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Item 1. Business

2022-03-30 compared with 2021-03-16 · 564 added, 516 removed, 30 unchanged (97% of the section changed)

We are a clinical-stage biopharmaceutical company

and were formed in May 2017 to initially focus on developing new generation therapies for dermatological disorders.

that our pipeline has the potential to improve the quality of life for patients suffering from indications including atopic dermatitis

(also known as eczema), chronic wounds, psoriasis, asthma and acne.

Since our formation, we have expanded our business to

also focus on developing (i) a topical formulation for treating side effects from drugs used for the treatment of cancer;

a treatment for asthma and allergies using inhalational administration;

(iii) a topical treatment for patients with lupus;

a treatment for mast-cell derived cancers and anaphylaxis;

and (v) a treatment for lung diseases resulting from bacterial infections.

We are also focused on potentially developing a COVID-19 treatment as well as a diagnostic device for the detection of SARS-CoV-2

via a mobile device.

Dermatological Disorders

The BioLexa Platform

We have obtained an

exclusive license from the University of Cincinnati to make, use, have made, import, offer for sale, and sell products based upon

or involving the use of (i) topical compositions comprising a zinc chelator and gentamicin and (ii) zinc chelators to inhibit biofilm

formation (the “BioLexa Platform”

or “BioLexa”).

are a clinical-stage biopharmaceutical company focused on developing new generation therapies for unmet medical needs.

We are focused

on developing (i) a topical formulation for treating side effects from drugs used for the treatment of cancer;

(ii) a treatment for mast-cell

derived cancers and anaphylaxis;

and (iii) a treatment and/or prevention for Alzheimer’s or other neuroinflammatory diseases.

also have preclinical assets being developed for (i) atopic dermatitis (also known as eczema);

(ii) a treatment for asthma and allergies

using inhalational administration;

(iii) a treatment for lung diseases resulting from bacterial infections;

and (iv) a treatment for

inflammatory bowel diseases.

We are also developing a diagnostic device via a mobile device.

February 1, 2020, we entered into a patent license agreement with The George Washington University (“GW”) pursuant to which

GW granted us a license to certain patent rights to, among other things, make, use, offer and sell certain licensed products throughout

the world with respect to HT-001 which we intend to potentially use for treating dermatological side effects from epidermal growth factor

receptor (“EGFR”) inhibitors, and potentially other drugs used for the treatment of cancer.

HT-001 is a topical formulation

under development for the treatment of patients with rash and skin disorders associated with initial and repeat courses of tyrosine kinase

EGFR inhibitor therapy.

EGFR inhibitors are used for the treatment of cancers with EGFR up-regulation (such as non-small cell lung cancer,

pancreatic cancer, breast cancer and colon cancer);

however, EGFR inhibitors are often associated with dose-limiting skin toxicities

that can result in the interruption or reduction of treatment.

HT-001 is targeted to treat these EGFR-induced skin disorders to allow

patients to achieve the best potential outcomes of EGFR therapy.

HT-001 has achieved positive results in its initial pre-clinical studies

conducted at GW.

In December 2020, we submitted a pre-IND meeting request to the FDA with respect to HT-001 as a concomitant therapy

with EGFR inhibitors.

In preparation for such pre-IND meeting, we prepared and submitted to the FDA our IND-opening clinical trial plan

in January 2021, which includes two phase 2 trials conducted in patients.

Based on the FDA’s feedback, we intend to advance our

IND-enabling activities for HT-001 as planned.

We have engaged Worldwide Clinical Trials (“Worldwide”) as our clinical research

organization to provide clinical management, data management, biostatistical, medical monitoring, pharmacovigilance, and other related

services to support the CLEER1 Phase 2a clinical trial in the United States.

believe that the key elements for our market success with respect to HT-001 include:

our knowledge, there are currently no drugs approved for the treatment of skin toxicities associated with EFGR inhibitor therapy and

49-100% of patients develop skin toxicities during EGFR inhibitory therapy;

main active ingredient of HT-001 is already approved in oral and IV dosage forms which supports pursuit of the 505(b)(2) regulatory pathway

to reduce development time and cost;

our knowledge, there are no current topical formulations available using HT-001’s active ingredient so we believe that there is

no direct market competition;

have the potential to pursue other indications such as chronic pruritus, atopic dermatitis and other skin toxicities that develop from

anti-cancer therapies using the HT-001 formulation.

have obtained from North Carolina State University an exclusive, worldwide, royalty bearing license to certain intellectual property

to, among other things, discover, develop, make, have made, use and sell certain licensed products and sell, use and practice certain

licensed services with respect to cancer and anaphylaxis;

this is being developed as HT-KIT.

The HT-KIT drug is designed to more specifically

target the receptor tyrosine kinase KIT in mast cells, which is required for the proliferation, survival and differentiation of bone

marrow-derived hematopoietic stem cells.

Mutations in the KIT pathway have been associated with several human cancers, such as gastrointestinal

stromal tumors and mast cell-derived cancers (mast cell leukemia and mast cell sarcoma).

Based on the initial proof-of-concept success,

we intend to initially target mast cell neoplasms for development of HT-KIT, which is a rare, aggressive cancer with poor prognosis.

same target, KIT, also plays a key role in mast cell-mediated anaphylaxis, a serious allergic reaction that is rapid in onset and may

Anaphylaxis typically occurs after exposure to an external allergen that results in an immediate and severe immune response.

We also intend to pursue the anaphylaxis indication for HT-KIT in parallel to cancer treatment.

December 21, 2021, we submitted an Orphan Drug Designation (“ODD”) request to the U.S.

Food and Drug Administration (“FDA”)

for HT-KIT for the treatment of mastocytosis, and on March 10, 2022, we received ODD for HT-KIT for the treatment of mastocytosis.

intended to treat orphan diseases (rare diseases that affect less than 200,000 people in the U.S.) are eligible to apply for ODD, which

provides benefits such as 7 year marketing exclusivity and tax incentives to the sponsor during development and after approval.

February 23, 2021, we filed a provisional patent application with the United States Patent and Trademark Office for the use of the active

ingredient of HT-001 to treat and prevent Alzheimer’s disease and other neuroinflammatory diseases.

intend to develop HT-ALZ for use in patients following the Section 505(b)(2) regulatory pathway of the FDA rules.

Section 505(b)(2) of

the Federal Food, Drug, and Cosmetic Act (“FDCA”) was enacted to enable sponsors to seek New Drug Application (“NDA”)

approval for novel repurposed drugs without the need for such sponsors to undertake time consuming and expensive pre-clinical safety

studies and Phase 1 safety studies.

Proceeding under this regulatory pathway, we will be able to rely upon publicly available data

with respect to our active ingredient in our NDA submission to the FDA for marketing approval.

June 7, 2021, we entered into a sponsored research agreement with The Washington University to investigate the effects of HT-ALZ on behavioral

and pathological markers of Alzheimer’s disease and to determine if HT-ALZ can improve learning and memory in an animal model of

Alzheimer’s disease.

Our study will also determine if behavior is improved utilizing HT-ALZ in blocking NK-1Rs.

The study commenced

in August 2021 and we expect preclinical results in 2022.

BioLexa Platform

have obtained an exclusive license from the University of Cincinnati to make, use, have made, import, offer for sale, and sell products

based upon or involving the use of (i) topical compositions comprising a zinc chelator and gentamicin and (ii) zinc chelators to inhibit

biofilm formation (the “BioLexa Platform” or “BioLexa”).

The license enables us to develop the platform for any

2 unchanged sentences

is a proprietary, patented, drug compound platform for the treatment of eczema.

It combines an FDA-approved zinc chelator with

one or more approved antibiotics in a topical dosage form to address unchecked eczema flare-ups by preventing the formation of

infectious biofilms and the resulting clogging of sweat ducts.

We intend to initially use the BioLexa Platform to develop two different

topical cream products:

(i) a product to treat eczema and (ii) a product that reduces post-procedure infections, accelerates healing

and improves clinical outcomes for patients undergoing aesthetic dermatology procedures.

The technology is based on scientific research

into the mechanism of Staphylococcus biofilm formation conducted by Andrew B.

Herr, PhD at the University of Cincinnati.

conducted multiple in-vitro experiments, or experiments conducted in a controlled environment outside of a living organism, demonstrating

that chelation of zinc can prevent Staphylococcus bacteria from forming complex colonies called a biofilm.

used by bacteria as a defense mechanism against the host immune response and antibiotics.

Prevention of the biofilm formation leaves

the bacteria in their planktonic, or single cell state and susceptible to host immune defenses and antibiotic therapy.

in-vitro work demonstrating that zinc is an enabler for staph -biofilm formation led to the design and implementation

of a series of in-vivo experiments, or experiments conducted using living organisms.

These experiments were conducted at the University

of Miami using a minipig wound infection model and intended to demonstrate that the combination of zinc removal, or chelation,

and broad spectrum antibiotic therapy was more effective than either approach on its own.

These positive results supported development

of the BioLexa Platform for multiple indications with staph -biofilms as the causative agent.

We intend to develop

the BioLexa Platform for use in patients following the Section 505(b)(2) regulatory pathway of the U.S.

Food and Drug Administration (“FDA”)

Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (“FDCA”) was enacted to enable sponsors to

seek New Drug Application (“NDA”) approval for novel repurposed drugs without the need for such sponsors to undertake

time consuming and expensive pre-clinical safety studies and Phase 1 safety studies.

Proceeding under this regulatory pathway,

we will be able to rely upon publicly available data with respect to gentamicin and zinc chelator in our NDA submission to the

FDA for marketing approval.

In September 2018,

we attended the first of a series of meetings with the FDA to review the requirements for submission and activation of an investigational

new drug application (“IND”) with respect to the BioLexa Platform for use in eczema.

We prepared and presented to the

FDA our proposed first in human clinical trial plan for the treatment of eczema in patients over the age of one year old, and the

FDA provided us with general guidance with respect to specific animal studies, dosing schedules and suggested human safety studies

It combines an FDA approved zinc chelator with one or

more approved antibiotics in a topical dosage form to address unchecked eczema flare-ups by preventing the formation of infectious biofilms

and the resulting clogging of sweat ducts.

technology is based on scientific research into the mechanism of Staphylococcus biofilm formation conducted by Andrew B.

the University of Cincinnati.

Herr conducted multiple in-vitro experiments, or experiments conducted in a controlled environment

outside of a living organism, demonstrating that chelation of zinc can prevent Staphylococcus bacteria from forming complex

colonies called a biofilm.

Biofilms are used by bacteria as a defense mechanism against the host immune response and antibiotics.

of the biofilm formation leaves the bacteria in their planktonic, or single cell state and susceptible to host immune defenses and antibiotic

Herr’s in-vitro work demonstrating that zinc is an enabler for staph -biofilm formation led to the design

and implementation of a series of in-vivo experiments, or experiments conducted using living organisms.

These experiments were conducted

at the University of Miami using a minipig wound infection model and intended to demonstrate that the combination of zinc removal, or

chelation, and broad spectrum antibiotic therapy was more effective than either approach on its own.

These positive results supported

development of the BioLexa Platform for multiple indications with staph -biofilms as the causative agent.

intend to develop the BioLexa Platform for use in patients following the Section 505(b)(2) regulatory pathway of the FDA rules.

505(b)(2) of the Federal Food, Drug and Cosmetic Act (“FDCA”) was enacted to enable sponsors to seek New Drug Application

(“NDA”) approval for novel repurposed drugs without the need for such sponsors to undertake time consuming and expensive

pre-clinical safety studies and Phase 1 safety studies.

Proceeding under this regulatory pathway, we will be able to rely upon publicly

available data with respect to gentamicin and zinc chelator in our NDA submission to the FDA for marketing approval.

September 2018, we attended the first of a series of meetings with the FDA to review the requirements for submission and activation of

an investigational new drug application (“IND”) with respect to the BioLexa Platform for use in eczema.

We prepared and presented

to the FDA our proposed first in human clinical trial plan for the treatment of eczema in patients over the age of one year old, and

the FDA provided us with general guidance with respect to specific animal studies, dosing schedules and suggested human safety studies

before we commence clinical trials in pediatric or adult patients.

1 unchanged sentence

in adults prior to investigating pediatric and adolescent patients.

Therefore, we planned to conduct our first clinical trial for

BioLexa in Australia in order to enroll both adult and adolescents to support future clinical development.

On August 13, 2020,

we submitted our application for approval to conduct our clinical trial of BioLexa to the Belberry Human Research Ethics Committee

(“HREC”) in Australia and received approval from HREC on December 9, 2020.

We have engaged Novotech (Australia) Pty

Limited as our local clinical research organization in Australia to provide clinical management, data

management, biostatistical, medical monitoring, pharmacovigilance, and other related services to support the first in human clinical

trial of BioLexa.

We believe that the key elements for our market success with respect

to BioLexa include:

the proprietary formulation of two FDA-approved drugs to treat bacterial proliferation which may reduce development time and costs by giving us the ability to rely on safety and efficacy data from the two approved drugs;

our proprietary formulation is not a topical corticosteroid, and provides a novel mechanism of action and potentially a preferred safety profile as a market differentiator;

the recent literature set forth below reaffirms

the critical role that S.

aureus plays in the development of atopic dermatitis flare-ups within the international medical

community, supporting the targeted mechanism of action of BioLexa.

Shi et al, “MRSA Colonization

is Associated with Decreased Skin Commensal Bacteria in Atopic Dermatitis,”

Invest Dermatol.

Blicharz, et al, “Staphylococcus

an underestimated factor in the pathogenesis of atopic dermatitis?,”

Adv Dermatol Allergol 2019.

On February 1, 2020, we entered into a patent

license agreement with The George Washington University (“GW”) pursuant to which GW granted us a license to certain

patent rights to, among other things, make, use, offer and sell certain licensed products throughout the world with respect to

HT-001 which we intend to potentially use for treating dermatological side effects from epidermal growth factor receptor (“EGFR”)

inhibitors, and potentially other drugs used for the treatment of cancer.

HT-001 is a topical formulation under development for

the treatment of patients with rash and skin disorders associated with initial and repeat courses of tyrosine kinase EGFR inhibitor

EGFR inhibitors are used for the treatment of cancers with EGFR up-regulation (such as non-small cell lung cancer, pancreatic

cancer, breast cancer and colon cancer);

however, EGFR inhibitors are often associated with dose-limiting skin toxicities that

can result in the interruption or reduction of treatment.

HT-001 is targeted to treat these EGFR-induced skin disorders to allow

patients to achieve the best potential outcomes of EGFR therapy.

HT-001 has achieved positive results in its initial pre-clinical

studies conducted at GW.

In December 2020, we submitted a pre-IND meeting request to the FDA with respect to HT-001 as a concomitant

therapy with EGFR inhibitors.

In preparation for such pre-IND meeting, we prepared and submitted to the FDA our IND-opening clinical

trial plan in January 2021, which includes two phase 2 trials conducted in patients.

Based on the FDA’s feedback, we intend

to advance our IND-enabling activities for HT-001 as planned.

We believe that the key elements for our market success with respect

to HT-001 include:

To our knowledge, there are currently no drugs approved for the treatment of skin toxicities associated with EFGR inhibitor therapy and 49-100% of patients develop skin toxicities during EGFR inhibitory therapy;

The main active ingredient of HT-001 is already approved in oral and IV dosage forms which supports pursuit of the 505(b)(2) regulatory pathway to reduce development time and cost;

To our knowledge, there are no current topical formulations available using HT-001’s active ingredient so we believe that there is no direct market competition;

We have the potential to pursue other indications such as chronic pruritus, atopic dermatitis and other skin toxicities that develop from anti-cancer therapies using the HT-001 formulation.

On July 30, 2020 (the “Isoprene Effective

Date”), we entered into a Sublicense Agreement (the “Isoprene Sublicense Agreement”) with Isoprene Pharmaceuticals,

(“Isoprene”) pursuant to the commercial evaluation sublicense and option agreement dated March 8, 2019 by and

among us, the University of Maryland, Baltimore and Isoprene.

Pursuant to the Isoprene Sublicense Agreement, Isoprene granted us

an exclusive sublicense to certain intellectual property (i) to make, have made, use, sell, offer to sell and import certain licensed

products, (ii) in connection therewith, to use certain inventions and licensed materials and (iii) to practice certain patent rights

for the treatment of dermatological conditions or diseases, referred to as HT-003.

Retinoids, which include Vitamin A (retinol)

and its analogues (both synthetic and metabolites), play a critical role in cell signaling and biological processes, including

regulation of immune cells and inflammation, signaling pathways that control normal skin maintenance, embryonic development and

cell growth/differentiation/repair.

Deficiencies in retinoids and their active metabolites have been implicated in a wide variety

In the skin, retinol deficiency leads to hyperkeratosis and keratinizing metaplasia that is observed in skin disorders

like psoriasis and acne.

Therefore, we planned to conduct our first clinical trial for BioLexa

in Australia in order to enroll both adult and adolescents to support future clinical development.

December 9, 2020, we received approval from the Belberry Human Research Ethics Committee (“HREC”) in Australia to conduct

our clinical trial of BioLexa, and we have engaged Novotech (Australia) Pty Limited (“Novotech”) as our local clinical research

organization in Australia to provide clinical management, data management, biostatistical, medical monitoring, pharmacovigilance, and

other related services to support the first in human clinical trial of BioLexa.

Phase 1 of the trial was initiated in 2021 and is expected

to conclude in 2022.

believe that the key elements for our market success with respect to BioLexa include:

proprietary formulation of two FDA-approved drugs to treat bacterial proliferation which may reduce development time and costs

by giving us the ability to rely on safety and efficacy data from the two approved drugs;

proprietary formulation is not a topical corticosteroid, and provides a novel mechanism of action and potentially a preferred safety

profile as a market differentiator;

literature set forth below reaffirms the critical role that S.

aureus plays in the development of atopic dermatitis flare-ups

within the international medical community, supporting the targeted mechanism of action of BioLexa.

et al, “MRSA Colonization is Associated with Decreased Skin Commensal Bacteria in Atopic Dermatitis,” Invest Dermatol.

et al, “Staphylococcus aureus:

an underestimated factor in the pathogenesis of atopic dermatitis?,” Adv Dermatol Allergol

July 30, 2020 (the “Isoprene Effective Date”), we entered into a Sublicense Agreement (the “Isoprene Sublicense Agreement”)

with Isoprene Pharmaceuticals, Inc.

(“Isoprene”) pursuant to the commercial evaluation sublicense and option agreement dated

March 8, 2019 by and among us, the University of Maryland, Baltimore and Isoprene.

Pursuant to the Isoprene Sublicense Agreement, Isoprene

granted us an exclusive sublicense to certain intellectual property (i) to make, have made, use, sell, offer to sell and import certain

licensed products, (ii) in connection therewith, to use certain inventions and licensed materials and (iii) to practice certain patent

rights for the treatment of dermatological conditions or diseases, referred to as HT-003.

The retinoic acid metabolism blocking agents

(“RAMBAs”) have the potential to be developed as a platform for multiple inflammatory-based indications.

Accordingly, we

entered into a Sublicense Agreement with Isoprene on July 2, 2021 pursuant to the option agreement dated December 22, 2020 to expand

the therapeutic indication of the sublicensed RAMBAs from Isoprene to include inflammatory bowel diseases, including Crohn’s disease

and ulcerative colitis.

which include Vitamin A (retinol) and its analogues (both synthetic and metabolites), play a critical role in cell signaling and biological

processes, including regulation of immune cells and inflammation, signaling pathways that control normal skin maintenance, embryonic

development and cell growth/differentiation/repair.

Deficiencies in retinoids and their active metabolites have been implicated in a

wide variety of diseases.

In the skin, retinol deficiency leads to hyperkeratosis and keratinizing metaplasia that is observed in skin

disorders like psoriasis and acne.

Vitamin A and retinoic acid also play a crucial role in regulating cell proliferation, differentiation,

and apoptosis and therefore, altered metabolism of retinoids has been suspected as playing a potential role in tumorigenesis.

retinoids have been approved in the US for treatment of acne and psoriasis as well as other therapeutic indications such as acute

promyelocytic leukemia and cutaneous T-cell lymphoma;

however, the therapeutic use of exogenous retinoids has been limited due

to negative effects associated with high systemic concentrations.

A new therapeutic approach to increase intracellular retinoic

acid (the active metabolite of retinol) potentially without causing negative side effects of exogenous retinoic acid is to use

inhibitors of retinoic acid metabolism (collectively, “RAMBAs”), which prolong the presence of retinoic acid.

is a novel RAMBA under investigation for topical treatment in acne and psoriasis applications.

In December 2019, we entered into a research

collaboration agreement with Weill Cornell Medicine for the completion of pre-clinical studies investigating the mechanism of action

of HT-003 that was renewed in January 2021 as a result of positive preclinical results.

Jonathan Zippin, M.D., Ph.D., FAAD,

Associate Professor of Dermatology at Weill Cornell Medicine and our Senior Scientific Advisor, is the principal investigator for

such pre-clinical studies.

The RAMBAs have the potential to be developed

as a platform for multiple inflammatory-based indications.

Accordingly, on December 22, 2020, we entered into an option agreement

to expand the therapeutic indication of the sublicensed RAMBAs from Isoprene.

The option agreement includes the investigation of

RAMBAs for treatment of inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis.

Preclinical proof-of-concept

studies began in the first quarter of 2021.

HT-005 Z-Pods™

On August 19, 2019, we entered into a sublicense

agreement with Zylö

Therapeutics, Inc.

(“Zylö”) pursuant to which Zylö

granted us an exclusive

sublicense to certain licensed patent rights and certain licensed technology to, among other things, develop, make and sell certain

licensed products and to practice certain licensed technology in the United States and Canada initially with respect to therapeutic

uses related to lupus in humans.

HT-005 Z-Pods™

include a novel topical delivery matrix (Z-Pods™) loaded with an endogenous

ligand with suspected immune-modulating action.

Z-Pods™

use patented xerogel-derived nanoparticles for sustained and controlled

topical delivery of active pharmaceutical ingredients.

In 2020, Zylö

completed positive proof of concept data in a lupus mouse

model to support further development activities in 2021.

Genetic Marker for Food Allergies

On May 18, 2018, we entered into an exclusive

license agreement with the University of Cincinnati for a patented, novel genetic marker for food allergies.

The genetic marker

licensed may be used to (i) identify at risk infants in predicting food allergies, including peanut and milk allergies, (ii) identify

a person’s predisposition to an allergic reaction and (iii) determine an individual’s propensity to develop atopic

dermatitis, such as eczema.

We intend to utilize the genetic marker in the future for purposes of determining an individual’s

propensity to develop eczema as well as to identify and treat allergies in at-risk infants.

Respiratory Products

On November 20, 2019, we entered into a license

agreement with North Carolina State University (“NC State”) pursuant to which NC State granted us an exclusive license

to, among other things, develop, make, use, offer and sell certain licensed products throughout the world with respect to HT-004

for treating allergic diseases.

HT-004 is a potential disease-modifying agent that uses exon-skipping oligonucleotide-targeted

methods to reduce mast cell responses to immunoglobulin E (IgE)-directed antigens, which is one of the key mechanisms in the pathophysiology

of asthma, atopic dermatitis and other allergic diseases.

HT-004 is currently under investigation for the treatment of asthma and

allergies using inhalational administration.

Preclinical proof-of-concept data was generated

in October 2020 supporting efficacy of HT-004 after inhalational delivery in a mouse model.

Critical proof-of-concept studies in

a humanized mouse model are planned to be conducted in 2021.

These studies are being conducted by our Scientific Advisory Board

retinoids have been approved in the U.S.

for treatment of acne and psoriasis as well as other therapeutic indications such as acute promyelocytic

leukemia and cutaneous T-cell lymphoma;

however, the therapeutic use of exogenous retinoids has been limited due to negative effects

associated with high systemic concentrations.

A new therapeutic approach to increase intracellular retinoic acid (the active metabolite

of retinol) potentially without causing negative side effects of exogenous retinoic acid is to use inhibitors of RAMBAs, which prolong

the presence of retinoic acid.

HT-003 is a novel RAMBA under investigation for topical treatment in acne and psoriasis applications.

December 2019, we entered into a research collaboration agreement with Weill Cornell Medicine for the completion of pre-clinical studies

investigating the mechanism of action of HT-003 that was renewed in January 2021 as a result of positive preclinical results.

Zippin, M.D., Ph.D., FAAD, Associate Professor of Dermatology at Weill Cornell Medicine and our Senior Scientific Advisor, is the principal

investigator for such pre-clinical studies.

proof-of-concept studies began in the first quarter of 2021 for the investigation of RAMBAs for treatment of inflammatory bowel diseases,

including Crohn’s disease and ulcerative colitis.

November 20, 2019, we entered into a license agreement with North Carolina State University (“NC State”) pursuant to which

NC State granted us an exclusive license to, among other things, develop, make, use, offer and sell certain licensed products throughout

the world with respect to HT-004 for treating allergic diseases.

HT-004 is a potential disease-modifying agent that uses exon-skipping

oligonucleotide-targeted methods to reduce mast cell responses to immunoglobulin E (IgE)-directed antigens, which is one of the key mechanisms

in the pathophysiology of asthma, atopic dermatitis and other allergic diseases.

HT-004 is currently under investigation for the treatment

of asthma and allergies using inhalational administration.

proof-of-concept data was generated in October 2020 supporting efficacy of HT-004 after inhalational delivery in a mouse model.

proof-of-concept studies in a humanized mouse model are planned to be conducted in 2022.

These studies are being conducted by our Scientific

Advisory Board member, Dr.

Glenn Cruse, at NC State.

We believe that the key elements for our market

success with respect to HT-004 include:

To our knowledge, there are currently no disease-modifying agents for asthma or allergy diseases;

The active pharmaceutical ingredient in HT-004 is a novel molecular class that we believe would prevent generic competition after commercialization;

HT-004 is being developed for inhalational administration by either inhaler or nebulizer for easy access at home by patients;

HT-004 is applicable for both adult and pediatric patient populations with asthma and/or allergies.

On December 22, 2020, we entered into a non-exclusive

commercial evaluation license agreement with the U.S.

Army Medical Research and Development Command (“USAMRDC”), as

amended, pursuant to which USAMRDC granted us a non-exclusive commercial evaluation license to HT-006 for the treatment of lung

diseases resulting from bacterial infections.

We will initially target treatment of serious bacterial infections of the lung, such

as hospital-acquired pneumonia (“HAP”) and ventilator-associated pneumonia (“VAP”).

Given the indication,

we intend to develop HT-006 for inhalational administration.

Both HAP and VAP are considered life-threatening

diseases for which current treatment options are limited or not effective against multi-drug resistance bacteria.

As such, we intend

to pursue streamlined development opportunities under the FDA’s program for “antibacterial therapies for patients with

an unmet medical need for the treatment of serious bacterial diseases.”

This streamlined program allows for the use of nonclinical

animal studies to reduce clinical studies required for approval.

We intend to begin proof-of-concept preclinical

testing in the first quarter of 2021.

Cancer Treatments

We have obtained from NC State an exclusive,

worldwide, royalty bearing license to certain intellectual property to, among other things, discover, develop, make, have made,

use and sell certain licensed products and sell, use and practice certain licensed services with respect to cancer and anaphylaxis;

this is being developed as HT-KIT.

The HT-KIT drug is designed to more specifically target the receptor tyrosine kinase KIT in

mast cells, which is required for the proliferation, survival and differentiation of bone marrow-derived hematopoietic stem cells.

Mutations in the KIT pathway have been associated with several human cancers, such as gastrointestinal stromal tumors and mast

cell-derived cancers (mast cell leukemia and mast cell sarcoma).

Based on the initial proof-of-concept success, we intend to initially

target mast cell neoplasms for development of HT-KIT, which is a rare, aggressive cancer with poor prognosis.

The same target, KIT, also plays a key role

in mast cell-mediated anaphylaxis, a serious allergic reaction that is rapid in onset and may cause death.

Anaphylaxis typically

occurs after exposure to an external allergen that results in an immediate and severe immune response.

We also intend to pursue

the anaphylaxis indication for HT-KIT in parallel to cancer treatment.

COVID-19 Products

On May 18, 2020, we entered into an Exclusive

License Agreement with the Virginia Commonwealth University Intellectual Property Foundation (“VCU”) pursuant to which

VCU granted us an exclusive, royalty bearing license to HT-002, a novel peptide developed by researchers at VCU that

may be used to slow the transmission of SARS-CoV-2 (the “VCU Peptide”) and a non-exclusive royalty bearing,

worldwide license with respect to certain licensed technical information patents to make, have made, use, offer to sell, sell and

import certain licensed products and perform certain licensed services.

On June 29, 2020, we entered into a Sponsored Project Agreement

with VCU for the development of a potential COVID-19 treatment using the VCU Peptide.

Proof-of-Concept preclinical studies are expected

to be completed in 2021.

VaxCelerate SARS-CoV-2 Vaccine

On March 23, 2020, we entered into a Royalty

and Development Agreement (the “Voltron Agreement”) with Voltron Therapeutics, Inc.

(“Voltron”), pursuant

to which we formed a joint venture entity named HaloVax, LLC (“HaloVax”), to jointly develop potential product candidates

for the prevention of COVID-19 based upon certain technology that had been exclusively licensed by Voltron from The General Hospital

Corporation (d/b/a Massachusetts General Hospital) (“Mass Gen”).

The SARS-CoV-2 vaccine is being developed using VaxCelerate,

a self-assembling vaccine platform licensed from Mass Gen by HaloVax.

VaxCelerate offers two unique elements to combat SARS-CoV-2:

a fixed immune adjuvant and variable immune targeting, the combination which is designed to illicit a robust, protective immune

Critical IND-enabling preclinical studies are

planned to be completed in 2021.

On-the-Go Sars-Cov-2 Testing Device

On August 7, 2020, we entered into a patent

license agreement (the “GW Patent License Agreement”) with GW pursuant to which GW granted us an exclusive, worldwide,

royalty bearing license to certain intellectual property that can be used to develop a device designed to detect the presence of

Specifically, the GW Patent License Agreement permits us to make, have made, use, import, offer for sale and sell certain

licensed products in the field of virus sensing and detection.

On September 17, 2020, we entered into a sponsored research agreement

with GW relating to the development of a diagnostic device for the detection of SARS-CoV-2 via a mobile device as an aid in the

diagnosis of the COVID-19 infection.

Product Development Pipeline

The following table summarizes our product

believe that the key elements for our market success with respect to HT-004 include:

our knowledge, there are currently no disease-modifying agents for asthma or allergy diseases;

active pharmaceutical ingredient in HT-004 is a novel molecular class that we believe would prevent generic competition after commercialization;

is being developed for inhalational administration by either inhaler or nebulizer for easy access at home by patients;

is applicable for both adult and pediatric patient populations with asthma and/or allergies.

December 22, 2020, we entered into a non-exclusive commercial evaluation license agreement with the U.S.

Army Medical Research and Development

Command (“USAMRDC”), as amended, pursuant to which USAMRDC granted us a non-exclusive commercial evaluation license to HT-006

for the treatment of lung diseases resulting from bacterial infections.

We will initially target treatment of serious bacterial infections

of the lung, such as hospital-acquired pneumonia (“HAP”) and ventilator-associated pneumonia (“VAP”).

indication, we intend to develop HT-006 for inhalational administration.

HAP and VAP are considered life-threatening diseases for which current treatment options are limited or not effective against multi-drug

resistance bacteria.

As such, we intend to pursue streamlined development opportunities under the FDA’s program for “antibacterial

therapies for patients with an unmet medical need for the treatment of serious bacterial diseases.” This streamlined program allows

for the use of nonclinical animal studies to reduce clinical studies required for approval.

May 18, 2020, we entered into an Exclusive License Agreement with the Virginia Commonwealth University Intellectual Property Foundation

(“VCU”) pursuant to which VCU granted us an exclusive, royalty bearing license to HT-002, a novel peptide developed

by researchers at VCU that may be used to slow the transmission of SARS-CoV-2 (the “VCU Peptide”) and a non-exclusive

royalty bearing, worldwide license with respect to certain licensed technical information patents to make, have made, use, offer to sell,

sell and import certain licensed products and perform certain licensed services.

On June 29, 2020, we entered into a Sponsored Project

Agreement (“VCU SPA”) with VCU for the development of a potential COVID-19 treatment using the VCU Peptide.

The VCU SPA was

amended on April 28, 2021 to extend the period of research and to add additional scope of investigation to include the variants of SARS-CoV-2.

Proof-of-Concept

preclinical studies are expected to be completed in 2022.

Detect Breath Diagnostic Device

August 7, 2020, we entered into a Patent License Agreement (“GW Patent License Agreement”) with GW pursuant to which GW granted

us an exclusive, worldwide, royalty bearing license to certain intellectual property that can be used to develop a device designed to

detect the presence of viruses.

Specifically, the GW Patent License Agreement permits us to make, have made, use, import, offer for sale

and sell certain licensed products in the field of virus sensing and detection.

We have engaged a company to develop a platform prototype

and, once developed, we will select target analytes for further development.

Development Pipeline

The biopharmaceutical industry utilizes rapidly

advancing technologies and is characterized by intense competition.

There is also a strong emphasis on intellectual property and

proprietary products.

In the segment of the biopharmaceutical industry, competition from different sources including major biopharmaceutical

companies, academic institutions, government agencies, and public and private research institutions will continue.

competitors have significantly greater financial resources and expertise in product candidate development and may have progressed

further toward approval and marketing.

In addition, smaller or early-stage companies may also prove to be significant competitors,

particularly through collaborative arrangements with large and established companies.

Manufacturing and Supply

We do not have any manufacturing capability

and therefore we currently rely on and intend to continue to rely on contract manufacturing organizations to produce our product

candidates in accordance with regulatory requirements.

following table summarizes our product development pipeline.

We have interests in certain other assets being

developed by third parties.

Specifically, in December 2021, we entered into a license agreement

with Zylö Therapeutics, Inc.

(“Zylö”) with respect to the development of HT-005 .

We had previously entered into a sublicense agreement with Zylö pursuant to which we had advanced the development of HT-005

for patients with lupus.

(See Note 6 to the consolidated financial statements for a discussion of our agreement with Zylö).

In addition, in March 2020, we entered into a Royalty and Development Agreement (the “Voltron Agreement”) with Voltron

Therapeutics, Inc.

with respect to the development of potential product candidates for the prevention of COVID-19.

(See Note 6 to the

consolidated financial statements for a discussion of our agreement with Voltron).

biopharmaceutical industry utilizes rapidly advancing technologies and is characterized by intense competition.

There is also a strong

emphasis on intellectual property and proprietary products.

In the segment of the biopharmaceutical industry, competition from different

sources including major biopharmaceutical companies, academic institutions, government agencies, and public and private research institutions

will continue.

Many of our competitors have significantly greater financial resources and expertise in product candidate development

and may have progressed further toward approval and marketing.

In addition, smaller or early-stage companies may also prove to be significant

competitors, particularly through collaborative arrangements with large and established companies.

Manufacturing

do not have any manufacturing capability and therefore we currently rely on and intend to continue to rely on contract manufacturing

organizations to produce our product candidates in accordance with regulatory requirements.

Commercialization

Our success depends not only on the successful

development and approval of our products candidates but also on the commercialization of our potential products.

If and when our

product candidates receive regulatory approval, we intend to engage third-parties such as pharmaceutical and biotechnology companies

for the commercialization of our products.

Intellectual Property Portfolio

Our goal is to obtain, maintain and enforce

patent protection for our products, formulations, processes, methods and other proprietary technologies, preserve our trade secrets,

and operate without infringing on the proprietary rights of other parties, both in the U.S.

and in other countries.

is to actively seek the broadest intellectual property protection possible for our products, proprietary information and proprietary

technology through a combination of contractual arrangements and patents, both in the U.S.

success depends not only on the successful development and approval of our products candidates but also on the commercialization of our

potential products.

If and when our product candidates receive regulatory approval, we intend to engage third-parties such as pharmaceutical

and biotechnology companies for the commercialization of our products.

Property Portfolio

goal is to obtain, maintain and enforce patent protection for our products, formulations, processes, methods and other proprietary technologies,

preserve our trade secrets, and operate without infringing on the proprietary rights of other parties, both in the U.S.

Our policy is to actively seek the broadest intellectual property protection possible for our products, proprietary information

and proprietary technology through a combination of contractual arrangements and patents, both in the U.S.

and elsewhere in the world.

we intend to actively pursue product life-cycle management initiatives to extend our market exclusivity.

We intend to cement our market exclusivity

in conjunction with our formulation-development partners through additional patents based on the pharmaceutical and clinical characteristics

of our product candidates in the proprietary formulation and through the introduction of line extensions such as combination drugs

and new formulations.

In addition to any granted patents, our products

may be eligible for market exclusivity to run concurrently with the term of the patent for three and a half years in the U.S.

to the Hatch-Waxman Act and pediatric exclusivity guideline and up to ten years of market exclusivity in the E.U.

which includes

eight years of data exclusivity and two years of market exclusivity from the date we file an NDA or the European equivalent referred

to as Marketing Authorization Application.

Government Regulations

Governmental authorities in the U.S.

countries extensively regulate the research, development, testing, manufacture, labeling, promotion, advertising, distribution

and marketing of pharmaceutical products, including biological products, and medical devices, such as those being developed by

In the U.S., the FDA regulates such products under the FDCA and the Public Health Services Act and implements related regulations.

Failure to comply with applicable FDA requirements, both before and after approval, may subject us to administrative and judicial

sanctions, such as a delay in approving or refusal by the FDA to approve pending applications, warning letters, product recalls,

product seizures, total or partial suspension of production or distribution, injunctions and/or criminal prosecution.

In addition, we intend to actively pursue product life-cycle management initiatives to extend our market exclusivity.

intend to cement our market exclusivity in conjunction with our formulation-development partners through additional patents based on

the pharmaceutical and clinical characteristics of our product candidates in the proprietary formulation and through the introduction

of line extensions such as combination drugs and new formulations.

addition to any granted patents, our products may be eligible for market exclusivity to run concurrently with the term of the patent

for three and a half years in the U.S.

pursuant to the Hatch-Waxman Act and pediatric exclusivity guideline and up to ten years of market

exclusivity in the E.U.

which includes eight years of data exclusivity and two years of market exclusivity from the date we file an NDA

or the European equivalent referred to as Marketing Authorization Application.

We currently have

licenses to six U.S.

patents and one pending U.S.

patent application, and we have licenses to three patents issued in Europe and

Australia and five pending patent applications in foreign jurisdictions including Europe, Brazil, Canada and Hong Kong.

holds two pending U.S.

patent applications and one pending PCT patent application.

addition to patents, we rely on trade secrets and know-how and continuing technological innovation to develop and maintain our competitive

However, trade secrets and know-how can be difficult to protect.

We take measures to protect and maintain the confidentiality

of proprietary information in order to protect aspects of the business that are not amenable to, or that we do not consider appropriate

for, patent protection.

We require employees, consultants, outside scientific partners, sponsored researchers and other advisors to execute

confidentiality agreements with us on or prior to the commencement of employment or consulting relationships with us.

authorities in the U.S.

and other countries extensively regulate the research, development, testing, manufacture, labeling, promotion,

advertising, distribution and marketing of pharmaceutical products, including biological products, and medical devices, such as those

being developed by us.

In the U.S., the FDA regulates such products under the FDCA and the Public Health Services Act and implements

related regulations.

Failure to comply with applicable FDA requirements, both before and after approval, may subject us to administrative

and judicial sanctions, such as a delay in approving or refusal by the FDA to approve pending applications, warning letters, product

recalls, product seizures, total or partial suspension of production or distribution, injunctions and/or criminal prosecution.

Food and Drug Administration Regulations

United States Drug Development

In the United States, the FDA regulates drugs

(including biological products, such as vaccines), medical devices and combinations of drugs and devices, or combination products,

under the FDCA and its implementing regulations.

These products are also subject to other federal, state and local statutes and

The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local

and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

Failure to comply with

the applicable U.S.

requirements at any time during the product development process, approval process or after approval, may subject

an applicant to administrative or judicial sanctions.

These sanctions could include, among other actions, the FDA’s refusal

to approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters, requests for voluntary

States Drug Development

the United States, the FDA regulates drugs (including biological products, such as vaccines), medical devices and combinations of drugs

and devices, or combination products, under the FDCA and its implementing regulations.

These products are also subject to other federal,

state and local statutes and regulations.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate

federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.

to comply with the applicable U.S.

requirements at any time during the product development process, approval process or after approval,

may subject an applicant to administrative or judicial sanctions.

These sanctions could include, among other actions, the FDA’s

refusal to approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters, requests for voluntary

product recalls or withdrawals from the market, product seizures, total or partial suspension of production or distribution injunctions,

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action could have a material adverse effect on us.

The process required by the FDA before a drug

may be marketed in the United States generally involves the following:

completion of extensive pre-clinical laboratory tests, animal studies and formulation studies in accordance with applicable regulations, including the FDA’s Good Laboratory Practice regulations;

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

performance of adequate and well-controlled human clinical trials in accordance with an applicable IND and other clinical study related regulations, sometimes referred to as good clinical practices (“GCPs”) to establish the safety and efficacy of the proposed drug for its proposed indication;

submission to the FDA of an NDA or biologics license application (“BLA”);

satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with the FDA’s current good manufacturing practice (“cGMP”) requirements;

potential FDA audit of the clinical trial sites that generated the data in support of the NDA or BLA;

FDA review and approval of the NDA or BLA prior to any commercial marketing or sale.

Human clinical trials are typically conducted

in three sequential phases that may overlap or be combined:

The product is initially introduced into a small number of healthy human subjects or patients and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion and, if possible, to gain early evidence on effectiveness.

In the case of some products for severe or life-threatening diseases, especially when the product is suspected or known to be unavoidably toxic, the initial human testing may be conducted in patients.

Involves clinical trials in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage and schedule.

Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically dispersed clinical trial sites.

These clinical trials are intended to establish the overall risk/benefit relationship of the product and provide an adequate basis for product labeling.

Post-approval trials, sometimes referred to

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

These studies are used to gain additional experience

from the treatment of patients in the intended therapeutic indication.

In certain instances, the FDA may mandate the performance

of Phase 4 trials.

Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period,

process required by the FDA before a drug may be marketed in the United States generally involves the following:

of extensive pre-clinical laboratory tests, animal studies and formulation studies in accordance with applicable regulations, including

the FDA’s Good Laboratory Practice regulations;

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

performance of adequate and well-controlled human clinical trials in accordance with an applicable IND and other clinical study related regulations, referred to as good clinical practice (“GCP”), to establish the safety and efficacy of the proposed drug for its proposed indication;

to the FDA of an NDA or biologics license application (“BLA”);

● satisfactory

completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the product, or components thereof,

are produced to assess compliance with the FDA’s current good manufacturing practice (“cGMP”) requirements;

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

review and approval of the NDA or BLA prior to any commercial marketing or sale.

clinical trials are typically conducted in three sequential phases that may overlap or be combined:

The product is initially introduced into a small number of healthy human subjects or patients and tested for safety, dosage tolerance,

absorption, metabolism, distribution and excretion and, if possible, to gain early evidence on effectiveness.

In the case of some products

for severe or life-threatening diseases, especially when the product is suspected or known to be unavoidably toxic, the initial human

testing may be conducted in patients.

Involves clinical trials in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate

the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage and schedule.

Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population at geographically

dispersed clinical trial sites.

These clinical trials are intended to establish the overall risk/benefit relationship of the product

and provide an adequate basis for product labeling.

Post-approval

trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval.

These studies are used to

gain additional experience from the treatment of patients in the intended therapeutic indication.

In certain instances, the FDA may mandate

the performance of Phase 4 trials.

Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified

period, if at all.

The FDA or the clinical trial sponsor may suspend or terminate a clinical trial at any time on various grounds, including

a finding that the research subjects or patients are being exposed to an unacceptable health risk.

Similarly, an Institutional

Review Board (“IRB”), which oversees the conduct of clinical trials, can suspend or terminate approval of a clinical

trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the

product has been associated with unexpected serious harm to patients.

Additionally, some clinical trials are overseen by an independent

group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee.

group provides authorization for whether a trial may move forward at designated check points based on access to certain data from

The clinical trial sponsor may also suspend or terminate a clinical trial based on evolving business objectives and/or

competitive climate.

FDA Review Process

The results of product development, pre-clinical

studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the drug, proposed

labeling and other relevant information, are submitted to the FDA as part of an NDA for a new drug, or BLA for a biological product,

requesting approval to market the product.

The submission of an NDA or BLA is subject to the payment of a substantial user fee,

and the sponsor of an approved NDA or BLA is also subject to an annual program user fee;

although a waiver of such fee may be obtained

under certain limited circumstances.

The FDA reviews all NDAs submitted before it

accepts them for filing and may request additional information rather than accepting an NDA for filing.

Under the goals and policies

agreed to by the FDA under the Prescription Drug User Fee Act (“PDUFA”), the FDA’s goal to complete its substantive

review of a standard NDA and respond to the applicant is ten months from the receipt of the NDA.

The FDA does not always meet its

PDUFA goal dates, and the review process is often significantly extended by FDA requests for additional information or clarification

and may go through multiple review cycles.

The review and evaluation of an NDA or BLA

by the FDA is extensive and time consuming and may take longer than originally planned to complete, and we may not receive a timely

approval, if at all.

Before approving an NDA, the FDA will conduct

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

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

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

In addition, before approving

an NDA, the FDA may also audit data from clinical trials to ensure compliance with GCP requirements.

There is no assurance that the FDA will ultimately

approve a product for marketing in the United States, and we may encounter significant difficulties or costs during the review

If a product receives marketing approval, the approval may be significantly limited to specific diseases and dosages or

the indications for use may otherwise be limited, which could restrict the commercial value of the product.

Further, the FDA may

require that certain contraindications, warnings or precautions be included in the product labeling or may condition the approval

of the NDA or BLA on other changes to the proposed labeling, development of adequate controls and specifications, or a commitment

to conduct post-market testing or clinical trials and surveillance to monitor the effects of approved products.

For example, the

FDA may require Phase 4 clinical trials to further assess drug safety and effectiveness and may require testing and surveillance

programs to monitor the safety of approved products that have been commercialized.

The FDA may also place other conditions on approvals,

including the requirement for a risk evaluation and mitigation strategy (“REMS”), to assure the safe use of the drug.

Section 505(b)(2) Regulatory Approval

Section 505(b)(2) of the FDCA provides an alternate

regulatory pathway for approval of a new drug by allowing the FDA to rely on data not developed by the applicant.

Specifically,

Section 505(b)(2) permits the submission of an NDA where one or more of the investigations relied upon by the applicant for approval

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

The applicant may

rely upon published literature and/or the FDA’s findings of safety and effectiveness for an approved drug already on the

Approval or submission of a 505(b)(2) application, like those for abbreviated new drugs (“ANDAs”), may be delayed

because of patent and/or exclusivity rights that apply to the previously approved drug.

A 505(b)(2) application may be submitted for

a new chemical entity (“NCE”) when some part of the data necessary for approval is derived from studies not conducted

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

Section 505(b)(2) applications also may be

entitled to marketing exclusivity if supported by appropriate data and information.

Three-year new data exclusivity may be granted

to the 505(b)(2) application if one or more clinical investigations conducted in support of the application, other than bioavailability/bioequivalence

studies, were essential to the approval and conducted or sponsored by the applicant.

Five years of marketing exclusivity may be

granted if the application is for an NCE, and pediatric exclusivity is likewise available.

Orange Book Listing and Paragraph IV Certification

For NDA submissions, including those under

Section 505(b)(2), applicants are required to list with the FDA certain patents with claims that cover the applicant’s product.

Upon approval, each of the patents listed in the application is published in Approved Drug Products with Therapeutic Equivalence

Evaluations , commonly referred to as the Orange Book.

Any applicant who subsequently files an ANDA or 505(b)(2) NDA that references

a drug listed in the Orange Book must certify to the FDA that (1) no patent information on the drug product that is the subject

of the application has been submitted to the FDA;

Similarly, an Institutional Review

Board (“IRB”), which oversees the conduct of clinical trials, can suspend or terminate approval of a clinical trial at its

institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the product has been associated

with unexpected serious harm to patients.

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

organized by the clinical trial sponsor, known as a data safety monitoring board or committee.

This group provides authorization for

whether a trial may move forward at designated check points based on access to certain data from the study.

The clinical trial sponsor

may also suspend or terminate a clinical trial based on evolving business objectives and/or competitive climate.

Review Process

results of product development, pre-clinical studies and clinical trials, along with descriptions of the manufacturing process, analytical

tests conducted on the drug, proposed labeling and other relevant information, are submitted to the FDA as part of an NDA for a new drug,

or BLA for a biological product, requesting approval to market the product.

The submission of an NDA or BLA is subject to the payment

of a substantial user fee, and the sponsor of an approved NDA or BLA is also subject to an annual program user fee;

although a waiver

of such fee may be obtained under certain limited circumstances.

FDA reviews all NDAs submitted before it accepts them for filing and may request additional information rather than accepting an NDA

Under the goals and policies agreed to by the FDA under the Prescription Drug User Fee Act (“PDUFA”), the FDA’s

goal to complete its substantive review of a standard NDA and respond to the applicant is ten months from the receipt of the NDA.

FDA does not always meet its PDUFA goal dates, and the review process is often significantly extended by FDA requests for additional

information or clarification and may go through multiple review cycles.

review and evaluation of an NDA or BLA by the FDA is extensive and time consuming and may take longer than originally planned to complete,

and we may not receive a timely approval, if at all.

approving an NDA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine whether

they comply with cGMPs.

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

in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

before approving an NDA, the FDA may also audit data from clinical trials to ensure compliance with GCP requirements.

is no assurance that the FDA will ultimately approve a product for marketing in the United States, and we may encounter significant difficulties

or costs during the review process.

If a product receives marketing approval, the approval may be significantly limited to specific diseases

and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product.

FDA may require that certain contraindications, warnings or precautions be included in the product labeling or may condition the approval

of the NDA or BLA on other changes to the proposed labeling, development of adequate controls and specifications, or a commitment to

conduct post-market testing or clinical trials and surveillance to monitor the effects of approved products.

For example, the FDA may

require Phase 4 clinical trials to further assess drug safety and effectiveness and may require testing and surveillance programs to

monitor the safety of approved products that have been commercialized.

The FDA may also place other conditions on approvals, including

the requirement for a risk evaluation and mitigation strategy (“REMS”), to assure the safe use of the drug.

505(b)(2) Regulatory Approval Pathway

505(b)(2) of the FDCA provides an alternate regulatory pathway for approval of a new drug by allowing the FDA to rely on data not developed

by the applicant.

Specifically, Section 505(b)(2) permits the submission of an NDA where one or more of the investigations relied upon

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

The applicant may rely upon published literature and/or the FDA’s findings of safety and effectiveness for an approved drug already

on the market.

Approval or submission of a 505(b)(2) application, like those for abbreviated new drugs (“ANDAs”), may be

delayed because of patent and/or exclusivity rights that apply to the previously approved drug.

505(b)(2) application may be submitted for a new chemical entity (“NCE”) when some part of the data necessary for approval

is derived from studies not conducted by or for the applicant and when the applicant has not obtained a right of reference.

505(b)(2) applications also may be entitled to marketing exclusivity if supported by appropriate data and information.

Three-year new

data exclusivity may be granted to the 505(b)(2) application if one or more clinical investigations conducted in support of the application,

other than bioavailability/bioequivalence studies, were essential to the approval and conducted or sponsored by the applicant.

of marketing exclusivity may be granted if the application is for an NCE, and pediatric exclusivity is likewise available.

Book Listing and Paragraph IV Certification

NDA submissions, including those under Section 505(b)(2), applicants are required to list with the FDA certain patents with claims that

cover the applicant’s product.

Upon approval, each of the patents listed in the application is published in Approved Drug Products

with Therapeutic Equivalence Evaluations , commonly referred to as the Orange Book.

Any applicant who subsequently files an ANDA or

505(b)(2) NDA that references a drug listed in the Orange Book must certify to the FDA that (1) no patent information on the drug product

that is the subject of the application has been submitted to the FDA;

(2) such patent has expired;

(3) the date on which such patent expires;

such patent is invalid or will not be infringed upon by the manufacture, use or sale of the drug product for which the application

is submitted.

(3) the date on which such patent

or (4) such patent is invalid or will not be infringed upon by the manufacture, use or sale of the drug product for which the

application is submitted.

This last certification is known as a Paragraph IV Certification.

If an applicant has provided a Paragraph IV

Certification to the FDA, the applicant must also send notice of the Paragraph IV Certification to the holder of the NDA for the

approved drug and the patent owner once the application has been accepted for filing by the FDA.

The NDA holder or patent owner

may then initiate a patent infringement lawsuit in response to notice of the Paragraph IV Certification.

The filing of a patent

infringement lawsuit within 45 days of the receipt of a Paragraph IV Certification prevents the FDA from approving the ANDA or

505(b)(2) application until the earlier of 30 months from the date of the lawsuit, the applicant’s successful defense of

the suit, or expiration of the patent.

United States Medical Device Regulation

Medical devices, including diagnostic test

devices, also are subject to extensive and rigorous regulation by the FDA under the FDCA, as well as other federal and state regulatory

bodies in the United States, and laws and regulations of foreign authorities in other countries.

FDA requirements specific to medical

devices are wide ranging and govern, among other things, the design, development and manufacturing, human clinical trials, preclearance

or approval, advertising and promotion, and product import and export.

Unless an exemption applies, medical devices distributed

in the United States must receive either premarket clearance under Section 510(k) of the FDCA or premarket approval of a premarket

application (“PMA”).

During the COVID-19 public health emergency, the FDA has authorized COVID-19 diagnostic tests

under its Emergency Use Authorization authority.

Medical devices are classified into one of three classes—Class I, Class II,

or Class III—depending on the degree or risk associated with each medical device and the extent of control needed to

ensure safety and effectiveness.

an applicant has provided a Paragraph IV Certification to the FDA, the applicant must also send notice of the Paragraph IV Certification

to the holder of the NDA for the approved drug and the patent owner once the application has been accepted for filing by the FDA.

NDA holder or patent owner may then initiate a patent infringement lawsuit in response to notice of the Paragraph IV Certification.

filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV Certification prevents the FDA from approving

the ANDA or 505(b)(2) application until the earlier of 30 months from the date of the lawsuit, the applicant’s successful defense

of the suit, or expiration of the patent.

States Medical Device Regulation

devices, including diagnostic test devices, also are subject to extensive and rigorous regulation by the FDA under the FDCA, as well

as other federal and state regulatory bodies in the United States, and laws and regulations of foreign authorities in other countries.

FDA requirements specific to medical devices are wide ranging and govern, among other things, the design, development and manufacturing,

human clinical trials, preclearance or approval, advertising and promotion, and product import and export.

Unless an exemption applies,

medical devices distributed in the United States must receive either premarket clearance under Section 510(k) of the FDCA or premarket

approval of a premarket application (“PMA”).

During the COVID-19 public health emergency, the FDA has authorized COVID-19

diagnostic tests under its Emergency Use Authorization authority.

Medical devices are classified into one of three classes—Class I,

Class II, or Class III—depending on the degree or risk associated with each medical device and the extent of control

needed to ensure safety and effectiveness.

Medical devices deemed to pose relatively low risk are placed in either Class I or II.

II devices generally require the manufacturer to submit a premarket notification under Section 510(k) of the FDCA requesting

Class II devices generally require the manufacturer to submit a premarket notification under Section 510(k) of the FDCA requesting

permission for commercial distribution.

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Reimbursement

Potential sales of any of our product candidates,

if approved, will depend, at least in part, on the extent to which such products will be covered by third-party payors, such as

government health care programs, commercial insurance and managed healthcare organizations.

These third-party payors are increasingly

limiting coverage and/or reducing reimbursements for medical products and services.

A third-party payor’s decision to provide

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

Further, one payor’s determination

to provide coverage for a drug product does not assure that other payors will also provide coverage for the drug product.

sales of any of our product candidates, if approved, will depend, at least in part, on the extent to which such products will be covered

by third-party payors, such as government health care programs, commercial insurance and managed healthcare organizations.

These third-party

payors are increasingly limiting coverage and/or reducing reimbursements for medical products and services.

A third-party payor’s

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

Further, one payor’s

determination to provide coverage for a drug product does not assure that other payors will also provide coverage for the drug product.

In addition, the U.S.

government, state legislatures and foreign governments have continued implementing cost-containment programs, including

price controls, restrictions on reimbursement and requirements for substitution of generic products.

Adoption of price controls

and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures,

could further limit our future revenues and results of operations.

Decreases in third-party reimbursement or a decision by a third-party

payor to not cover a product candidate, if approved, or any future approved products could reduce physician usage of our products,

and have a material adverse effect on our sales, results of operations and financial condition.

In the United States, the Medicare Part D program

provides a voluntary outpatient drug benefit to Medicare beneficiaries for certain products.

We do not know whether our product

candidates, if approved, will be eligible for coverage under Medicare Part D, but individual Medicare Part D plans offer coverage

subject to various factors such as those described above.

Furthermore, private payors often follow Medicare coverage policies and

payment limitations in setting their own coverage policies.

Healthcare Laws and Regulations

Sales of our product candidates, if approved,

or any other future product candidate will be subject to healthcare regulation and enforcement by the federal government and the

states and foreign governments in which we might conduct our business.

The healthcare laws and regulations that may affect our

ability to operate include the following:

The federal Anti-Kickback Statute makes it illegal for any person or entity to knowingly and willfully, directly or indirectly, solicit, receive, offer, or pay any remuneration that is in exchange for or to induce the referral of business, including the purchase, order, lease of any good, facility, item or service for which payment may be made under a federal healthcare program, such as Medicare or Medicaid.

The term “remuneration”

has been broadly interpreted to include anything of value.

Federal false claims and false statement laws, including the federal civil False Claims Act, prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, for payment to, or approval by, federal programs, including Medicare and Medicaid, claims for items or services, including drugs, that are false or fraudulent.

Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) created additional federal criminal statutes that prohibit among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors or making any false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 and their implementing regulations, impose obligations on certain types of individuals and entities regarding the electronic exchange of information in common healthcare transactions, as well as standards relating to the privacy and security of individually identifiable health information.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services information related to payments or other transfers of value made to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

Also, many states have similar laws and regulations,

such as anti-kickback and false claims laws that may be broader in scope and may apply regardless of payor, in addition to items

and services reimbursed under Medicaid and other state programs.

Additionally, we may be subject to state laws that require pharmaceutical

companies to comply with the federal government’s and/or pharmaceutical industry’s voluntary compliance guidelines,

state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians

and other healthcare providers or marketing expenditures, as well as state and foreign laws governing the privacy and security

of health information, many of which differ from each other in significant ways and often are not preempted by HIPAA.

Additionally, to the extent that our product

is sold in a foreign country, we may be subject to similar foreign laws.

As of March 11, 2021, we employed a total

of 3 full-time employees, 1 employee consultant, and 1 part-time employee.

We are not a party to any collective bargaining agreements.

Adoption of price controls and cost-containment

measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit our future

revenues and results of operations.

Decreases in third-party reimbursement or a decision by a third-party payor to not cover a product

candidate, if approved, or any future approved products could reduce physician usage of our products, and have a material adverse effect

on our sales, results of operations and financial condition.

the United States, the Medicare Part D program provides a voluntary outpatient drug benefit to Medicare beneficiaries for certain products.

We do not know whether our product candidates, if approved, will be eligible for coverage under Medicare Part D, but individual Medicare

Part D plans offer coverage subject to various factors such as those described above.

Furthermore, private payors often follow Medicare

coverage policies and payment limitations in setting their own coverage policies.

Drug Designation

the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, which

is a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United

States for which there is no reasonable expectation that the cost of developing and making available in the United States a drug or biologic

for this type of disease or condition will be recovered from sales in the United States for that drug or biologic.

Orphan drug designation

must be requested before submitting an NDA or BLA.

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

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

The orphan drug designation does not convey any advantage in, or

shorten the duration of, the regulatory review or approval process.

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 drug exclusive approval (or exclusivity), which means that the FDA may not approve any other applications,

including a full NDA or BLA, to market the same drug 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 the 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.

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 condition.

Laws and Regulations

of our product candidates, if approved, or any other future product candidate will be subject to healthcare regulation and enforcement

by the federal government and the states and foreign governments in which we might conduct our business.

The healthcare laws and regulations

that may affect our ability to operate include the following:

federal Anti-Kickback Statute makes it illegal for any person or entity to knowingly and willfully, directly or indirectly, solicit,

receive, offer, or pay any remuneration that is in exchange for or to induce the referral of business, including the purchase, order,

lease of any good, facility, item or service for which payment may be made under a federal healthcare program, such as Medicare or

The term “remuneration” has been broadly interpreted to include anything of value.

false claims and false statement laws, including the federal civil False Claims Act, prohibits, among other things, any person or

entity from knowingly presenting, or causing to be presented, for payment to, or approval by, federal programs, including Medicare

and Medicaid, claims for items or services, including drugs, that are false or fraudulent.

Insurance Portability and Accountability Act of 1996 (“HIPAA”) created additional federal criminal statutes that prohibit

among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program,

including private third-party payors or making any false, fictitious or fraudulent statement in connection with the delivery of or

payment for healthcare benefits, items or services.

as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 and their implementing regulations,

impose obligations on certain types of individuals and entities regarding the electronic exchange of information in common healthcare

transactions, as well as standards relating to the privacy and security of individually identifiable health information.

federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which

payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report

annually to the Centers for Medicare & Medicaid Services information related to payments or other transfers of value made

to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family

many states have similar laws and regulations, such as anti-kickback and false claims laws that may be broader in scope and may apply

regardless of payor, in addition to items and services reimbursed under Medicaid and other state programs.

Additionally, we may be subject

to state laws that require pharmaceutical companies to comply with the federal government’s and/or pharmaceutical industry’s

voluntary compliance guidelines, state laws that require drug manufacturers to report information related to payments and other transfers

of value to physicians and other healthcare providers or marketing expenditures, as well as state and foreign laws governing the privacy

and security of health information, many of which differ from each other in significant ways and often are not preempted by HIPAA.

Additionally,

to the extent that our product is sold in a foreign country, we may be subject to similar foreign laws.

Our first clinical trial for BioLexa will be conducted

in Australia.

The TGA and the National Health and Medical Research Council set the GCP requirements

for clinical research in Australia, and compliance with these codes is mandatory.

Australia has also adopted international codes,

such as those promulgate by the International Council for Harmonization of Technical Requirements for Registration of Pharmaceuticals

for Human Use (“ICH”).

The ICH guidelines must be followed across all areas of clinical research, including those related

to pharmaceutical quality, nonclinical and clinical data requirements and trial designs.

The basic requirements for preclinical data to

support a first-in-human trial under ICH guidelines are applicable in Australia.

Requirements related to adverse event reporting in Australia

are similar to those required in other major jurisdictions.

trials conducted using “unapproved therapeutic goods” in Australia, being those which have not yet been evaluated by the

TGA for quality, safety and efficacy must occur pursuant to either the Clinical Trial Notification Scheme (“CTN Scheme”)

or the Clinical Trial Exemption Scheme (“CTX Scheme”).

In each case, the trial is supervised by a HREC, an independent

review committee set up under guidelines of the Australian National Health and Medical Research Council that ensures the protection of

rights, safety and well-being of human subjects involved in a clinical trial.

A HREC does this by reviewing, approving and providing

continuing examination of trial protocols and amendments, and of the methods and material to be used in obtaining and documenting informed

consent of the trial subjects.

A HREC reviews the scientific validity of the trial design, the balance of risk versus harm of the therapeutic

good, the ethical acceptability of the trial process, and approves the trial protocol.

The HREC is also responsible for monitoring the

conduct of the trial.

CTN Scheme broadly involves:

of preclinical laboratory and animal testing;

to a HREC, of all material relating to the proposed clinical trial, including the trial protocol;

institution or organization at which the trial will be conducted, referred to as the “Approving Authority”, giving final approval

for the conduct of the trial at the site, having regard to the advice from the HREC;

investigator submitting a ‘Notification of Intent to Conduct a Clinical Trial’ form (“CTN Form”) to the TGA.

must be signed by the sponsor, the principal investigator, the chairman of the HREC and a person responsible from the Approving Authority.

The TGA does not review any data relating to the clinical trial however CTN trials cannot commence until the trial has been notified

the CTX Scheme:

sponsor submits an application to conduct a clinical trial to the TGA for evaluation and comment;

sponsor must forward any comments made by the TGA Delegate to the HREC(s) at the sites where the trial will be conducted.

sponsor cannot commence a trial under the CTX Scheme until written advice has been received from the TGA regarding the application and

approval for the conduct of the trial has been obtained from an ethics committee and the institution at which the trial will be conducted.

The Therapeutic

Goods Act 1989 (the Act) requires that medical products, including pharmaceuticals, imported into, supplied in, or exported from

Australia be included in the Australian Register of Therapeutic Goods (“ARTG”).

In order to obtain registration of the

product on the ARTG:

must provide a product application containing adequate nonclinical data as well as data from adequate and well-controlled clinical trials

that demonstrate the safety and efficacy of the therapeutic product;

also must provide information demonstrating that the manufacture and quality of the therapeutic product complies with the principles

then evaluates the application data, taking into account recommendations from an advisory committee, such as the Advisory Committee on

Medicines, which makes recommendations to the TGA as to whether or not to grant approval to include the therapeutic product in the ARTG;

must decide to include the therapeutic product on the ARTG.

of March 28, 2022, we employed a total of 4 full-time employees, 1 employee consultant, and 1 part-time employee.

We are not a party

to any collective bargaining agreements.

We believe that we maintain good relations with our employees.

Our Corporate Information

We were incorporated as a Nevada corporation

on May 16, 2017.

Our principal executive offices are located at 1 Rockefeller Plaza, Suite 1039, New York, New York 10020 and our

telephone number is (646) 756-2997.

Available Information

Our website address is www.hoththerapeutics.com.

The contents of, or information accessible through, our website are not part of this Annual Report on Form 10-K, and our website

address is included in this document as an inactive textual reference only.

We make our filings with the U.S.

Securities and Exchange

Commission (“SEC”), including our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form

8-K and all amendments to those reports, available free of charge on our website as soon as reasonably practicable after we file

such reports with, or furnish such reports to, the SEC.

The public may read and copy the materials we file with the SEC at the

SEC’s Public Reference Room at 100 F Street, NE, Washington, DC 20549.

The public may obtain information on the operation

of the Public Reference Room by calling the SEC at 1-800-SEC-0330.

Additionally, the SEC maintains an internet site that contains

reports, proxy and information statements and other information.

The address of the SEC’s website is www.sec.gov.

information contained in the SEC’s website is not intended to be a part of this filing.

Corporate Information

were incorporated as a Nevada corporation on May 16, 2017.

Our principal executive offices are located at 1 Rockefeller Plaza, Suite

1039, New York, New York 10020 and our telephone number is (646) 756-2997.

website address is www.hoththerapeutics.com.

The contents of, or information accessible through, our website are not part of this

Annual Report on Form 10-K, and our website address is included in this document as an inactive textual reference only.

We make our filings

with the U.S.

Securities and Exchange Commission (“SEC”), including our Annual Report on Form 10-K, Quarterly Reports on

Form 10-Q, Current Reports on Form 8-K and all amendments to those reports, available free of charge on our website as soon as reasonably

practicable after we file such reports with, or furnish such reports to, the SEC.

The public may read and copy the materials we file

with the SEC at the SEC’s Public Reference Room at 100 F Street, NE, Washington, DC 20549.

The public may obtain information on

the operation of the Public Reference Room by calling the SEC at 1-800-SEC-0330.

Additionally, the SEC maintains an internet site that

contains reports, proxy and information statements and other information.

The address of the SEC’s website is www.sec.gov.

The information contained in the SEC’s website is not intended to be a part of this filing.

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