pathogenic organisms and AMR (Degrade oral beta-lactam antibiotics)

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(monoclonal antibody

supportive preclinical data demonstrating that an extended half-life version of hu1B7, a component of SYN-005, provided protection

from pertussis for five weeks in a neonatal non-human primate study (Q4 2017)

Collaboration

with UT Austin

Our Microbiome-Focused Pipeline

Reported supportive preclinical

data demonstrating that an extended half-life version of hu1B7, a component of SYN-005, provided protection from pertussis for

five weeks in a neonatal non-human primate study (Q4 2017)

Our Gastrointestinal (GI) and Microbiome-Focused

Our SYN-004 (ribaxamase) and SYN-020 clinical

programs are focused on the gut microbiome, which is home to billions of microbes and composed of a natural balance of both “good”

beneficial species and potentially “bad” pathogenic species.

When the natural balance or normal function of these microbial

species is disrupted, a person’s health can be compromised.

All of our programs are supported by our growing intellectual

property portfolio.

We are maintaining and building our patent portfolio through:

programs are focused on the gastrointestinal tract (GI) and the gut microbiome, which is home to billions of microbial species

and composed of a natural balance of both “good”

beneficial species and potentially “bad”

pathogenic species.

When the natural balance or normal function of these microbial species is disrupted, a person’s health can be compromised.

All of our programs are supported by our growing intellectual property portfolio.

We are maintaining and building our patent portfolio

filing new patent applications;

prosecuting existing

prosecuting existing applications;

and licensing and acquiring new patents and patent

applications.

and licensing and acquiring new patents and patent applications.

SYN-004 (ribaxamase) — Prevention

SYN-004 (ribaxamase) —

of antibiotic-mediated microbiome damage, C.

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and include the commonly used penicillin and cephalosporin classes of antibiotics.

difficile Infection

difficile is the leading type

of hospital acquired infection and is frequently associated with IV beta-lactam antibiotic treatment.

The CDC identified C.

difficile as an “urgent public health threat,” particularly given its resistance to many drugs used to treat other

CDI is a major unintended risk associated with the prophylactic or therapeutic use of IV antibiotics, which may adversely

alter the natural balance of microflora that normally protect the GI tract, leading to C.

Clostridioides difficile Infection

Clostridioides

difficile (formerly known as Clostridium difficile and often called C.

difficile or CDI) is the leading

type of hospital acquired infection and is frequently associated with IV beta-lactam antibiotic treatment.

The Centers for Disease

Control and Prevention (CDC) identified C.

difficile as an “urgent public health threat,”

particularly given

its resistance to many drugs used to treat other infections.

CDI is a major unintended risk associated with the prophylactic or

therapeutic use of IV antibiotics, which may adversely alter the natural balance of microflora that normally protect the GI tract,

leading to C.

difficile overgrowth and infection.

Other risk factors for CDI include hospitalization, prolonged length of stay (estimated at 7 days), underlying illness, and immune-compromising

conditions including the administration of chemotherapy and advanced age.

According to a paper published in BMC Infectious Diseases

(Desai K et al.

Other risk factors for CDI include hospitalization, prolonged length of

stay (estimated at 7 days), underlying illness, and immune-compromising conditions including the administration of chemotherapy

and advanced age.

According to a paper published in BMC Infectious Diseases (Desai K et al.

BMC Infect Dis.

303) the economic cost of CDI was approximately $5.4 billion in 2016 ($4.7 billion in

healthcare settings;

$725 million in the community) in the U.S., mostly due to hospitalizations.

economic cost of CDI was approximately $5.4 billion in 2016 ($4.7 billion in healthcare settings;

$725 million in the community)

in the U.S., mostly due to hospitalizations.

Limitations of Current Treatments and

Market Opportunit y

Market Opportunity

CDI is a widespread and often drug resistant

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resulting in 10 million deaths worldwide by 2050 and may cost as much as $100 trillion in worldwide economic output.

According to a paper published in BMC

Infectious Diseases (Desai K (2016) Epidemiological and economic burden of Clostridium difficile in the United States:

estimates from a modeling approach.

According to a paper published in BMC Infectious

Diseases (Desai K (2016) Epidemiological and economic burden of Clostridium difficile in the United States:

estimates from

a modeling approach.

BMC Infect Dis 16:

303), it is estimated that approximately 606,000 patients are infected

difficile annually in the U.S., and it has been reported that approximately 44,500 deaths are attributable to

CDI-associated complications each year.

According to IMS Health Incorporated*, in 2016, the potential addressable market for

SYN-004 (ribaxamase) included approximately 227 million doses of intravenous Penicillin and Cephalosporin antibiotics which

were administered in the United States and which may contribute to the onset of CDI.

Additional data derived from IMS Health

Incorporated states that in 2016, the worldwide market for SYN-004 (ribaxamase)-addressable intravenous beta-lactam

antibiotics was approximately 7.5 billion doses, which may represent a multi-billion-dollar market opportunity for

If approved, SYN-004 (ribaxamase) would be the first therapeutic intervention indicated to prevent the onset of

antibiotic-mediated primary CDI.

303), it is estimated that approximately 606,000 patients are infected with C.

annually in the U.S., and it has been reported that approximately 44,500 deaths are attributable to CDI-associated complications

According to IMS Health Incorporated*, in 2016, the potential addressable market for SYN-004 (ribaxamase) included approximately

227 million doses of intravenous Penicillin and Cephalosporin antibiotics which were administered in the United States and which

may contribute to the onset of CDI.

Additional data derived from IMS Health Incorporated states that in 2016, the worldwide market

for SYN-004 (ribaxamase)-addressable intravenous beta-lactam antibiotics was approximately 7.5 billion doses, which may represent

a multi-billion-dollar market opportunity for us.

If approved, SYN-004 (ribaxamase) would be the first therapeutic intervention

indicated to prevent the onset of antibiotic-mediated primary CDI.

Phase 1a and 1b Clinical Trial Pharmacokinetic

In March 2015, we reported supportive pharmacokinetic

data from a Phase 1a clinical trial, which suggested that SYN-004 (ribaxamase) should have no effect on the IV antibiotic in the

bloodstream, allowing the antibiotic to fight the primary infection.

In February 2015, we reported supportive topline results from

a subsequent Phase 1b clinical trial of escalating doses of oral SYN-004 (ribaxamase), with no safety or tolerability issues reported

at dose levels and dosing regimens that were equivalent to or exceeded those expected to be studied in subsequent clinical trials.

The Phase 1a (40 participants) and 1b (24 participants) clinical trials of SYN-004 (ribaxamase) were initiated in December 2014.

In March 2015, we reported supportive

pharmacokinetic data from a Phase 1a clinical trial, which suggested that SYN-004 (ribaxamase) should have no effect on the IV

antibiotic in the bloodstream, allowing the antibiotic to fight the primary infection.

In February 2015, we reported supportive

topline results from a subsequent Phase 1b clinical trial of escalating doses of oral SYN-004 (ribaxamase), with no safety or tolerability

issues reported at dose levels and dosing regimens that were equivalent to or exceeded those expected to be studied in subsequent

clinical trials.

The Phase 1a (40 participants) and 1b (24 participants) clinical trials of SYN-004 (ribaxamase) were initiated

in December 2014.

Two Phase 2a Clinical Trials:

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tolerated by all participants in this clinical trial.

Phase 2b Proof of Concept Clinical Trial Design & Results

In September 2015, we initiated a multicenter,

randomized, placebo-controlled Phase 2b proof-of-concept clinical study in 412 patients (206 per group).

Phase 2b Proof of Concept Clinical Trial Design &

In September 2015, we initiated a

multicenter, randomized, placebo-controlled Phase 2b proof-of-concept clinical study in 412 patients (206 per group).

On January 5, 2017, we announced positive

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IMS expressly reserves all rights, including rights of copying, distribution, and republication.

On October 6, 2016 we were awarded a government

contract in the amount of $521,014 by the Centers for Disease Control and Prevention’s (CDC) Broad Agency Announcement (BAA)

2016-N-17812 to examine changes in the gut resistome of patients in our Phase 2b clinical study.

Data generated under this contract

are consistent with SYN-004’s (ribaxamase) mode of action of preserving the normal gut flora by degrading ceftriaxone in

the upper GI tract of study participants treated with SYN-004 (ribaxamase).

The data further demonstrated that SYN-004 (ribaxamase)

significantly reduced the loss of microbial diversity, reduced overgrowth of opportunistically pathogenic species, and reduced

the emergence of antimicrobial resistance (AMR) genes (such as VRE) caused by ceftriaxone treatment in SYN-004 (ribaxamase) treated

patients compared to placebo.

On October 6, 2016 we were awarded

a government contract in the amount of $521,014 by the CDC’s Broad Agency Announcement (BAA) 2016-N-17812 to examine changes

in the gut resistome of patients in our Phase 2b clinical study.

Data generated under this contract are consistent with SYN-004’s

(ribaxamase) mode of action of preserving the normal gut flora by degrading ceftriaxone in the upper GI tract of study participants

treated with SYN-004 (ribaxamase).

The data further demonstrated that SYN-004 (ribaxamase) significantly reduced the loss of microbial

diversity, reduced overgrowth of opportunistically pathogenic species, and reduced the emergence of antimicrobial resistance (AMR)

genes (such as VRE) caused by ceftriaxone treatment in SYN-004 (ribaxamase) treated patients compared to placebo.

Future Planning and Potential Regulatory

Strategy for Prevention of Primary CDI

On November 21, 2018, we announced results

from our End-of-Phase 2 meeting with the FDA during which key elements of a Phase 3 clinical program were confirmed.

the meeting, the FDA proposed criteria for Phase 3 clinical efficacy and safety which, if achieved, may support submission for

On November 21, 2018, we announced

results from our End-of-Phase 2 meeting with the FDA during which key elements of a Phase 3 clinical program were confirmed.

to the meeting, the FDA proposed criteria for Phase 3 clinical efficacy and safety which, if achieved, may support submission for

marketing approval of SYN-004 (ribaxamase) on the basis of a single Phase 3 clinical trial.

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endpoint is high and the clinical development may be less costly.

We believe allogenic hematopoietic cell

We believe allogeneic hematopoietic cell

transplant (HCT) recipients, who have a very high risk of CDI, VRE colonization and potentially fatal bacteremia, and acute-graft-vs-host

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spectrum of antibiotics used during HCT.

CDI occurs in up to 31% of HCT

patients and is associated with GVHD and increased mortality.

aGVHD occurs in 40-60% of allogeneic HCT recipients and is

recognized as a primary contributor to morbidity and mortality in this patient population.

First-line treatments for aGVHD

fail in more than 50% of patients and 2-year survival in patients with steroid refractory aGVHD is only 20%.

study found allogeneic HCT recipients who developed aGVHD had 3-times higher in-hospital mortality and almost 2-fold

higher median hospital costs than patients who did not develop aGVHD.

It has been reported that in-patient costs for

allogeneic HCT in the USA range from $180,000-$300,000 depending on the disease severity.

In 2014, all-cause costs for

allogeneic HCT in the USA were greater than $600,000 per patient (up to 12 months post-transplant).

VRE infection is a

persistent problem in HCT patients and VRE colonization after HCT has been associated with decreased patient survival.

CDI occurs in up to 31% of HCT patients

and is associated with GVHD and increased mortality.

aGVHD occurs in 30-60% of allogeneic HCT recipients and is recognized as a

primary contributor to morbidity and mortality in this patient population.

In 2018, there were approximately 9,000 reported allogeneic

HCT procedures in the USA, an estimated 19,800 procedures in Europe, 9,600 in China, and 3,500 in Japan.

First-line treatments

for aGVHD fail in more than 50% of patients and 2-year survival in patients with steroid refractory aGVHD is only 20%.

study found allogeneic HCT recipients who developed aGVHD had 3-times higher in-hospital mortality and almost 2-fold higher

median hospital costs than patients who did not develop aGVHD.

It has been reported that in-patient costs for allogeneic HCT in

the USA range from $180,000-$300,000 depending on the disease severity.

In 2014, all-cause costs for allogeneic HCT in the USA

were greater than $600,000 per patient (up to 12 months post-transplant).

VRE infection is a persistent problem in HCT patients

and VRE colonization after HCT has been associated with decreased patient survival.

Phase 1b/2a Clinical Study in Allogeneic

HCT Recipients

In August 2019, we entered into a Clinical

Trial Agreement (CTA) with the Washington University School of Medicine (Washington University) to conduct a Phase 1b/2a clinical

trial of SYN-004 (ribaxamase).

Under the terms of this agreement, we will serve as the sponsor of the study and supply SYN-004

(ribaxamase).

Dubberke, Professor of Medicine and Clinical Director, Transplant Infectious Diseases at Washington University

and a member of the SYN-004 (ribaxamase) steering committee will serve as the principal investigator of the clinical trial in collaboration

with his Washington University colleague Dr.

Schroeder, Associate Professor of Medicine, Division of Oncology, Bone Marrow

Transplantation and Leukemia.

On January 7, 2020, we announced the receipt

of official meeting minutes from the FDA following a Type-C meeting held on December 2, 2019 at our request to discuss the development

of SYN-004 (ribaxamase) for treatment of allogeneic HCT recipients who are administered IV beta-lactam antibiotics in response

Based on the final meeting minutes, the Phase 1b/2a clinical trial will comprise a single center, randomized, double-blinded,

placebo-controlled clinical trial of oral SYN-004 (ribaxamase) in up to 36 evaluable adult allogeneic HCT recipients.

of this study is to evaluate the safety, tolerability and potential absorption into the systemic circulation (if any) of 150 mg

oral SYN-004 (ribaxamase) administered to allogeneic HCT recipients four times per day who receive an IV beta-lactam antibiotic

to treat fever.

Study participants will be enrolled into three sequential cohorts administered a different study-assigned IV beta-lactam

In August 2019, we entered into a

Clinical Trial Agreement (CTA) with the Washington University School of Medicine (Washington University) to conduct a Phase 1b/2a

clinical trial of SYN-004 (ribaxamase).

Under the terms of this agreement, we will serve as the sponsor of the study and supply

SYN-004 (ribaxamase).

Dubberke, Professor of Medicine and Clinical Director, Transplant Infectious Diseases at

Washington University and a member of the SYN-004 (ribaxamase) steering committee will serve as the principal investigator of the

clinical trial in collaboration with his Washington University colleague Dr.

Schroeder, Associate Professor of Medicine,

Division of Oncology, Bone Marrow Transplantation and Leukemia.

On January 7, 2020, we announced the

receipt of official meeting minutes from the FDA following a Type-C meeting held on December 2, 2019 at our request to discuss

the development of SYN-004 (ribaxamase) for treatment of allogeneic HCT recipients who are administered IV beta-lactam antibiotics

in response to fever.

Based on the final meeting minutes, the Phase 1b/2a clinical trial will comprise a single center, randomized,

double-blinded, placebo-controlled clinical trial of oral SYN-004 (ribaxamase) in up to 36 evaluable adult allogeneic HCT recipients.

The goal of this study is to evaluate the safety, tolerability and potential absorption into the systemic circulation (if any)

of 150 mg oral SYN-004 (ribaxamase) administered to allogeneic HCT recipients four times per day who receive an IV beta-lactam

antibiotic to treat fever.

Study participants will be enrolled into three sequential cohorts administered a different study-assigned

IV beta-lactam antibiotic.

Eight participants in each cohort will receive SYN-004 (ribaxamase) and four will receive placebo.

Safety and pharmacokinetic data for each

cohort will be reviewed by an independent Data and Safety Monitoring Committee, which will make a recommendation on whether to

proceed to the next IV beta-lactam antibiotic.

The clinical trial will also evaluate potential protective effects of SYN-004 (ribaxamase)

on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient outcomes of SYN-004

(ribaxamase) in allogeneic HCT recipients.

Enrollment is expected to begin during the second quarter of 2020 contingent upon approval

of the clinical study protocol by the Washington University School of Medicine’s Institutional Review Board (IRB) and the

SYN-010 — Treatment

and pharmacokinetic data for each cohort will be reviewed by an independent Data and Safety Monitoring Committee, which will make

a recommendation on whether to proceed to the next IV beta-lactam antibiotic.

The study will also evaluate potential protective

effects of SYN-004 on the gut microbiome as well as generate preliminary information on potential therapeutic benefits and patient

outcomes of SYN-004 in allogeneic HCT recipients.

On July 30, 2020, we received written

notification from the FDA informing us that they determined the Phase 1b/2a clinical program in adult allogeneic HCT recipients

may proceed per the submitted clinical program protocol.

On December 22, 2020, we announced we received approval from the

Institutional Review Board (IRB) at Washington University to commence the Phase 1b/2a clinical trial of SYN-004.

During the first

quarter of 2021, Washington University began screening patients for enrollment of the first of three antibiotic cohorts in the

Phase 1b/2a clinical trial of SYN-004 in allogeneic HCT recipients.

If enrollment proceeds as planned, we may be positioned to

announce as many as three interim data readouts during the next 12-18 months with the first one anticipated from the first antibiotic

cohort towards the end of 2021, pandemic conditions permitting.

Due to the unique challenges posed by the

global COVID-19 pandemic, Washington University continues to evaluate non-essential activities which may have a direct impact on

planned and ongoing clinical trials.

Continuation of the Phase 1b/2a clinical trial including, but not limited to, the enrollment

of new patients remains largely at the discretion of Washington University and is contingent upon their ability to conduct this

clinical program free from the impact of COVID-19.

We remain in close contact with Washington University and are actively monitoring

the crisis caused by the spread of COVID-19 and its impact to the clinical development plans for our SYN-004 (ribaxamase) program.

SYN-020 —

Oral Intestinal

Alkaline Phosphatase (IAP)

SYN-020 is a quality-controlled, recombinant

version of bovine Intestinal Alkaline Phosphatase (IAP) produced under cGMP conditions and formulated for oral delivery.

The published

literature indicates that IAP functions to diminish GI inflammation, tighten the gut barrier to diminish “leaky gut,”

promote a healthy microbiome, and diminish GI and systemic inflammation.

Despite its broad therapeutic potential, a key hurdle

to commercialization has been the high cost of IAP manufacture which is commercially available for as much as $10,000 per gram.

We believe we have developed technologies to traverse this hurdle and now have the ability to produce more than 3 grams per liter

of SYN-020 for roughly a few hundred dollars per gram at commercial scale.

Based on the known mechanisms as well as our own supporting

animal model data, we intended to initially develop SYN-020 to mitigate the intestinal damage caused by radiation therapy that

is routinely used to treat pelvic cancers, including the treatment and prevention of radiation enteropathy secondary to cancer

And, while we believe SYN-020 may play a pivotal role in addressing acute and long-term complications associated with

radiation exposure to the GI tract, we have begun planning to develop SYN-020 in indications that may offer a more accelerated

or streamlined pathway to registration while also addressing significant unmet medical needs.

Such indications include, celiac

disease, non-alcoholic fatty liver disease (“NAFLD”), and indications supported by our collaboration with Massachusetts

General Hospital (“MGH”).

Across the six major markets, the total prevalent cases of celiac disease are expected to

increase from 5.8 million cases in 2013 to an expected 8.1 million cases in 2023, representing an annual growth rate of approximately

During the same period, prevalent cases in the U.S.

are expected to increase from 2.8 million in 2013 to an expected 4.3 million

in 2023, representing a significant market opportunity.

On June 30, 2020, we submitted an

IND application to the FDA in support of an initial indication for the treatment of radiation enteropathy secondary to pelvic cancer

On July 30, 2020, we announced that we received a study-may-proceed letter from the FDA to conduct a Phase 1 single-ascending-dose

(“SAD”) study in healthy volunteers designed to evaluate SYN-020 for safety, tolerability and pharmacokinetic parameters.

Enrollment is expected to commence during the second quarter of 2021 and a topline data readout is anticipated during the third

quarter of 2021.

Planning for a second Phase 1 study evaluating multiple-ascending doses (“MAD”) of SYN-020 is also

underway and anticipated to commence during the third quarter of 2021.

A topline data readout of the Phase 1 MAD clinical study

is anticipated during the first quarter of 2022, pandemic conditions permitting.

Following the completion of Phase 1 safety studies, we may consider conducting a placebo-controlled Phase 1b/2a challenge study in as many as 40 celiac patients

who present with predominantly GI symptoms followed by a Phase 2b proof-of-concept clinical trial in a similar patient population.

We may also seek to initiate clinical trials of SYN-020 evaluating its potential therapeutic benefit in NAFLD patients.

During the second quarter of 2020, we announced

that we entered into an agreement with Massachusetts General Hospital granting us an option for an exclusive license to intellectual

property and technology related to the use of IAP to maintain GI and microbiome health, diminish systemic inflammation, and treat

age-related diseases.

Research published by a team of investigators led by Richard Hodin, MD, Chief of the Massachusetts General

Hospital Division of General and Gastrointestinal Surgery and Professor of Surgery, Harvard Medical School, evaluated long-term

oral supplementation of IAP, including SYN-020, in mice.

Hodin’s research demonstrated that IAP administration,

starting at 10 months of age, slowed the microbiome changes, gut-barrier dysfunction, and gastrointestinal and systemic inflammation

that normally accompany aging.

Additionally, the IAP administration resulted in improved metabolic profiles in the aged mice, diminished

frailty, and extended lifespan.

Under the terms of the agreement, we are granted exclusive rights to negotiate a worldwide license

with MGH to commercially develop SYN-020 to treat and prevent metabolic and inflammatory diseases associated with aging.

we plan to use this license in the advancement of an expanded clinical development program for SYN-020.

SYN-010 —

of Irritable Bowel Syndrome with Constipation (IBS-C)

SYN-010 is our proprietary, modified-release

formulation of lovastatin lactone that is intended to reduce methane production by certain microorganisms ( Methanobrevibacter

smithii ) in the gut while minimizing disruption to the microbiome.

Methane produced by M.

smithii is an underlying cause

of pain, bloating and constipation associated with IBS-C, and published reports have associated higher intestinal methane production

with increased constipation severity in IBS-C patients.

SYN-010 is intended to act primarily in the intestinal lumen while avoiding

systemic absorption, thereby targeting a major cause of IBS-C while minimizing potential unnecessary systemic effects.

is anticipated to be a chronic, daily therapy and is intended to normalize bowel movements rather than simply reacting to the patient’s

We believe SYN-010 may reduce the impact

of methane producing organisms on IBS-C.

Irritable Bowel Syndrome

IBS is a functional GI disorder

characterized by gas, abdominal pain, bloating and diarrhea or constipation, or alternating episodes of both.

affects both men and women;

however, two-thirds of diagnosed sufferers are women.

The onset of IBS can begin anytime from

adolescence to adulthood.

Four bowel patterns may be seen with IBS including:

IBS-C (constipation predominant), IBS-D

(diarrhea predominant), IBS-M (mixed diarrhea and constipation) and IBS-U (unsubtyped).

According to GlobalData’s IBS

— Global Drug Forecast and Market Analysis to 2023 (December 2014 ), the prevalence of IBS in adults in the

United States, Europe and Japan was expected to be 41.1 million in 2016, and it has been reported that up to 20 percent of

all IBS patients have IBS-C.

Extensive studies conducted by Dr.

Pimentel and collaborators have shown that overproduction of

methane gas is directly associated with bloating, pain and constipation in IBS-C patients.

Investigators at Cedar Sinai

Medical Center (CSMC) have discovered that inhibiting intestinal methane production may reverse constipation associated with

IBS-C, and may be beneficial in treating other major diseases such as obesity, insulin resistance and type 2 diabetes.

Limitations of Current Treatments and

Market Opportunity

Currently, the FDA approved therapies for

the treatment of IBS-C include prescription and over-the-counter laxatives, which provide patients with temporary symptomatic relief

and often cause diarrhea, but are not designed to and do not treat the underlying cause of pain, bloating and constipation associated

Additionally, these same therapies may come with undesirable safety side-effect profiles, the most common of which

As a result, these therapies have struggled to find adoption in several key markets, including Europe.

this presents an important opportunity for SYN-010.

According to IMS Health Analytics, U.S.

sales in 2016 for IBS-C and Chronic

Idiopathic Constipation (CIC) therapeutics as well as OTC laxatives/products were approximately $2.5 billion.

Overview of our two Phase 2 Clinical

In 2015 and 2016, we reported proof-of-concept

data from our two SYN-010 Phase 2 clinical trials.

The first trial was a randomized, double-blind, placebo-controlled, 4-week

study comparing single daily oral doses of SYN-010 21 mg and 42 mg to placebo (Study 1).

Patients who completed Study 1 were eligible

to participate in a follow-on open-label extension study where all patients received single daily doses of SYN-010 42 mg for an

additional 8 weeks (Study 2).

The two Phase 2 SYN-010 clinical trials evaluated the change from baseline (Day 1 of Study 1) in

breath methane, stool frequency and abdominal pain and bloating at the end of weeks 1, 4, 8 and 12 (Study 2 – Day 84) in

patients diagnosed with IBS-C and with breath methane levels greater than 10 parts per million (ppm) at screening.

First Phase 2 Clinical Trial (Study

1) Results (4 Week Placebo-Controlled Acute Study)

In December 2015, we reported topline results

from our first Phase 2 (Study 1) placebo-controlled, randomized clinical trial of SYN-010, including lowered breath methane and

improved stool frequency in patients with IBS-C.

Study 1 was initiated in June 2015 and enrolled 63 patients who were randomized

using a 1:1:1 ratio to one of three groups, including two different SYN-010 dose groups (21 mg and 42 mg) and a placebo group.

Patients received single oral doses of SYN-010 or a placebo each day for 28 days.

The primary objective of Study 1 was to evaluate

the change from baseline in the area under the curve (AUC) of breath methane, as determined by a lactulose breath test, in methane-positive

patients with IBS-C after seven days of treatment with one of two dose levels of SYN-010 as compared with a placebo.

secondary endpoints included improvement in the number of complete spontaneous bowel movements (CSBM) per week, and improvement

in abdominal pain and bloating per standard scales required per FDA guidance.

There were no serious adverse events observed.

In the first Phase 2 clinical trial of

SYN-010, plasma trough levels of lovastatin species were low and variable, such that ≥50% of patients had undetectable plasma

levels of each lovastatin analyte at days 7 and 28.

In the few patients with detectable trough levels at day 28, concentrations

of both lovastatin lactone and lovastatin beta-hydroxyacid were significantly lower than those reported in published studies of

commercial lovastatin formulations.

Second Phase 2 Clinical Trial (Study

2) Results (8 Week Open-Label Extension Study)

In January 2016, we reported topline data

from our second Phase 2 clinical trial (Study 2) of SYN-010, which was initiated in October 2015.

As patients completed Study 1,

they were eligible to immediately rollover into the second Phase 2 clinical trial (multi-center, open-label) of SYN-010 (Study

2) that evaluated the sustainability of the effect of one dose strength of SYN-010 (42 mg) on breath methane production in 54 breath

methane-positive patients with IBS-C, as well as key clinical outcomes, including frequency of CSBM, abdominal pain and bloating.

Patients in Study 2 received a

minimum of 8 weeks of treatment with SYN-010 42 mg.

Study 2 met its primary endpoint as patients who completed Study 2

demonstrated a statistically significant decrease in methane production (p=0.002) from the beginning of Study 1 (Baseline,

Day 1, prior to any drug administration in the randomized study) to the end of Study 2 (12 weeks, Day 84).

Data from Study 2

also showed improvements in secondary efficacy endpoints, including:

(1) a statistically significant reduction in the mean

IBS Symptom Severity Score (IBS-SSS;

p<0.0001), which includes abdominal pain, bloating, stool frequency and quality of

life scores, for all patients from Study 1 baseline to the end of Study 2, and (2) an increase in the percentage of patients

identified as Monthly Responders, an FDA-defined composite measure incorporating improvements in CSBMs and abdominal pain.

Daily doses of SYN-010 were well-tolerated by IBS-C patients over the combined 12 weeks of the Phase 2 clinical trials (Study

1 & Study 2) (at least 8 weeks of SYN-010 42 mg).

No serious adverse events were observed and there were no incidences of

drug-related diarrhea.

Additional Outcomes from Phase 2 Clinical

Trials (Study 1 & Study 2)

We reported additional clinical data at

DDW 2016 from the 57 patients who completed Study 1 and the 54 patients who completed Study 2 demonstrating clinically meaningful

improvements in several measurable endpoints.

The data demonstrated that the 42 mg dose strength of SYN-010 had a similar overall

drug response rate to comparable FDA approved and clinical stage therapies for the treatment of IBS-C with a significantly lower

rate of diarrhea in study participants.

Data from Study 1 also demonstrated that three times as many patients in the placebo group

required rescue medication (laxative) compared to either the 21 mg or 42 mg dose strength of SYN-010.

Patients who participated

in both Study 1 and Study 2 and who were administered the 42 mg dose strength of SYN-010 for at least eight weeks demonstrated

a decrease in breath methane AUC and an increase in complete spontaneous bowel movements (CSBM) (inverse correlation, p=0.0259).

A similar inverse correlation (p=0.0028) was observed between breath methane AUC and spontaneous bowel movements (SBM).

Clear improvements

in abdominal pain, bloating and quality of life measures (IBS-SSS) in participants who were administered SYN-010 were observed

compared to placebo.

Clinical Pharmacokinetic Study

In May 2016, we reported results from a

separate completed randomized, open-label clinical study of healthy volunteers which evaluated the pharmacokinetic (PK) profile

of the active ingredient of SYN-010.

The PK data in healthy volunteers supported the modified-release profile of SYN-010, which

is designed to avoid drug release in the stomach and deliver the antimethanogenic drug form, lovastatin lactone, into the lower

small intestine and colon while reducing systemic exposure to the cholesterol-lowering lovastatin beta-hydroxyacid metabolite.

Lovastatin lactone concentrations in stool samples from these healthy volunteers were equivalent to concentrations that caused

90% inhibition of methane production by stool samples from IBS-C patients in vitro.

Consistent with the Phase 2a studies in IBS-C

patients, data reported from this study demonstrated that the administration of SYN-010 21 mg and 42 mg did not result in adverse

changes to the lipid profiles of study participants.

End of Phase 2 Meeting with FDA

On July 20, 2016, we participated in an

End of Phase 2 meeting with the FDA.

On January 18, 2017, and in accordance with guidance from the FDA, we confirmed the design

of a Phase 2b/3 adaptive clinical study which could be considered our first pivotal trial intended to further evaluate the efficacy,

safety and dose-response of SYN-010.

Consistent with FDA written guidance, the primary objective for this study is to determine

the efficacy of SYN-010, measured as an improvement from baseline in the percentage of overall weekly responders during the 12-week

treatment period 1 for SYN-010 21 mg and 42 mg daily doses compared to placebo.

Secondary efficacy endpoints for both

dose strengths of SYN-010 will measure changes from baseline in abdominal pain, bloating, bowel movement frequency and stool consistency.

Exploratory outcomes include adequate relief and quality of life measures using the well-validated EQ-5D-5L and PAC-SYM patient

questionnaires.

We expect the clinical development costs to complete the Phase 2b/3 clinical trial, as designed, to be in excess

of $80 million.

At this time, we are seeking opportunities to reduce the anticipated clinical costs of potential future registration

studies and anticipate initiating such clinical trials only after securing additional potential financing via a strategic partnership

1 An overall 12-week responder

is defined as a subject with a weekly response in at least 50% of the weeks of treatment (6 of 12 weeks).

Weekly Responder is defined

as a patient who experiences a decrease in weekly average score for worst abdominal pain in the past 24 hours of at least 30% compared

with Study 1 Baseline and a stool frequency increase of 1 or more CSBM per week compared with Study 1 Baseline.

On December 5, 2013, through our majority

owned subsidiary, SYN Biomics, we entered into a worldwide exclusive license agreement (the “CSMC License Agreement”)

for the right to develop, manufacture, use, and sell products, including SYN-010, for the human and veterinary therapeutic and

prophylactic treatments for acute and chronic diseases.

SYN-010 is a modified-release formulation of lovastatin lactone that was

intended to reduce methane production by certain microorganisms ( Methanobrevibacter smithii ) in the gut while minimizing

disruption to the microbiome.

Investigator-Sponsored Phase 2b clinical study

On September 5, 2018, we entered into an

agreement with CSMC for an investigator-sponsored Phase 2b clinical study of SYN-010 to be co-funded by us and CSMC in order to

further evaluate the efficacy and safety of SYN-010.

The Phase 2b study is being conducted out

of the Medically Associated Science and Technology (MAST) Program at CSMC and is a 12-week, placebo-controlled, double-blind, randomized

clinical trial to evaluate two dose strengths of oral SYN-010 21 mg and 42 mg in as many as 150 patients diagnosed with IBS-C using

a breath methane screening level as a criteria for patient enrollment.

The primary objective for the study

is to determine the efficacy of SYN-010, measured as an improvement from baseline in the weekly average number of complete

spontaneous bowel movements (CSBMs) during the 12-week treatment period for SYN-010 21 mg and 42 mg daily doses relative to

Secondary efficacy endpoints for both dose strengths of SYN-010 will measure changes from baseline in abdominal

pain, bloating and stool frequency as well as the use of rescue medication relative to placebo.

Exploratory outcomes include

Adequate Relief and quality of life measures using the well-validated EQ-5D-5L and PAC-SYM patient questionnaires.

On September 5, 2018, we entered into

an agreement with CSMC for an investigator-sponsored Phase 2b clinical study of SYN-010 to be co-funded by us and CSMC in order

to further evaluate the efficacy and safety of SYN-010.

The Phase 2b study was being conducted

out of the Medically Associated Science and Technology (MAST) Program at CSMC and was a 12-week, placebo-controlled, double-blind,

randomized clinical trial to evaluate two dose strengths of oral SYN-010 21 mg and 42 mg in as many as 150 patients diagnosed with

IBS-C using a breath methane screening level as a criteria for patient enrollment.

The primary objective for the study was

to determine the efficacy of SYN-010, measured as an improvement from baseline in the weekly average number of complete spontaneous

bowel movements (CSBMs) during the 12-week treatment period for SYN-010 21 mg and 42 mg daily doses relative to placebo.

efficacy endpoints for both dose strengths of SYN-010 measured changes from baseline in abdominal pain, bloating and stool

frequency as well as the use of rescue medication relative to placebo.

Exploratory outcomes include adequate relief and quality

of life measures using the well-validated EQ-5D-5L and PAC-SYM patient questionnaires.

Enrollment in this study commenced in January 2019

2019 and remains ongoing.

Importantly, this study will aim to generate a comprehensive and meaningful data set to provide additional

insights and address specific queries into potential SYN-010 clinical efficacy, including dose response, length of treatment and

microbiome effects, intended to be evaluated in the FDA-agreed Phase 2b/3 adaptive design clinical program.

We believe outcomes

from this clinical trial are important to solidifying existing clinical outcomes data, and potentially simplifying and reducing

costs for future Phase 3 clinical development.

Generating such a data set requires rigorous screening criteria in order to obtain

reliable baseline parameters that includes foregoing current constipation interventions for a period of time prior to breath methane

This has proven challenging for a portion of prospective participants leading to higher than anticipated and inadvertent

patient-related screen-fail rates for IBS-C patients who presented at screening with breath-methane levels below the protocol-required

ten parts-per-million.

We recently met with the study investigators at Cedars-Sinai and following some discussion, we collectively

determined that generating a meaningful data set may be possible with a smaller patient population than previously anticipated.

However, in order to ensure the possibility of generating a meaningful data set of the highest quality with a smaller patient population,

the study investigators may elect to conduct a blinded interim or futility analysis in advance of a topline data readout to determine

whether the study is adequately powered and/or should continue as planned beyond the previously anticipated completion timeline.

We believe the successful completion of this study will allow us to re-engage with prospective partners, both domestically and

abroad, who found the results from our previously completed Phase 2 studies compelling and have indicated their interest in reviewing

a more robust and meaningful clinical data set.

During the fourth quarter of 2019, we engaged a well-known and

highly regarded consultancy group to conduct a commercial assessment of the IBS-C and Chronic Idiopathic Constipation (CIC) landscape

which we believe will serve to better inform strategic decision making as it relates to potential partnering and future commercialization

opportunities.

Initial findings from the commercial assessment indicate that while GIs and KOLs view IBS-C and CIC as similar but

separate disease states, they often treat both conditions utilizing nearly indistinguishable therapeutic interventions.

This presents

an interesting opportunity to potentially expand the SYN-010 addressable market as we believe SYN-010 can provide a therapeutic

benefit for CIC patients who test positive for elevated breath methane.

These findings may also have implications for future Phase

3 clinical development plans, as the inclusion of methane-positive CIC patients in future registration studies may allow for less

expensive and accelerated clinical trials.

1 An overall 12-week responder

is defined as a subject with a weekly response in at least 50% of the weeks of treatment (6 of 12 weeks).

Weekly Responder is defined

as a patient who experiences a decrease in weekly average score for worst abdominal pain in the past 24 hours of at least 30% compared

with Study 1 Baseline and a stool frequency increase of 1 or more CSBM per week compared with Study 1 Baseline.

Anticipated Regulatory Strategy

We believe that we will be able to utilize

the regulatory approval pathway provided in Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (the “FDCA”)

A New Drug Application (NDA) submitted under Section 505(b)(2), referred to as a 505(b)(2) NDA, allows some of the

information required for NDA approval, such as safety and efficacy information on the active ingredient, to come from studies not

conducted by or for the applicant and for which the applicant has not obtained a right of reference.

We believe we can rely in

part on the FDA’s previous findings of safety for Mevacor (lovastatin) in published clinical data.

We expect to rely on published

clinical trials using Mevacor to provide support of efficacy.

and was temporarily halted during the first and second quarter of 2020 due to the unique challenges posed by the global COVID-19

pandemic which required CSMC to temporarily limit all non-essential activities, directly impacting their ability to actively recruit

and screen new patients.

During the third quarter of 2020, a planned

interim futility analysis of the Phase 2b investigator-sponsored clinical study was completed.

Based on the review of the interim

analysis, it was concluded that although SYN-010 was well-tolerated, it failed to meet the prespecified efficacy criteria and was

unlikely to meet the primary objective of the study by the time enrollment was completed.

On September 30, 2020, CSMC formally

agreed to discontinue the study and on November 9, 2020 we and CSMC mutually agreed to terminate the Exclusive License Agreement.

CSMC has been unblinded and intends to conduct a comprehensive review of the data set and publish its findings.

Research Programs

Our research programs are primarily

directed to the development of GI acting products that have generated preclinical proof-of-concept with two pipeline products

(SYN-006 and SYN-007) that expand the potential utility of our beta-lactamase strategy.

We are also proceeding to an IND with

an unrelated oral enzyme product (SYN-020) with broad potential application to prevent and/or treat GI disease.

SYN-020 — Oral Intestinal

Alkaline Phosphatase (IAP)

SYN-020 is a quality-controlled, recombinant

version of Intestinal Alkaline Phosphatase (IAP) produced under cGMP conditions and formulated for oral delivery.

The published

literature indicates that IAP functions to diminish GI inflammation, tighten the gut barrier to diminish “leaky gut,”

and promote a healthy microbiome.

Based on these known mechanisms as well as our own supporting animal model data, we are developing

SYN-020 to mitigate the intestinal damage caused by radiation therapy that is routinely used to treat pelvic cancers, including

the treatment and prevention of radiation enteropathy secondary to cancer therapy as a first indication.

Despite its broad therapeutic

potential, a key hurdle to commercialization has been the high cost of IAP manufacture which is commercially available for as much

as $10,000 per gram.

We believe we have developed technologies to traverse this hurdle and now have the ability to produce more

than 3 grams per liter of SYN-020 for roughly a few hundred dollars per gram.

We are currently advancing a SYN-020 product candidate

through preclinical development and towards clinical trials.

During the second quarter of 2019, we completed a pre-IND meeting

with the FDA where we discussed nonclinical and clinical strategies and clarified requirements for IND-enabling toxicology studies

to evaluate safety and pharmacokinetics of SYN-020 in healthy volunteers.

During the fourth quarter of 2020, we made additional

progress towards the completion of IND-enabling toxicology studies and assay development that are expected to support the filing

of an IND for this program during the second quarter of 2020.

SYN-007 — Prevention

Our research programs are primarily directed

to the development of GI acting products that have generated preclinical proof-of-concept with two pipeline products (SYN-006 and

SYN-007) that expand the potential utility of our beta-lactamase strategy.

Our SYN-005 monoclonal antibody program is being developed

to both treat and prevent pertussis.

SYN-007 —

of CDI, overgrowth of pathogenic organisms and the emergence of antimicrobial resistance (AMR)

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The data from this canine study

were presented during recent microbiome conferences in 2017 and 2018.

Additional data was reported in 2019 from a dose-response

canine study which demonstrated SYN-007 mitigated antibiotic-mediated gut microbiome alteration and maintained gut microbiome integrity

were presented during microbiome conferences in 2017 and 2018.

Additional data was reported in 2019 from a dose-response canine

study which demonstrated SYN-007 mitigated antibiotic-mediated gut microbiome alteration and maintained gut microbiome integrity

when co-administered with oral amoxicillin.

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amoxicillin/clavulanate and also reduced the emergence of antibiotic resistance in a canine study.

Preclinical work in the canine

model is ongoing to optimize the dose of SYN-007.

SYN-006 — Prevention

Additional preclinical work

in the canine model will seek to optimize the dose of SYN-007.

SYN-006 —

of CDI, overgrowth of pathogenic organisms and the emergence of antimicrobial resistance (AMR)

SYN-006 has the potential to further

expand the utility of our SYN-004 (ribaxamase) program to a broader spectrum of IV beta-lactam antibiotics in the GI tract to

include carbapenem antibiotics.

Carbapenems are broad-spectrum beta-lactam antibiotics that have been shown to significantly

damage the gut microbiome, incur a high risk for C.

difficile infection, and enable GI overgrowth with multidrug

resistant organisms.

Carbapenems are frequently a last line of defense antibiotic, therefore the emergence and spread of

carbapenem resistance presents an urgent threat.

SYN-006 is a carbapenemase designed to degrade intravenous (IV) carbapenem

antibiotics within the GI tract to maintain the natural balance of the gut microbiome for the prevention of CDI, overgrowth

of pathogenic organisms and the emergence of antimicrobial resistance (AMR).

It is anticipated that, by protecting the gut

microbiome from exposure to carbapenem antibiotics, SYN-006 may potentially diminish the spread of such resistance.

Week 2017 conference, we presented a poster demonstrating SYN-006’s broad activity against four carbapenem antibiotics

as well as efficacy in a canine model.

The poster also showed data from a porcine model indicating that the carbapenem

ertapenem and potently damaged gut microbiomes and mediated expansion of antibiotic resistance genes in the GI tract.

successfully formulated SYN-006 for oral delivery and evaluated it in a porcine efficacy model in conjunction with IV

The data, presented at a clinical conference during the first quarter of 2018, demonstrated that SYN-006 did not

interfere with serum levels of ertapenem and did diminish antibiotic-mediated dysbiosis.

In addition to its potential ability

to prevent IV carbapenem-mediated CDI and AMR, additional clinical indications for SYN-006 could include prevention of

carbapenem-resistant Enterobacteriaceae (CRE) in cancer chemotherapy patients.

Carbapenems are a first-line treatment for

febrile neutropenia (FN) in hematologic cancer patients in China.

Infection by CRE is a recognized and increasing health

threat in China where the estimated CRE infection rate is between 10% and 20% in non-HCT chemotherapy patients and is

associated with high mortality.

In 2019, we reported additional supportive preclinical data demonstrating

SYN-006 attenuated emergence of antibiotic resistance in a pig model, including encoded beta-lactamases and genes conferring

resistance to a broad range of antibiotics such as aminoglycosides and macrolides.

SYN-005 — Pertussis

SYN-006 has the potential to further expand

the utility of our SYN-004 (ribaxamase) program to a broader spectrum of IV beta-lactam antibiotics in the GI tract to include

carbapenem antibiotics.

Carbapenems are broad-spectrum beta-lactam antibiotics that have been shown to significantly damage the

gut microbiome, incur a high risk for C.

difficile infection, and enable GI overgrowth with multidrug resistant organisms.

Carbapenems are frequently a last line of defense antibiotic, therefore the emergence and spread of carbapenem resistance presents

an urgent threat.

SYN-006 is a carbapenemase designed to degrade intravenous (IV) carbapenem antibiotics within the GI tract

to maintain the natural balance of the gut microbiome for the prevention of CDI, overgrowth of pathogenic organisms and the emergence

of antimicrobial resistance (AMR).

It is anticipated that, by protecting the gut microbiome from exposure to carbapenem antibiotics,

SYN-006 may potentially diminish the spread of such resistance.

At the ID Week 2017 conference, we presented a poster demonstrating

SYN-006’s broad activity against four carbapenem antibiotics as well as efficacy in a canine model.

The poster also showed

data from a porcine model indicating that the carbapenem ertapenem and potently damaged gut microbiomes and mediated expansion

of antibiotic resistance genes in the GI tract.

We have successfully formulated SYN-006 for oral delivery and evaluated it in a

porcine efficacy model in conjunction with IV ertapenem.

The data, presented at a clinical conference during the first quarter

of 2018, demonstrated that SYN-006 did not interfere with serum levels of ertapenem and did diminish antibiotic-mediated dysbiosis.

In addition to its potential ability to prevent IV carbapenem-mediated CDI and AMR, additional clinical indications for SYN-006

could include prevention of carbapenem-resistant Enterobacteriaceae (CRE) in cancer chemotherapy patients.

Carbapenems are a first-line

treatment for febrile neutropenia (FN) in hematologic cancer patients in China.

Infection by CRE is a recognized and increasing

health threat in China where the estimated CRE infection rate is between 10% and 20% in non-HCT chemotherapy patients and is associated with

high mortality.

In 2019, we reported additional supportive preclinical data demonstrating SYN-006 attenuated emergence of antibiotic

resistance in a pig model, including encoded beta-lactamases and genes conferring resistance to a broad range of antibiotics such

as aminoglycosides and macrolides.

SYN-005 —

(Whooping Cough)

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not yet fully vaccinated and exposure of individuals whose immunity has diminished over time.

According to the Centers for Disease Control

and Prevention (CDC), there were 24.1 million cases of whooping cough worldwide in 2014, and it is estimated that B.

infection causes up to 160,700 deaths each year worldwide, primarily among unvaccinated children younger than 5 years of age.

According to the Centers for Disease Control and Prevention (CDC), there are an estimated 24.1 million worldwide cases of whooping cough and about

160,700 deaths per year primarily among unvaccinated children younger than 5 years of age.

In April 2014, and again in September 2014,

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In September 2014, we received U.S.

Drug Designation from the FDA for SYN-005 for the treatment of pertussis.

In October 2015, the Bill & Melinda

Gates Foundation awarded a grant to UT Austin to generate preclinical proof-of-concept data in the neonatal non-human primate model

to test the hypothesis that antibody administration at birth may have a role in the prevention of pertussis.

In December 2015, the non-human primate

prophylaxis study was initiated by UT Austin to determine if administration of hu1B7, one component of SYN-005, at two days of

age could protect animals from a subsequent pertussis infection.

Orphan Drug Designation from the FDA for SYN-005 for the treatment of pertussis.

In October 2015, the Bill &

Melinda Gates Foundation awarded a grant to The University of Texas at Austin (UT Austin) to generate preclinical proof-of-concept

data in the neonatal non-human primate model to test the hypothesis that antibody administration at birth may have a role in the

prevention of pertussis.

In December 2015, the non-human

primate prophylaxis study was initiated by UT Austin to determine if administration of hu1B7, one component of SYN-005, at two

days of age could protect animals from a subsequent pertussis infection.

On April 19, 2017, we announced supportive

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patent estates that we either own or exclusively license.

Each potential product has issued patents that provide protection.

total, we have over 110 U.S.

In total, we have over 90 U.S.

and foreign patents and over 70 U.S.

and foreign patents pending.

The SYN-004 (ribaxamase) program

is supported by proprietary IP, namely U.S.

foreign patents pending.

The SYN-004 (ribaxamase) program is supported by IP that is assigned to Synthetic Biologics, namely U.S.

patents and foreign patents (in most major markets, e.g.

Europe (including Germany,

Great Britain and France), Japan, China and Canada, among others) and U.S.

Europe (including Germany, Great Britain and France), Japan, China and

Canada, among others) and U.S.

and foreign patents pending in most major markets, e.g.

Europe (including Germany, Great Britain and France), Japan, China and Canada, among others).

For instance, U.S.

and 9,587,234, which include claims to compositions of matter and pharmaceutical compositions of beta-lactamases, including SYN-004

(ribaxamase), have patent terms to at least 2031.

Further, U.S.

Patent 9,301,995 and 9,301,996, both of which will expire in 2031,

cover various uses of beta-lactamases, including SYN-004 (ribaxamase), in protecting the microbiome, and U.S.

9,376,673, 9,404,103, 9,464,280, and 9,695,409 which will expire in at least 2035, covers further beta-lactamase compositions of

matter related to SYN-004 (ribaxamase).

The SYN-010 program is supported by IP that is exclusively licensed to (and, in some cases

co-owned by) us, namely U.S.

patents and foreign patents (in most major markets, e.g.

Europe (including Germany, Great Britain

and France), and Canada, among others) and U.S.

and foreign patents pending in most major markets, e.g.

Europe (including Germany,

Great Britain and France), Japan, China and Canada, among others).

and France), Japan, China and Canada, among others).

For instance, U.S.

9,192,618, which expires in at

least 2023, includes claims that cover use of statins, including SYN-010, for the treatment of IBS-C.

which expires in at least 2033, includes claims that cover the use of a variety of compounds, including the active agent of SYN-010,

to treat constipation in certain screened patients.

9,744,208 covers methods of use of the active agent of SYN-010

for the treatment of constipation until at least 2034.

9,956,292 includes claims related to composition of matter

of anti-methanogenic compositions that find use in treating IBS-C and will expire in at least 2035.

8,894,994 and 9,587,234, which include claims

to compositions of matter and pharmaceutical compositions of beta-lactamases, including SYN-004 (ribaxamase), have patent terms

to at least 2031.

Further, U.S.

10,328,151, covers the composition of matter of the SYN-010 clinical agent and U.S.

Patent 10,519,515

covers methods of treating IBS-C with a statin, inclusive of SYN-010, in a selected patient

Patent 9,301,995 and 9,301,996, both of which will expire in 2031, cover various uses of beta-lactamases,

including SYN-004 (ribaxamase), in protecting the microbiome, and U.S.

9,290,754, 9,376,673, 9,404,103, 9,464,280,

and 9,695,409 which will expire in at least 2035, covers further beta-lactamase compositions of matter related to SYN-004 (ribaxamase).

The SYN-020 (oral intestinal alkaline phosphatase

(IAP)) program is supported by IP that is assigned to Synthetic Biologics, namely U.S.

and foreign patent applications (in many

major markets, e.g.

Europe, Canada, and Australia).

These patent applications, which cover various formulations, medical uses and

manufacture of SYN-020, are expected to expire in 2038-2040, if granted, and without taking potential patent term extensions or

patent term adjustment into account.

Our goal is to (i) obtain, maintain,

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our trade secrets, and (iii) operate without infringing on the proprietary rights of other parties worldwide.

We seek, where appropriate,

the broadest intellectual property protection for product candidates, proprietary information, and proprietary technology through

a combination of contractual arrangements and patents.

We seek, where

appropriate, the broadest intellectual property protection for product candidates, proprietary information, and proprietary technology

through a combination of contractual arrangements and patents.

Our Collaborations

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On December 5, 2013, through our majority

owned subsidiary, SYN Biomics, we entered into a worldwide exclusive license agreement (the “CSMC License Agreement”)

for the right to develop, manufacture, use, and sell products for the human and veterinary therapeutic and prophylactic treatments

for acute and chronic diseases.

An investigational team lead by Dr.

Mark Pimentel at CSMC has discovered that these products are

intended to target certain pathogenic GI microorganisms that are perceived as an underlying cause of diseases such as IBS-C, obesity

and type 2 diabetes.

The portfolio of intellectual property licensed to SYN Biomics under the CSMC License Agreement included nine

patents, 30 issued patents in various European countries, three issued Australian patents, one Canadian patent and

one issued Japanese patent as well as several pending U.S.

and international patent applications for most fields of use and modalities

subject to certain agreed-upon exceptions.

Under the terms of the CSMC License

Agreement we issued 9,569 unregistered shares of our common stock to CSMC, as payment of an initial license fee and patent

reimbursement fees of $150,000 and $220,000, respectively.

The parties also entered into a Stock Purchase Agreement with

respect to such stock issuance and other issuances of unregistered shares of our common stock that may be issued to CSMC in

lieu of cash, including license fees, milestone payments, expense reimbursements and option fees under the CSMC License

Commencing on the second anniversary of the CSMC License Agreement, SYN Biomics began paying an annual maintenance

fee, which payment is creditable against annual royalty payments owed under the CSMC License Agreement.

In addition to

royalty payments which are a percentage (in the low single digits and are subject to reduction under certain circumstances)

of Net Sales (as defined in the CSMC License Agreement) of Licensed Products (as defined in the CSMC License Agreement) and

Licensed Technology products (as defined in the CSMC License Agreement), SYN Biomics is obligated to pay CSMC a percentage of

any non-royalty sublicense revenues (ranging from 20% if prior to initiation of Phase 3 clinical trial to 15% if after

initiation of a Phase 3 clinical trial).

During the year ended December 31, 2016, SYN Biomics paid CSMC an aggregate of

$350,000 in milestone payments and is obligated to pay CSMC additional consideration up to $3,500,000 upon the achievement of

the following milestones (i) initiation of Phase 3 dosing for each additional indication of a Licensed Product or Licensed

The portfolio of intellectual property licensed to SYN Biomics under the CSMC License Agreement

included nine issued U.S.

patents, 30 issued patents in various European countries, three issued Australian patents, one Canadian

patent and one issued Japanese patent as well as several pending U.S.

and international patent applications for most fields of

use and modalities subject to certain agreed-upon exceptions.

Under the terms of the CSMC License Agreement

we issued 9,569 unregistered shares of our common stock to CSMC, as payment of an initial license fee and patent reimbursement

fees of $150,000 and $220,000, respectively.

The parties also entered into a Stock Purchase Agreement with respect to such stock

issuance and other issuances of unregistered shares of our common stock that may be issued to CSMC in lieu of cash, including license

fees, milestone payments, expense reimbursements and option fees under the CSMC License Agreement.

Commencing on the second anniversary

of the CSMC License Agreement, SYN Biomics began paying an annual maintenance fee, which payment was creditable against annual royalty

payments owed under the CSMC License Agreement.

In addition to royalty payments which are a percentage (in the low single digits

and are subject to reduction under certain circumstances) of Net Sales (as defined in the CSMC License Agreement) of Licensed Products

(as defined in the CSMC License Agreement) and Licensed Technology products (as defined in the CSMC License Agreement), SYN Biomics

was obligated to pay CSMC a percentage of any non-royalty sublicense revenues (ranging from 20% if prior to initiation of Phase

3 clinical trial to 15% if after initiation of a Phase 3 clinical trial).

During the year ended December 31, 2016, SYN Biomics

paid CSMC an aggregate of $350,000 in milestone payments and was obligated to pay CSMC additional consideration up to $3,500,000

upon the achievement of the following milestones (i) initiation of Phase 3 dosing for each additional indication of a Licensed

Product or Licensed Technology Product;

(ii) successful Phase 3 trial completion for each Licensed Product and each Licensed

Technology Product;

(ii) successful Phase 3 trial completion for each Licensed Product and each Licensed Technology Product;

(iii) the FDA’s acceptance of a New Drug Application for each Licensed Product and each Licensed Technology Product;

(iii) the FDA’s acceptance of a New Drug Application for each Licensed Product and each Licensed

Technology Product;

(iv) regulatory approval for each Licensed Product and each Licensed Technology Product;

and (vi) the first commercial sale

of each Licensed Product and each Licensed Technology Product.

There were no milestone payments made during years ended

December 31, 2019 and 2018.

The CSMC License Agreement terminates:

(i) automatically if SYN Biomics enters into a liquidating bankruptcy or other specified bankruptcy event or if the performance

of any term, covenant, condition or provision of the CSMC License Agreement will jeopardize the licensure of CSMC, its participation

in certain reimbursement programs, its full accreditation by the Joint Commission of Accreditation of Healthcare Organizations

or any similar state organizations, its tax exempt status or is deemed illegal;

(ii) upon 30 days’ notice from CSMC if SYN

Biomics fails to make a payment or use commercially reasonable efforts to exploit the patent rights;

(iii) upon 60 days’

notice from CSMC if SYN Biomics fails to cure any breach or default of any material obligations under the CSMC License Agreement;

or (iv) upon 90 days’ notice from SYN Biomics if CSMC fails to cure any breach or default of any material obligations under

the CSMC License Agreement.

SYN Biomics also has the right to terminate the License Agreement without cause upon 6 months’

notice to CSMC.

first commercial sale of each Licensed Product and each Licensed Technology Product.

There were no milestone payments made during

the years ended December 31, 2020 and 2019.

Prior to the execution of the CSMC License

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Mark Pimentel (the primary inventor

of the intellectual property), representing 11.5% and 8.5%, respectively, of the outstanding shares of SYN Biomics (the “SYN

Biomics Shares”).

of the intellectual property), representing 11.5% and 8.5%, respectively, of the outstanding shares of SYN Biomics (the “SYN

Biomics Shares”).

The Stock Purchase Agreements for the SYN Biomics Shares provide for certain anti-dilution protection until

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approval, as of the 18 and 36 month anniversary date of the effective date of the Stock Purchase Agreements, for each of CSMC and

Pimentel to exchange up to 50% of their SYN Biomics Shares for unregistered shares of our common stock, with the rate of exchange

based upon the relative contribution of the valuation of SYN Biomics to the public market valuation of us at the time of each exchange.

The Stock Purchase Agreements also provide for tag-along rights in the event of the sale by us of our shares of SYN Biomics.

On August 29, 2015, we, SYN Biomics and

Pimentel entered into the Pimentel Amendment to the Pimentel Stock Purchase Agreement entered into on December 3, 2013, which

accelerated the date upon which Dr.

Pimentel can exchange his shares of common stock in SYN Biomics for shares of our common stock.

Pimentel to exchange up to 50% of their SYN Biomics Shares for unregistered shares of our common stock, with the rate

of exchange based upon the relative contribution of the valuation of SYN Biomics to the public market valuation of us at the time

of each exchange.

The Stock Purchase Agreements also provide for tag-along rights in the event of the sale by us of our shares

of SYN Biomics.

On August 29, 2015, Dr.

Pimentel notified us of his intent to exchange all of the shares of common stock in SYN Biomics owned by

him for 38,572 shares of our common stock in accordance with the terms of the Pimentel Stock Purchase Agreement, as amended and

the exchange was effectuated on August 31, 2015.

We filed a “resale” registration statement to register 5,715 shares

issued to Dr.

Pimentel, which was declared effective by the SEC on October 15, 2015.

On September 5, 2018, we entered into an

agreement with CSMC for CSMC to conduct an investigator-sponsored Phase 2 clinical study of SYN-010 to be co-funded by us and CSMC

(the “Study”).

The Study will provide further evaluation of the efficacy and safety of SYN-010.

Pimentel notified us of his

intent to exchange all of the shares of common stock in SYN Biomics owned by him for 38,572 shares of our common stock in accordance

with the terms of the Pimentel Stock Purchase Agreement, as amended and the exchange was effectuated on August 31, 2015.

We filed a “resale”

registration statement to register 5,715 shares issued to Dr.

Pimentel, which was declared

effective by the SEC on October 15, 2015.

On September 5, 2018, we entered into

an agreement with CSMC for CSMC to conduct an investigator-sponsored Phase 2 clinical study of SYN-010 to be co-funded by us and

CSMC (the “Study”).

In consideration of the support provided

by CSMC for the Study, we entered into a Stock Purchase Agreement with CSMC pursuant to which we:

(i) issued to CSMC fifty thousand

(50,000) shares of our common stock;

(i) issued to CSMC fifty

thousand (50,000) shares of our common stock;

and (ii) transferred to CSMC an additional two million four hundred twenty thousand

(2,420,000) shares of common stock of its SYN Biomics, Inc.

owned by us, such that after such issuance CSMC owns an aggregate of seven million

four hundred eighty thousand (7,480,000) shares of common stock of SYN Biomics, representing seventeen percent (17%) of the issued

and outstanding shares of SYN Biomics’ common stock.

The Agreement also provides CSMC with

a right, commencing on the six month anniversary of issuance of the stock under certain circumstances in the event that the

shares of stock of SYN Biomics are not then freely tradeable, and subject to NYSE American, LLC approval, to exchange its SYN

Biomics shares for unregistered shares of our common stock, with the rate of exchange based upon the relative contribution of

the valuation of SYN Biomics to the public market valuation of our company at the time of each exchange all subject to

approval of the NYSE American, LLC.

The Stock Purchase Agreement also provides for tag-along rights in the event of the sale

by us of our shares of SYN Biomics.

owned by us, such that after such issuance CSMC owns an aggregate

of seven million four hundred eighty thousand (7,480,000) shares of common stock of SYN Biomics, representing seventeen percent

(17%) of the issued and outstanding shares of SYN Biomics’

common stock.

The Stock Purchase Agreement also provides

CSMC with a right, commencing on the six month anniversary of issuance of the stock under certain circumstances in the event that

the shares of stock of SYN Biomics are not then freely tradeable, and subject to NYSE American, LLC approval, to exchange its SYN

Biomics shares for unregistered shares of our common stock, with the rate of exchange based upon the relative contribution of the

valuation of SYN Biomics to the public market valuation of our company at the time of each exchange all subject to approval

of the NYSE American, LLC.

The Stock Purchase Agreement also provides for tag-along rights in the event of the sale by us of our

shares of SYN Biomics.

During the third quarter of 2020, a planned

interim futility analysis of the Phase 2b investigator-sponsored clinical study was completed.

Based on the review of the interim

analysis, it was concluded that although SYN-010 was well-tolerated, it failed to meet the prespecified efficacy criteria and was

unlikely to meet the primary objective of the study by the time enrollment is completed.

On September 30, 2020 CSMC formally

agreed to discontinue the study and on November 9, 2020, we and CSMC mutually agreed to terminate the Exclusive License Agreement.

CSMC has been unblinded and intends to conduct a comprehensive review of the data set and publish its findings.

Washington University School of Medicine in St.

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Trial Agreement

In August 7, 2019, we entered into a clinical

trial agreement (“CTA”) with Washington University School of Medicine in St.

Louis (“Washington University”)

In August 7, 2019, we entered into

a clinical trial agreement (“CTA”) with Washington University School of Medicine in St.

Louis (“Washington University”)

to conduct a Phase 1b/2a single-center, randomized, double-blinded, placebo-controlled clinical trial designed to evaluate the

safety, tolerability and pharmacokinetics of oral SYN-004 (ribaxamase) in up to 36 adult allogeneic hematopoietic cell transplant

(HCT) recipients (the “Study”).

Under the terms of the CTA, we will serve as the sponsor of the Study and supply SYN-004

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of the study is withdrawn by the FDA;

(ii) if the emergence of any adverse reaction or side effect with SYN-004 (ribaxamase) administered

in the Study is of such magnitude or incidence in the opinion of either party to support termination;

or (iii) upon a breach of

the terms of the CTA if the breaching party fails to cure the breach within 30 days after receipt of notice.

We have the right

to terminate the CTA (i) effective immediately if Washington University fails to perform the study in accordance with the terms

of the protocol, the CTA or applicable laws or regulations or if Washington University or the principal investigator become debarred

or (ii) upon 14 days written notice and Washington University has the right to terminate the CTA upon 14 days notice if the principal

investigator becomes unable to perform or complete the Study and the parties have not, prior to the expiration of such fourteen

(14) day period, agreed to an alternative principal investigator.

(ii) if the emergence of any adverse reaction or side effect with SYN-004 (ribaxamase)

administered in the Study is of such magnitude or incidence in the opinion of either party to support termination;

or (iii) upon

a breach of the terms of the CTA if the breaching party fails to cure the breach within 30 days after receipt of notice.

the right to terminate the CTA (i) effective immediately if Washington University fails to perform the study in accordance

with the terms of the protocol, the CTA or applicable laws or regulations or if Washington University or the principal investigator

become debarred or (ii) upon 14 days written notice and Washington University has the right to terminate the CTA upon 14 days

notice if the principal investigator becomes unable to perform or complete the Study and the parties have not, prior to the expiration

of such fourteen (14) day period, agreed to an alternative principal investigator.

Massachusetts General Hospital Exclusive

Option License Agreement

On May 27, 2020, we entered into an

agreement with Massachusetts General Hospital (“MGH”) granting us an option for an exclusive license to intellectual

property and technology related to the use of intestinal alkaline phosphatase (“IAP”) to maintain gastrointestinal

(GI) and microbiome health, diminish systemic inflammation, and treat age-related diseases.

If executed, we plan to use this license

in the advancement of an expanded clinical development program for SYN-020, our proprietary recombinant version of bovine IAP currently

in pre-clinical development.

Under the terms of the agreement, Synthetic Biologics is granted exclusive rights to negotiate a worldwide

license with MGH to commercially develop SYN-020 to treat and prevent metabolic and inflammatory diseases associated with aging.

The University of Texas at Austin License

Agreement and Sponsored Research Agreement

On December 19, 2012, we entered into a

Patent License Agreement (the “Texas License Agreement”) with UT Austin for the exclusive license of the right to use,

develop, manufacture, market and commercialize certain research and patents related to pertussis antibodies developed in the lab

On December 19, 2012, we entered into

a Patent License Agreement (the “Texas License Agreement”) with UT Austin for the exclusive license of the right to

use, develop, manufacture, market and commercialize certain research and patents related to pertussis antibodies developed in the

Maynard, Associate Professor of Chemical Engineering.

In accordance with the terms of the Texas License Agreement

we made the following payments to the UT Austin:

a payment of past patent expenses, an annual payment of $50,000 per year commencing

on the effective date through December 31, 2014 and a $25,000 payment on December 31, 2015.

The Texas License Agreement also provides

that UT Austin is entitled to milestone payments of $50,000 upon commencement of Phase 1 Clinical Trials, $100,000 upon commencement

of Phase 3 Clinical Trials, $250,000 upon NDA submission in the United States, $100,000 upon European Medicines Agency approval

and $100,000 upon regulatory approval in an Asian country.

In addition, the University is entitled to a running royalty upon Net

Product Sales and Net Service Sales (as defined in the Texas License Agreement and currently projected to be 2037 (not accounting

for possible extensions)).

The License Agreement terminates upon the expiration of the patent rights (as defined in the Texas License

provided, however that the Texas License Agreement is subject to early termination by us in our discretion and by the

University for a breach of the Texas License Agreement by us.

In connection with the Texas License

Agreement, we also entered into a Sponsored Research Agreement (the “Sponsored Research Agreement”) with the

University pursuant to which the University will perform certain research work related to pertussis under the direction of

In accordance with the terms of the Texas License

Agreement we made the following payments to the UT Austin:

a payment of past patent expenses, an annual payment of $50,000 per

year commencing on the effective date through December 31, 2014 and a $25,000 payment on December 31, 2015.

License Agreement also provides that UT Austin is entitled to milestone payments of $50,000 upon commencement of Phase 1 Clinical

Trials, $100,000 upon commencement of Phase 3 Clinical Trials, $250,000 upon NDA submission in the United States, $100,000 upon

European Medicines Agency approval and $100,000 upon regulatory approval in an Asian country.

In addition, the University is entitled

to a running royalty upon Net Product Sales and Net Service Sales (as defined in the Texas License Agreement and currently projected

to be 2037 (not accounting for possible extensions)).

The License Agreement terminates upon the expiration of the patent rights

(as defined in the Texas License Agreement);

provided, however that the Texas License Agreement is subject to early termination

by us in our discretion and by the University for a breach of the Texas License Agreement by us.

In connection with the Texas License Agreement,

we also entered into a Sponsored Research Agreement (the “Sponsored Research Agreement”) with the University pursuant

to which the University will perform certain research work related to pertussis under the direction of Dr.

Jennifer Maynard.

All inventions conceived during such research shall be subject to the Texas License Agreement and we

will obtain certain rights to patents and technology developed during the course of such research.

We paid the University a

fixed fee for the first year of $303,287 and the second and third years of $316,438 and $328,758, respectively.

The Sponsored

Research Agreement was amended on October 22, 2015, to extend its termination date to January 15, 2017, on September 2, 2016

to extend the agreement until January 15, 2018;

on August 22, 2017 to extend the agreement until January 17, 2019;

All inventions conceived during such research shall be subject to the Texas License Agreement and we will obtain certain rights

to patents and technology developed during the course of such research.

We paid the University a fixed fee for the first year of

$303,287 and the second and third years of $316,438 and $328,758, respectively.

The Sponsored Research Agreement was amended on

October 22, 2015, to extend its termination date to January 15, 2017, on September 2, 2016 to extend the agreement

until January 15, 2018;

on August 22, 2017 to extend the agreement until January 17, 2019;

provided, however, the Sponsored Research Agreement is

subject to early termination upon the written agreement of the parties, a default in the material obligations under the

Sponsored Research Agreement which remain uncured for 60 days after receipt of notice, automatically upon our bankruptcy or

insolvency and by us in our sole discretion at any time after the one year anniversary of the date of execution thereof upon

no less than 90 days’ notice.

Upon a termination or due to a breach by the University, we are only be responsible for

all reasonable expenses that do not exceed the fixed annual amount and that are incurred by the University prior to the

termination date for services performed prior to the termination date.

on August 24, 2018

to extend the agreement until January 21, 2021;

and again on August 18, 2020 which extended the agreement until January 17,

provided, however, the Sponsored Research Agreement is subject to early termination upon the written agreement of the parties,

a default in the material obligations under the Sponsored Research Agreement which remain uncured for 60 days after receipt of

notice, automatically upon our bankruptcy or insolvency and by us in our sole discretion at any time after the one year anniversary

of the date of execution thereof upon no less than 90 days’

Upon a termination or due to a breach by the University,

we will only be responsible for all reasonable expenses that do not exceed the fixed annual amount and that are incurred by the

University prior to the termination date for services performed prior to the termination date.

We have an issued U.S.

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pertussis mAbs licensed from UT Austin.

Oral Enzyme for C.

difficile Program

Acquisition Agreement

On November 8, 2012, we entered into an

Asset Purchase Agreement (the “Prev Agreement”) with Prev ABR LLC (“Prev”), and subsequently closed the

transaction on November 28, 2012.

Pursuant to the Prev Agreement we acquired the C.

difficile program assets of Prev, including

pre-IND package for P3A (SYN-004), Phase 1 and Phase 2 clinical data for P1A, manufacturing processes and data, and a portfolio

of issued and pending U.S.

and international patents intended to support an IND and BLA with the FDA.

Pursuant to the Prev Agreement,

we paid Prev an initial cash payment of $100,000 upon execution of the Prev Agreement, at closing paid an additional cash payment

of $135,000 and issued 17,858 unregistered shares of our common stock to Prev and issued Prev an aggregate of 18,724 shares of

our common stock upon achievement of the first three milestones.

In addition, upon the achievement of the milestones set forth

below, Prev may be entitled to receive additional consideration up to $13 million payable 50% in cash and 50% in our stock, subject

to Prev’s option to receive the entire payment in shares of our stock:

(i) upon commencement of a Phase 3 clinical trial;

(ii) upon Biologic License Application (BLA) filing in the U.S.

and for territories outside of the U.S.

(as defined in the Prev

and (iii) upon BLA approval in the U.S.

and upon approval in territories outside the U.S.

No royalties are payable

to Prev under the Prev Agreement.

The Prev Agreement also provided that Prev

had a right to the return to it of all assets acquired by us under the Prev Agreement if certain clinical developments were not

achieved, all of which were achieved and therefore Prev no longer has a right to the return of its assets.

Infectious Disease Collaboration with

Intrexon Corporation

On August 6, 2012, we entered into an Exclusive

Channel Collaboration (“ECC”) with Intrexon (the “Infectious Disease ECC”) that governs a “channel

collaboration” arrangement in which we intend to use Intrexon’s technology relating to the identification, design and

production of human antibodies and DNA vectors for the development and commercialization of a series of human recombinant monoclonal

antibody therapies for the treatment of pertussis (the “Field’) .

Such license is exclusive with respect to any

clinical development, selling, offering for sale or other commercialization of our products within the Field (“Synthetic

Products”), and otherwise is non-exclusive.

We may not sublicense the rights described without Intrexon’s written consent.

On August 6, 2012, we entered into

an Exclusive Channel Collaboration (“ECC”) with Intrexon (the “Infectious Disease ECC”) that governs a

“channel collaboration”

arrangement in which we intend to use Intrexon’s technology relating to the identification,

design and production of human antibodies and DNA vectors for the development and commercialization of a series of human recombinant

monoclonal antibody therapies for the treatment of pertussis (the “Field”) .

Such license is exclusive with respect

to any clinical development, selling, offering for sale or other commercialization of our products within the Field (“Synthetic

Products”), and otherwise is non-exclusive.

We may not sublicense the rights described without Intrexon’s written consent.

Under the Infectious Disease ECC, and subject to certain exceptions, we are responsible for, among other things, the performance

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Intrexon may also terminate the Infectious Disease ECC if we elect not to

pursue the development of a Program identified by Intrexon that is a “Superior Therapy” as defined in the Infectious

Disease ECC upon 60 days’ notice unless we remedy the circumstances giving rise to the termination during such notice period.

Each party has the right to terminate the agreement upon 60 days’ notice if the other party commits a material breach of

pursue the development of a Program identified by Intrexon that is a “Superior Therapy”

as defined in the Infectious

Disease ECC upon 60 days’

notice unless we remedy the circumstances giving rise to the termination during such notice period.

Each party has the right to terminate the agreement upon 60 days’

notice if the other party commits a material breach of

the Infectious Disease ECC, subject to certain cure periods.

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is a subject of an application for regulatory approval that is pending before the applicable regulatory authority;

is a subject of at least a Phase 2 or Phase 3 clinical trial if such termination is by Intrexon due to a material breach by us of the Infectious Disease ECC or by us upon 60 days’ notice after the first 18 months.

is a subject of at least a Phase 2 or Phase 3 clinical trial if such termination is by Intrexon due to a material breach by us of the Infectious Disease ECC or by us upon 60 days’

notice after the first 18 months.

Our obligation to pay the royalties described

above with respect to these “retained” products will survive termination of the Infectious Disease ECC.

above with respect to these “retained”

products will survive termination of the Infectious Disease ECC.

In the event of a termination of the Infectious

Disease ECC, product candidates that are generating revenue or being considered for approval by the applicable regulatory body

or have been approved by the applicable governing body (“Infectious Disease Retained Products”) at the time of the

Infectious Disease ECC’s termination are retained by us, subject to Intrexon’s right to receive royalty payments.

or have been approved by the applicable governing body (“Infectious Disease Retained Products”) at the time of the

Infectious Disease ECC’s termination are retained by us, subject to Intrexon’s right to receive royalty payments.

as necessary for us to continue to obtain regulatory approval for or commercialize any Infectious Disease Retained Product, in

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shares of our common stock as consideration in connection with the Infectious Disease ECC and the related Stock Issuance Agreement

with Intrexon that we entered into on August 6, 2012 (the “Second Stock Issuance Agreement”).

We also agreed upon the filing of an IND

application with the FDA for a Synthetic Product, or alternatively the filing of the first equivalent regulatory filing with a

foreign regulatory agency (both as applicable, the “IND Milestone Event”), to pay Intrexon either (i) $2.0 million

in cash, or (ii) that number of shares of Common Stock (the “IND Milestone Shares”) having a fair market value equaling

$2.0 million where such fair market value is determined using published market data of the share price for Common Stock at the

close of market on the business day immediately preceding the date of public announcement of attainment of the IND Milestone Event.

foreign regulatory agency (both as applicable, the “IND Milestone Event”), to pay Intrexon either (i) $2.0 million

in cash, or (ii) that number of shares of Common Stock (the “IND Milestone Shares”) having a fair market value

equaling $2.0 million where such fair market value is determined using published market data of the share price for Common Stock

at the close of market on the business day immediately preceding the date of public announcement of attainment of the IND Milestone

Upon the first to occur of either first

commercial sale of a Synthetic Product in a country or the granting of the regulatory approval of that Synthetic Product (both

as applicable, the “Approval Milestone Event”), we agreed to pay to Intrexon either (i) $3.0 million in cash, or (ii)

that number of shares of Common Stock (the “Approval Milestone Shares”) having a fair market value equaling $3.0 million

where such fair market value is determined using published market data of the share price for Common Stock at the close of market

on the business day immediately preceding the date of public announcement of attainment of the Approval Milestone Event.

pay Intrexon royalties on annual net sales of products, calculated on a product-by-product basis, equal to a percent of net sales

of Synthetic Products (ranging from mid-single digits on the first $100 million of net sales to mid-teen digits on net sales in

excess of $100 million).

We have likewise agreed to pay Intrexon a percentage of quarterly revenue obtained from a sublicensor

in the event of a sublicensing arrangement.

as applicable, the “Approval Milestone Event”), we agreed to pay to Intrexon either (i) $3.0 million in cash,

or (ii) that number of shares of Common Stock (the “Approval Milestone Shares”) having a fair market value equaling

$3.0 million where such fair market value is determined using published market data of the share price for Common Stock at the

close of market on the business day immediately preceding the date of public announcement of attainment of the Approval Milestone

We will pay Intrexon royalties on annual net sales of products, calculated on a product-by-product basis, equal to a percent

of net sales of Synthetic Products (ranging from mid-single digits on the first $100 million of net sales to mid-teen digits on

net sales in excess of $100 million).

We have likewise agreed to pay Intrexon a percentage of quarterly revenue obtained from a

sublicensor in the event of a sublicensing arrangement.

In connection with the transactions contemplated

by the Second Stock Issuance Agreement, and pursuant to the First Amendment to Registration Rights Agreement executed and delivered

by the parties at the closing, we filed a “resale” registration statement registering the resale of certain of the

by the parties at the closing, we filed a “resale”

registration statement registering the resale of certain of the

shares issued under the Second Stock Issuance Agreement.

Manufacturing

Our product candidates are biologics

and small molecules that can be readily synthesized by processes that we have developed;

however, our manufacturing for our

clinical programs, including SYN-004, SYN-010 and SYN-020 may require long lead times.

We do not own or operate manufacturing

facilities for the production of our product candidates for preclinical and clinical quantities.

We rely on third-party

contract manufacturers, and in most cases only one third-party, to manufacture critical raw materials, drug substance and

final drug product for our research, preclinical development and clinical trial activities.

Commercial quantities of any

drugs we seek to develop will have to be manufactured in facilities and by processes that comply with the FDA and other

regulations, and we plan to rely on third parties to manufacture commercial quantities of products we successfully

Our product candidates are biologics that

can be readily synthesized by processes that we have developed;

however, the manufacturing for our clinical programs, including

SYN-004 and SYN-020 may require long lead times.

We do not own or operate manufacturing facilities for the production of our product

candidates for preclinical and clinical activities.

We rely on third-party contract manufacturers, and in most cases only one third-party,

to manufacture critical raw materials, drug substance and final drug product for our research, preclinical development and clinical

trial activities.

Commercial quantities of any drugs we seek to develop will have to be manufactured in facilities and by processes

that comply with the FDA and other regulations, and we plan to rely on third parties to manufacture commercial quantities of products

we successfully develop through FDA approval.

Although we believe we have sufficient quantities of SYN-004 and SYN-020 to complete

our planned Phase 1b/2a clinical trial of SYN-004 and our planned Phase 1 clinical trials of SYN-020, we do not currently have

a definitive agreement with any third-party vendors for the manufacture of additional quantities of SYN-004 and SYN-020 for potential

future clinical trials.

Research and Development

During the years ended December 31,

and 2018, we incurred approximately $11.1 million, $11.8 million, respectively, in research and development expenses.

2020 and 2019, we incurred approximately $5.1 million and $11.1 million, respectively, in research and development expenses.

Government Regulation

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investigators in accordance with good clinical practice (GCP) regulations, which include informed consent requirements.

must be approved and monitored by the appropriate Institutional Review Boards (IRBs) which are periodically informed of the study’s

progress, adverse events and changes in research.

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and establish dosage tolerance and optimal dosage.

When Phase 2 evaluations

demonstrate that a dosage range is effective with an acceptable safety profile, Phase 3 trials to further evaluate dosage, clinical

efficacy and safety, are undertaken in an expanded patient population, often at geographically dispersed sites.

evaluations demonstrate that a dosage range is effective with an acceptable safety profile, Phase 3 trials to further evaluate

dosage, clinical efficacy and safety, are undertaken in an expanded patient population, often at geographically dispersed sites.

We cannot be certain that we will successfully

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The FDA reviews each NDA or BLA submitted and may request additional

A 60-day period after the sponsor’s submission of an NDA or BLA is used by the FDA to determine whether the

application is sufficiently complete to permit substantive review, in which case the application is accepted for filing.

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GMPs and with manufacturing commitments made in the application.

Submission of an NDA or BLA with

clinical data requires payment of a substantial fee.

In return, the FDA assigns a goal for review and decision on the

application, in which the FDA may approve or deny the NDA or BLA, or issue a complete response letter outlining information

needed to support approval, including a potential need for additional clinical data.

Even if these data are submitted, the

FDA may ultimately decide the NDA or BLA does not satisfy approval criteria.

If the FDA approves the NDA or BLA, the product

becomes available for marketing.

Product approval may be withdrawn if regulatory compliance is not maintained or safety

problems occur.

The FDA may require post-marketing studies, also known as Phase 4 studies, as a condition of approval, and

Risk Evaluation and Mitigation Strategies (REMS) requires surveillance programs to monitor approved products that have been

commercialized.

The agency has the power to require changes in labeling or prohibit further marketing based on the results of

post-marketing surveillance.

Submission of an NDA or BLA with clinical

data requires payment of a substantial fee.

In return, the FDA assigns a goal for review and decision on the application, in which

the FDA may approve or deny the NDA or BLA, or issue a complete response letter outlining information needed to support approval,

including a potential need for additional clinical data.

Even if these data are submitted, the FDA may ultimately decide the NDA

or BLA does not satisfy approval criteria.

If the FDA approves the NDA or BLA, the product becomes available for marketing.

approval may be withdrawn if regulatory compliance is not maintained or safety problems occur.

The FDA may require post-marketing

studies, also known as Phase 4 studies, as a condition of approval, and Risk Evaluation and Mitigation Strategies (REMS) requires

surveillance programs to monitor approved products that have been commercialized.

The agency has the power to require changes in

labeling or prohibit further marketing based on the results of post-marketing surveillance.

Satisfaction of these and other regulatory

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on our business.

The FDA’s policies may change, and

additional government regulations may be enacted which could prevent or delay regulatory approval of our potential products.

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or administrative action, either in the U.S.

Section 505(b)(2) NDAs

NDAs for most new drug products generally

are based on two full clinical studies which must contain substantial evidence of the safety and efficacy of the proposed new product.

These applications are submitted under Section 505(b)(1) of the FDCA.

The FDA is, however, authorized to approve an alternative

type of NDA under Section 505(b)(2) of the FDCA.

This type of application allows the applicant to rely, in part, on the FDA’s

previous findings of safety and efficacy for the active moiety, or published literature, where such studies were not conducted

by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom

the investigations were conducted.

We believe that we will be able to utilize the regulatory approval pathway provided in Section

505(b)(2) of the FDCA for SYN-010.

Orphan Drug Act

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of the regulatory review or approval process, but does provide certain advantages, such as a waiver of Prescription Drug User Fee

Act, or PDUFA, fees, enhanced access to FDA staff and potential waiver of pediatric research requirements.

If a product that has orphan drug

designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is

entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full

NDA, to market the same drug or biologic for the same indication for seven years, except in limited circumstances, such as a

showing of clinical superiority to the product with orphan drug exclusivity.

Orphan drug exclusivity does not prevent FDA

from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different

disease or condition.

Among the other benefits of orphan drug designation are tax credits for certain research and a waiver

of the application user fee.

A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use

that is broader than the indication for which it received orphan designation.

In addition, exclusive marketing rights in the

United States may be lost if the FDA later determines that the request for designation was materially defective or if the

manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or

Act (“PDUFA”), fees, enhanced access to FDA staff and potential waiver of pediatric research requirements.

If a product that has orphan drug designation

subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan

product exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to market the same

drug or biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority

to the product with orphan drug exclusivity.

Orphan drug exclusivity does not prevent FDA from approving a different drug or biologic

for the same disease or condition, or the same drug or biologic for a different disease or condition.

Among the other benefits

of orphan drug designation are tax credits for certain research and a waiver of the application user fee.

A designated orphan drug

may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan

In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request

for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet

the needs of patients with the rare disease or condition.

Other Healthcare Laws and Compliance Requirements

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HIPAA and its implementing regulations also established uniform federal standards

for certain “covered entities” (healthcare providers, health plans and healthcare clearinghouses) governing the conduct

for certain “covered entities”

(healthcare providers, health plans and healthcare clearinghouses) governing the conduct

of certain electronic healthcare transactions and protecting the security and privacy of protected health information.

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injunctions, recall or seizure of products, total or partial suspension of production, denial or withdrawal of pre-marketing product

approvals, private “qui tam” actions brought by individual whistleblowers in the name of the government or refusal

approvals, private “qui tam”

actions brought by individual whistleblowers in the name of the government or refusal

to allow us to enter into supply contracts, including government contracts, and the curtailment or restructuring of our operations,

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Actelion Pharmaceutical

Ltd., Assembly Biosciences, Inc., AzurRx, Inc., Da Volterra, Pfizer Inc., Merck & Co.

Inc., Merus B.V., Pfizer Inc., Rebiotix,

Inc., Seres Therapeutics, Inc., Summit Therapeutics plc.

Ltd., Artugen Therapeutics, Inc., AzurRx, Inc., Da Volterra, Deinove, Pfizer Inc., Merck & Co.

Inc., Merus B.V.,

Pfizer Inc., Rebiotix, Inc., Seres Therapeutics, Inc., Summit Therapeutics plc.

and Vedanata Biosciences Inc.

Companies that sell or are developing products

for the treatment or prevention of acute graft-versus-host-disease (aGVHD) include:

Amgen, Inc., Astellas Pharma, Janssen Biotech,

Inc., Mallinckrodt plc, Novartis International AG, Pfizer, Inc.

and Roche AG..

Companies that currently sell or are developing

proprietary products for IBS-C include:

Ardelyx, Inc., Allergan plc, Bausch Health Companies Inc., Ironwood Pharmaceuticals, Inc.,

and Takeda Pharmaceutical Company Limited.

Companies that currently sell or are developing proprietary products for pertussis include:

GlaxoSmithKline plc, MitsubishiTanabe Pharma Corporation and Sanofi S.A.

that sell or are developing products for the treatment or prevention of acute graft-versus-host-disease (aGVHD) include:

Astellas Pharma, Janssen Biotech, Inc., Mallinckrodt plc, Novartis International AG, Pfizer, Inc.

Roche AG and Takeda

Pharmaceutical Company Ltd.

Academic research centers, governmental

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Corporate History

Our predecessor, Sheffield Pharmaceuticals,

Inc., was incorporated in 1986, and in 2006 engaged in a reverse merger with Pipex Therapeutics, Inc., a publicly-traded Delaware

Our predecessor, Sheffield Pharmaceuticals, Inc.,

was incorporated in 1986, and in 2006 engaged in a reverse merger with Pipex Therapeutics, Inc., a publicly-traded Delaware

corporation formed in 2001.

After the merger, we changed our name to Pipex Pharmaceuticals, Inc., and in October 2008 we changed

our name to Adeona Pharmaceuticals, Inc.

On October 15, 2009, we engaged in a merger with a wholly owned subsidiary for the purpose

of reincorporating in the State of Nevada.

After the merger, we changed our name to Pipex Pharmaceuticals, Inc., and in October 2008

we changed our name to Adeona Pharmaceuticals, Inc.

On October 15, 2009, we engaged in a merger with a wholly owned subsidiary

for the purpose of reincorporating in the State of Nevada.

On February 15, 2012, we changed our name to Synthetic Biologics, Inc.

On August 10,

2018, we effected a one for thirty-five reverse stock split of our authorized, issued and outstanding common stock.

As of February 20, 2020, we employed approximately

11 individuals, all of whom are full-time employees.

A significant number of our management and professional employees have had

prior experience with pharmaceutical, biotechnology or medical product companies.

None of our employees are covered by collective

bargaining agreements, and management considers relations with our employees to be in good standing.

On August 10, 2018, we effected a one for thirty-five reverse stock split of our authorized, issued and outstanding common

Human Capital-Employees

believe that our success depends upon our ability to attract, develop and retain key personnel.

As of March 3, 2021,

we employed 10 individuals, all of whom are full-time employees, of which 5 were part of our research and clinical development

team and 5 were part of our financial reporting and accounting team.

A significant number of our management and professional employees

have had prior experience with pharmaceutical, biotechnology or medical product companies.

None of our employees are covered by

collective bargaining agreements, and management considers relations with our employees to be in good standing.

Although we continually

seek to add additional talent to our work force, management believes that it has sufficient human capital to operate its business

successfully.

Competitive Pay and Benefits

Our compensation programs are designed

to align the compensation of our employees with our performance and to provide the proper incentives to attract, retain and motivate

employees to achieve superior results.

The structure of our compensation programs balances incentive earnings for both short-term

and long-term performance.

Specifically:

we provide employee wages that are competitive and

consistent with employee positions, skill levels, experience, knowledge and geographic location;

we engage nationally recognized outside compensation

and benefits consulting firms to independently evaluate the effectiveness of our executive compensation and benefit programs and

to provide benchmarking against our peers within the industry;

we align our executives’

long-term equity compensation

with our shareholders’

interests by linking realizable pay with stock performance;

all employees are eligible for health insurance, paid

and unpaid leaves, a retirement plan and life and disability/accident coverage.

We also offer a variety of voluntary benefits

that allow employees to select the options that meet their needs, including flexible time-off, telemedicine, and unpaid parental

Health and Safety

health and safety of our employees is our highest priority, and this is consistent with our operating philosophy.

w ith the global spread of the ongoing novel coronavirus pandemic, we have implemented plans designed to address and mitigate

the impact of the COVID-19 pandemic on the safety of our employees and our business, which include:

adding work from home flexibility;

adjusting attendance policies to encourage those who

are sick to stay home;

increasing cleaning protocols across all locations;

initiating regular communication regarding impacts of

the COVID-19 pandemic, including health and safety protocols and procedures.

Our principal executive offices are located

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by reference into, and does not form any part of, this Annual Report on Form 10-K.

We have included our website address as a factual

reference and do not intend it to be an active link to our website.

Our Annual Reports on Form 10-K, Quarterly Reports on Form

10-Q and Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the

Exchange Act are available free of charge through the investor relations page of our internet website as soon as reasonably practicable

after we electronically file such material with, or furnish it to, the SEC.

The following Corporate Governance documents are also

posted on our website:

Code of Conduct, Code of Ethics for Financial Management and the Charters for the Audit Committee, Compensation

Committee and Nominations Committee of the Board of Directors.

Our phone number is (301) 417-4364 and our facsimile number is (301)

We have included our website address as

a factual reference and do not intend it to be an active link to our website.

Our Annual Reports on Form 10-K, Quarterly Reports

on Form 10-Q and Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or

15(d) of the Exchange Act are available free of charge through the investor relations page of our internet website as

soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

The following Corporate

Governance documents are also posted on our website:

Code of Conduct, Code of Ethics for Financial Management and the Charters

for the Audit Committee, Compensation Committee and Nominations Committee of the Board of Directors.

Our phone number is (301)

417-4364 and our facsimile number is (301) 417-4367.

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