What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2022-04-15 compared with 2021-03-11 · 1096 added, 413 removed, 0 unchanged (100% of the section changed)

Merger and Asset Sale

Merger with Brooklyn Immunotherapeutics LLC

August 12, 2020, we entered into an agreement and plan of merger and reorganization (the “Merger Agreement”) with

Brooklyn Immunotherapeutics LLC (“Brooklyn”), a privately-held, biopharmaceutical company focused on exploring the

role that cytokine-based therapy can have in treating patients with cancer.

Pursuant to the Merger Agreement, subject to the satisfaction

or waiver of the conditions set forth in the agreement, BIT Merger Sub, Inc., our wholly-owned subsidiary formed solely for purposes

of carrying out the merger, will merge with and into Brooklyn, with Brooklyn surviving the merger as a wholly-owned subsidiary

of our company and Brooklyn’s members receiving newly issued shares of our common stock in exchange for their ownership

interests in Brooklyn (the “Merger”).

The Merger, if completed, will result in a change in control of NTN as described

The Merger is expected to close in mid- to late-March 2021.

filed a registration statement on Form S-4 relating to the Merger and the proposed sale of our assets to eGames.com Holdings LLC

(described further below) with the SEC and such registration statement was declared effective on February 3, 2021.

will be holding our special meeting of stockholders to consider the Merger, the Asset Sale (as defined below) and related proposals

on March 15, 2021 at 9:00 a.m., Pacific Time, unless postponed or adjourned to a later date or time.

Additional details regarding

the proposals and the special meeting are in the proxy statement/prospectus/consent solicitation statement relating to the special

meeting filed with the SEC on February 8, 2021 (the “Proxy Statement”).

the Merger is completed, NTN expects to change its name to Brooklyn ImmunoTherapeutics, Inc.

and the combined company will focus

on Brooklyn’s business of exploring the role that cytokine-based therapy can have on the immune system in treating patients

Upon completion of the Merger, the board of directors of the combined company is expected to consist entirely of

individuals designated by Brooklyn and the officers of the combined company are expected to be members of Brooklyn’s current

management team.

the Merger is completed, at the effective time of the Merger, Brooklyn’s members will exchange their equity interests in

Brooklyn for shares of NTN common stock representing between approximately 94.08% and 96.74% of the outstanding common stock of

NTN immediately following the effective time of the Merger on a fully diluted basis (less a portion of such shares which will

be allocated to Brooklyn’s banker, Maxim, in respect of the success fee owed to it by Brooklyn), and NTN’s stockholders

as of immediately prior to the effective time, will own between approximately 5.92% and 3.26% of the outstanding common stock

of NTN immediately after the effective time of the Merger on a fully diluted basis.

The exact number of shares to be issued in

the Merger will be determined pursuant to a formula in the Merger Agreement that takes into account the amount of Brooklyn’s

cash and cash equivalents as of the closing of the Merger and the amount by which NTN’s net cash is less than zero at the

The Merger Agreement does not include provisions providing for an adjustment to the total shares of NTN common stock

that Brooklyn’s members will be entitled to receive for changes in the market price of NTN common stock.

Merger Agreement contains customary representations, warranties and covenants made by NTN and Brooklyn, including covenants relating

to both parties using their commercially reasonable efforts to cause the transactions contemplated by the Merger Agreement to

be satisfied, as well as covenants regarding the conduct of their respective businesses between the date of signing of the Merger

Agreement and the closing.

of the Merger is subject to certain closing conditions including, among others, (i) the approval by our stockholders of the issuance

of shares of our common stock to Brooklyn’s members pursuant to the terms of the Merger Agreement and the change of control

of NTN resulting therefrom, (ii) the approval of the Merger and the transactions contemplated by the Merger Agreement by the beneficial

holders of the Class A membership units of Brooklyn, (iii) the amendment of our certificate of incorporation to provide voting

rights to the holders of our Series A Convertible Preferred Stock, (iv) Brooklyn having not less than $10 million in cash and

cash equivalents and not more than $750,000 of indebtedness for borrowed money at the closing, (v) our net cast at the closing

being not less than negative $3 million, and (vi) the shares of our common stock continuing to be traded on the NYSE American

until the effective time of the Merger and the approval for listing of the shares of our common stock to be issued pursuant to

the Merger Agreement on the NYSE American.

In addition, the obligation of each party to consummate the Merger is also conditioned

on the other party’s representations and warranties being true and correct (subject to certain materiality qualifications)

and the other party having performed in all material respects its obligations under the Merger Agreement.

Each party’s obligations

to consummate the Merger are further subject to the absence of a material adverse effect with respect to the other party since

the date of the Merger Agreement.

Merger Agreement contains certain termination rights for each party, including that either party may terminate the Merger Agreement

if the Merger has not been consummated by April 30, 2021, subject to extension under specified circumstances.

The Merger Agreement

also provides that, upon the termination of the Merger Agreement under specified circumstances, NTN or Brooklyn will be required

to pay the other party a $750,000 termination fee or reimburse the other party for up to $250,000 of its third party expenses.

Merger Agreement requires that NTN not solicit proposals relating to alternative transactions and not enter into discussions concerning

or provide confidential information in connection with alternative transactions.

These restrictions are subject to a “fiduciary

provision that allows NTN Buzztime under certain limited circumstances to provide confidential information to, enter

into discussions and negotiations with, and enter into an alternative transaction with a third party and/or to make a recommendation

change adverse to the Merger, which may result in payment of the termination fee described above.

connection with the Merger and the Merger Agreement, each of our directors and officers and certain beneficial holders of the

Class A membership interests of Brooklyn, including the managers and officers of Brooklyn, signed a Support Agreement, made and

entered into as of August 12, 2020, among NTN, Brooklyn, and each such person (the “Support Agreements”).

to the Support Agreements, each director, manager, and officer has agreed that he or she will not, until the termination date

of the Merger Agreement, sell or transfer any shares of our common stock or any of the beneficial interests in the Class A membership

interests of Brooklyn, respectively, that he or she owns or may acquire prior to the termination of the Merger Agreement.

such director, manager, and officer has further agreed that he or she will vote all shares of our common stock and all beneficial

interests in the Class A membership units in Brooklyn, respectively, owned by such individual in favor of the Merger and the transactions

contemplated by the Merger Agreement.

foregoing description of the Merger Agreement and the Support Agreements do not purport to be complete and is qualified in its

entirety by the full text of the agreements, copies of which have been filed with the SEC and are incorporated by reference in

The copies of the Merger Agreement and the Support Agreements filed with the SEC provide investors with information

regarding its terms.

Such copies are not intended to provide any other factual information about NTN or Brooklyn or otherwise

to modify or supplement any factual disclosures about NTN in its reports filed with the SEC.

The representations, warranties and

covenants of each party in the Merger Agreement have been made only for the purposes of, and were and are solely for the benefit

of the parties to, the Merger Agreement, may be subject to limitations agreed upon by the contracting parties, and may be subject

to standards of materiality applicable to the contracting parties that differ from those generally applicable to SEC filings,

and may have been used for purposes of allocating risk among the parties to the Merger Agreement.

Certain of the exhibits and

schedules that are a part of the Merger Agreement are not filed with the SEC and contain information that modifies, qualifies

and creates exceptions to the representations and warranties and certain covenants set forth in the Merger Agreement.

the representations and warranties may not describe the actual state of affairs at the date they were made or at any other time,

and investors should not rely on them as statements of fact.

Asset Sale to eGames.com

NTN announced the signing of the Merger Agreement, NTN also announced that it was continuing to explore the sale of substantially

all of the assets relating to its current business to provide additional capital and allow the combined company following the

closing of the Merger, if it closes, to be in a position to focus exclusively on Brooklyn’s business.

September 18, 2020, NTN and eGames.com Holdings LLC (“eGames.com”) entered into an asset purchase agreement (as amended

from time to time, the “APA”) pursuant to which, subject to the terms and conditions thereof, NTN will sell and assign

(the “Asset Sale”) all of its right, title and interest in and to the assets relating to its current business (the

“Purchased Assets”) to eGames.com.

The Purchased Assets comprise substantially all of NTN’s assets.

At the closing

of the Asset Sale, in addition to assuming specified liabilities of NTN, eGames.com will pay NTN $2.0 million in cash.

In connection

with entering into the APA, the sole owner of eGames.com absolutely, unconditionally and irrevocably guaranteed to NTN the full

and prompt payment when due of any and all amounts, from time to time, payable by eGames.com under the APA.

Asset Sale is expected to close in mid- to late-March 2021.

We will be holding our special meeting of stockholders to consider

the Merger, the Asset Sale and related proposals on March 15, 2021 at 9:00 a.m., Pacific Time, unless postponed or adjourned to

a later date or time.

Additional details regarding the proposals and the special meeting are in the Proxy Statement.

connection with entering into the APA, Fertilemind Management, LLC, an affiliate of eGames.com (“Fertilemind”), on

behalf of eGames.com, made a $1.0 million bridge loan to NTN.

On November 19, 2020, NTN, eGames.com and Fertilemind entered into

an omnibus amendment and agreement pursuant to which, among other things, eGames.com agreed to provide, or cause Fertilemind,

on behalf of eGames.com, to provide, an additional $0.5 million bridge loan to NTN on December 1, 2020, and the parties agreed

to increase the interest rate on the $1.0 million bridge loan Fertilemind made to NTN in September 2020 from 8% to 10% effective

December 1, 2020.

Fertilemind provided the $0.5 million bridge loan to NTN on December 1, 2020.

On January 12, 2021, NTN, eGames.com

and Fertilemind entered into a second omnibus amendment and agreement pursuant to which, among other things, eGames.com agreed

to provide, or cause Fertilemind, on behalf of eGames.com, to provide an additional $0.2 million bridge loan to NTN on January

Fertilemind provided the $0.2 million bridge loan to NTN on January 12, 2021.

The principal and accrued interest of

each of the loans provided by Fertilemind to NTN will be applied toward the $2.0 million purchase price at the closing of the

APA contains customary representations, warranties and covenants made by the parties, including covenants relating to both parties

using their efforts to cause the transactions contemplated by the APA to be satisfied, and covenants regarding the conduct of

NTN’s business between the date the APA was signed and the closing of the Asset Sale.

closing of the Asset Sale is subject to the satisfaction or waiver of certain closing conditions, including NTN obtaining, as

required by Delaware law, the approval of the Asset Sale by the holders of a majority of the outstanding shares of common stock

of NTN entitled to vote thereon.

Each party’s obligation to close the Asset Sale is also subject to other specified customary

conditions, including (1) the representations and warranties of the other party being true and correct (subject to certain materiality

qualifications, including qualifications with respect to a material adverse effect), and (2) the performance in all material respects

by the other party of its covenants and agreements in the APA required to be performed on or before the closing.

the parties to the APA agree to an earlier date, the closing of the Asset Sale is expected to occur as promptly as practicable

after the conditions to closing in the APA are satisfied or waived, and, if the conditions to closing the Merger are satisfied

or waived, immediately prior to the closing of the Merger.

to the APA, NTN may not, among other things, solicit proposals relating to alternative transactions or enter into discussions

concerning or provide confidential information in connection with alternative transactions (with an exception related to the Merger)

until the earlier of the termination of the APA and the closing of the Asset Sale.

These restrictions are subject to a “fiduciary

provision that allows NTN under certain limited circumstances to furnish confidential information to, enter into discussions

and negotiations with, and enter into an alternative transaction with a third party and/or to make a recommendation change adverse

to the Asset Sale, which may result in payment of the termination fee described below.

will be obligated to indemnify eGames.com against specified losses that eGames.com may incur following the Closing, subject to

the terms of the APA, including certain thresholds and caps on liability, and $100,000 will be deposited into an escrow account

to secure any such indemnification claims.

APA contains certain termination rights for each party, including that either party may terminate the APA if the asset sale has

not been consummated by April 30, 2021, subject to extension under specified circumstances.

The APA also provides that, upon the

termination of the APA under specified circumstances, NTN will pay eGames.com a $275,000 termination fee.

foregoing descriptions of the APA, the personal guaranty, and the promissory notes evidencing the bridge loans do not purport

to be complete and are qualified in their entirety by the full text of the APA, the personal guaranty, and such notes, copies

of which have been filed with the SEC and are incorporated by reference in this report.

The APA, the personal guaranty, and such

notes provide investors with information regarding its terms.

Such documents are not intended to provide any other factual information

about NTN or eGames.com or otherwise to modify or supplement any factual disclosures about NTN or eGames.com in their respective

reports filed with the SEC.

The representations, warranties and covenants of each party in the APA have been made only for the

purposes of, and were and are solely for the benefit of the parties to, the APA, may be subject to limitations agreed upon by

the contracting parties, and may be subject to standards of materiality applicable to the contracting parties that differ from

those generally applicable to SEC filings, and may have been used for purposes of allocating risk among the parties.

the exhibits and schedules that are a part of the APA are not filed with the SEC and contain information that modifies, qualifies

and creates exceptions to the representations and warranties and certain covenants in the APA.

Accordingly, the representations

and warranties may not describe the actual state of affairs at the date they were made or at any other time, and investors should

not rely on them as statements of fact.

Our Business and How We Talk About It

mentioned above, the Merger and Asset Sale are expected to close in mid- to late-March 2021.

If either the Asset Sale or the Merger

close, the description of our business contained in this report will no longer be our business following the closing of the Asset

Sale and/or Merger.

If the Merger is completed, the combined company will focus on Brooklyn’s business of exploring the

role that cytokine-based therapy can have on the immune system in treating patients with cancer.

If the Asset Sale is completed

but the Merger is not completed, NTN’s board of directors may elect to, among other things, attempt to find another reverse

merger partner or dissolve and liquidate its assets.

Because NYSE Regulation, Inc.

may begin delisting proceedings if NTN has

no assets or operations, and due to NTN’s limited cash and resources, NTN may be unable to identify and complete another

reverse merger and it would likely be required to dissolve and liquidate its assets.

In such case, NTN would likely be required

to pay all its debts and other obligations and to set aside certain reserves for potential future claims.

There can be no assurances

as to the amount or timing of available cash, if any, left to distribute to stockholders after paying its debts and other obligations

and setting aside funds for reserves.

deliver interactive entertainment and innovative technology to our partners in a wide range of verticals –

from bars and

restaurants to casinos and senior living centers.

By enhancing the overall guest experience, we believe we help our hospitality

partners acquire, engage, and retain patrons.

social fun and friendly competition, our platform creates bonds between our hospitality partners and their patrons, and between

patrons themselves.

We believe this unique experience increases dwell time, revenue, and repeat business for venues –

has also created a large and engaged audience which we connect with through our in-venue TV network.

Until the significant disruptions

to the restaurant and bar industry resulting from the COVID-19 pandemic, or the pandemic, that began in March 2020, over 1 million

hours of trivia, card, sports and arcade games were played on our network each month.

Since March 2020, approximately 100,000

hours per month of such games have been played on our network each month.

generate revenue by charging subscription fees to our partners for access to our 24/7 trivia network, by selling and leasing tablet

and hardware equipment for custom usage beyond trivia/entertainment, by selling digital-out-of-home (DOOH) advertising direct

to advertisers and on national ad exchanges, by licensing our entertainment and trivia content to other parties, and by providing

professional services such as custom game design or development of new platforms on our existing tablet form factor.

Until February

1, 2020, we also generated revenue by hosting live trivia events.

We sold all our assets used to host live trivia events in January

own several trademarks and consider the Buzztime®, Playmaker®, Mobile Playmaker, and BEOND Powered by Buzztime trademarks

to be among our most valuable assets.

These and our other registered and unregistered trademarks used in this document are our

Other trademarks are the property of their respective owners.

negative impact of the pandemic on the restaurant and bar industry was abrupt and substantial, and our business, cash flows

from operations and liquidity suffered, and continues to suffer, materially as a result.

In many jurisdictions, including

those in which we have many customers and prospective customers, restaurants and bars were ordered by the government to

shut-down or close all on-site dining operations in the latter half of March 2020.

Since then, governmental orders and

restrictions impacting restaurants and bars in certain jurisdictions were eased or lifted as the number of COVID-19 cases

decreased or plateaued, but as jurisdictions began experiencing a resurgence in COVID-19 cases, many jurisdictions reinstated

such orders and restrictions, including mandating the shut-down of bars and the closing of all on-site dining operations of

We have experienced material decreases in subscription revenue, advertising revenue and cash flows from

operations, which we expect to continue for at least as long as the restaurant and bar industry continues to be negatively

impacted by the pandemic, and which may continue thereafter if restaurants and bars seek to reduce their operating costs or

are unable to re-open even if restrictions within their jurisdictions are eased or lifted.

For example, at its peak,

approximately 70% of our customers had their subscriptions to our services temporarily suspended.

As of March 9, 2021,

approximately 11% of our customers remain on subscription suspensions.

As of December 31, 2020, 1,036 customers subscribed

to our service, a decrease of 404 customers, or 28%, from the 1,440 subscribers as of December 31, 2019.

We believe the year-over-year decrease was primarily due to

customers terminating their subscriptions or going out of business relating to the effects of the pandemic on their

response to the impact of the pandemic on our business, we implemented measures to reduce our operating expenses and preserve

capital, and we may implement additional measures in the future.

reduced our headcount (as of March 9, 2021, we had 22 employees, compared to 74 at December 31, 2019).

chief executive officer agreed to defer payment of 45% of his base salary between May 1, 2020 and October 31, 2020 until the

earlier of October 31, 2020 or such time as our board of directors determines in good faith that we are in the financial position

to pay his accumulated deferred salary.

All such deferred base salary payments were made by November 6, 2020.

terminated the lease for our corporate headquarters, resulting in a reduction in our future cash obligations under the lease

by approximately $3.4 million (see Note 16 to our audited consolidated financial statements included herein).

substantially eliminated all capital projects and are aggressively managing our expenditures to limit further cash outlays

and manage our working capital.

April 2020, we received a loan of approximately $1,625,000 under the Paycheck Protection Program of the Coronavirus Aid, Relief,

and Economic Security Act administered by the U.S.

Small Business Administration.

The loan matures on April 18, 2022 and bears

interest at a rate of 1.0% per annum.

We began making monthly interest only payments in November 2020.

One final payment of all

unforgiven principal plus any accrued unpaid interest is due at maturity.

In November 2020, we were informed by our lender that

the U.S Small Business Administration approved the forgiveness of approximately $1,093,000 of the $1,625,000 loan, leaving a principal

balance of approximately $532,000.

For additional information, see the section entitled “Liquidity and Capital Resources—Paycheck

Protection Program Loan”

in “ITEM 7.

Management’s Discussion and Analysis of Financial Condition and Results

of Operations”

of Part II of this report.

amounts outstanding under our term loan we entered into with Avidbank in September 2018 were paid in full on December 31, 2020

and we have no further obligations to Avidbank.

January 2020, we sold all of our assets used to conduct the live hosted knowledge-based trivia events known as Stump!

OpinioNation for approximately $1.4 million in cash.

principal product and service is our interactive entertainment system that offers trivia, card, sports and arcade games through

an extended network platform.

Generally, as part of the subscription to our platform, we provide the equipment for the platform

to network subscribers (including tablets, cases and charging trays for the tablets), though we have also leased such equipment

to certain network subscribers.

We also monetize our network by offering it as an advertising platform through which parties can

advertise their products and services across the thousands of TV and tablet screens in our network.

In 2017, we began licensing

our content to customers to be installed on equipment they obtain from other parties.

In 2018, we began selling the tablets, cases

and charging trays for the tablets used in our platform to customers who may not subscribe to our network but who can use the

equipment in their business for other purposes.

In 2019, we redesigned the personal computer installed in venues to stream our

content to televisions and tablets within the venue.

The redesigned personal computer, which we call Site Hub, has a smaller form

factor (about the size of a deck of cards) compared to our historical personal computer.

During the second quarter of 2019, we

began field testing a lower cost, entry-level tablet product offering that we call Buzztime Basic.

The brains behind Buzztime

Basic is Site Hub.

We have deployed Buzztime Basic on a market-by-market basis and as of March 9, 2021, we were in approximately

212 locations.

In 2019, we also released our mobile trivia app, allowing our customers’

patrons to play our trivia

games on their mobile devices in addition to on our tablets.

The app is the primary means of playing our trivia games in Buzztime

the first quarter of 2019, we rolled out our new, modernized advertising system, which gives us access to ad buying platforms

where digital advertising inventory is bought and sold on public exchanges and private marketplaces.

We work with advertising

sales companies to help us improve our advertisement sales and with an advertisement technology company to improve our ad loading,

management, and delivery and testing capabilities.

We can use advertising to monetize Buzztime Basic, as well as our entire network.

We had quarter-over-quarter advertising sales and revenue growth during 2019.

In 2020, our advertising sales and revenue was materially

adversely impacted as a result of the pandemic.

primary network subscribers are bars and restaurants in North America, which we target directly through our internal sales organization.

In April 2016, we began offering our platform in adjacent markets, such as senior centers and casinos, which we target through

third parties who have existing business relationships with potential customers in such markets.

primarily develop the content and functionality available through our platform internally.

We use an Android-based tablet customized

to our specifications by a single unaffiliated third-party manufacturer.

Such third-party also manufactures the cases and charging

trays for the tablets and sources the raw materials used to manufacture those cases and trays.

face direct competition in venues and face competition for total entertainment and marketing dollars in the marketplace from other

companies offering similar content and services.

A relatively small number of direct competitors are active in the hospitality

marketing services and entertainment markets, including UpShow, The Chive and other broadcast entertainment service providers.

Competing forms of technology, entertainment, and marketing available in hospitality venues include games, apps and other forms

of entertainment offerings available directly to consumers on their smart phones and tablets, on-table bar and restaurant entertainment

systems, music and video-based systems, live entertainment and live trivia games, cable, satellite and pay-per-view programming,

coin-operated single-player games/amusements, and traffic-building promotions like happy hour specials.

table below sets forth the approximate amount of revenue we generated from Buffalo Wild Wings corporate-owned restaurants and

its franchisees during the years ended December 31, 2020 and 2019, and the percentage of total revenue that such amount represents

for such periods.

The decrease reflects the loss of 1,088 Buffalo Wild Wings corporate-owned restaurants and franchisees in

November 2019, when their agreements with us terminated in accordance with their terms.

Buffalo Wild Wings revenue

Percent of total revenue

of December 31, 2020 and 2019, approximately $108,000 and $158,000, respectively, was included in gross accounts receivable from

Buffalo Wild Wings corporate-owned restaurants and its franchisees.

generally do not have a significant backlog because we normally can deliver and install new systems within the delivery schedule

requested by customers (generally within three to four weeks).

Trademarks, Copyrights and Patents

majority of the gaming content available on our platform is internally developed.

The balance is licensed from third parties.

We also license third party content for our pay-to-play and free-to-consumer games lobby.

The amounts paid for such third-party

licensed content was not material during either of the years ended December 31, 2020 or 2019.

intellectual property assets, including patents, trademarks, and copyrights, are important to our business and, accordingly, we

actively seek to protect the proprietary technology we consider important to our business.

No single patent or copyright is solely

responsible for protecting our products.

keep confidential as trade secrets our technology, know-how and software.

Most of the hardware we use in our platform is purchased

from a third party and customized for use with our service.

We enter into agreements with third parties with whom we conduct business,

which contain provisions designed to protect our intellectual property and to limit access to, and disclosure of, our proprietary

We also enter into confidentiality and invention assignment agreements with our employees and contractors.

believe the duration of our patents is adequate relative to the expected lives of our products.

We consider the following United

States and Canadian patents to be important to the protection of our products and service:

Expiration Date

System and method for television-based services

Interactive gaming via mobile playmaker

2741999 (CAN)

Interactive gaming via mobile playmaker

User-controlled entertainment system, apparatus and method

Electronic menu system and method

System and method for television-based services

Interactive gaming via mobile playmaker

User-controlled entertainment system, apparatus and method

Electronic check splitting system, method and apparatus

have trademark protection for the names of our key proprietary programming, products, and services to the extent that we believe

trademark protection is appropriate.

We are expanding our efforts to protect these investments.

We consider the Buzztime, Playmaker,

Mobile Playmaker and PlayersPlus trademarks and our other related trademarks to be valuable assets, and we seek to protect them

through a variety of actions.

Our content, branding, and some of our game titles, such as Countdown, SIX, and Showdown are also

protected by copyright and trademark law.

cost of compliance with federal, state, and local laws has not had a material effect on our capital expenditures, earnings, or

competitive position to date.

In December 2012, we received approval from the Federal Communications Commission, or the FCC, for

our tablet charging trays, and in September 2015, we received FCC approval for our third-generation tablet cases with and without

payment electronics.

The tablets we currently use have been certified by its manufacturer.

addition to laws and regulations applicable to businesses generally, we are also subject to laws and regulations that apply directly

to the interactive entertainment and product marketing industries.

Additionally, state and federal governments may adopt additional

laws and regulations that address issues related to certain aspects of our business such as:

lottery and alcohol beverage control regulations;

distribution of specific material or content;

characteristics and quality of interactive entertainment products and services.

part of our service, we operate games of chance and skill, including several interactive card games, such as Texas Hold’em

These games are subject to regulation in many jurisdictions, and some games are restricted in certain jurisdictions.

laws and regulations that govern these games, however, vary from jurisdiction to jurisdiction and are subject to legislative and

regulatory change, as well as law enforcement discretion.

Most of our games are played solely for fun and winner recognition,

however, we recently began awarding nominal cash prizes to winners of certain trivia competitions.

We may find it necessary to

eliminate, modify, or cancel certain of our offerings in certain jurisdictions based on changes in law, regulations and law enforcement

discretion, which could result in additional development costs and/or the possible loss of customers and revenue.

Site Access to SEC Filings

annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and amendments to those reports, and

proxy statements and other information we file or furnish pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of

1934, as amended (the “Exchange Act”) are available on our website at www.buzztime.com/business/investor-relations/

under the heading SEC Filings as soon as reasonably practicable after we electronically file such reports with,

or furnish them to, the SEC.

In addition, we make available on that same website under the heading Corporate Governance

our (i) our code of conduct and ethics;

(ii) our corporate governance guidelines;

and (iii) the charter of each active committee

of our board of directors.

We intend to disclose any amendment to, or a waiver from, a provision of our code of conduct and ethics

that applies to our principal executive officer, principal financial officer, principal accounting officer or controller, or persons

performing similar functions and that relates to any element of the code of ethics definition enumerated in paragraph (b) of Item

406 of Regulation S-K by posting such information on that website.

SEC maintains a website at www.sec.gov that contains reports, proxy and information statements, and other information

regarding companies that file electronically with the SEC, including our company.

of March 9, 2021, we had 22 full-time employees.

We also engage independent contractors for specific projects.

None of our employees

are represented by a labor union, and we believe our employee relations are satisfactory.

Corporate History

Buzztime, Inc.

was incorporated in Delaware in 1984 as Alroy Industries and changed its corporate name to NTN Communications,

The name was changed to NTN Buzztime, Inc.

in 2005 to better reflect the growing role of the Buzztime consumer brand.

On March 25, 2021, BIT Merger Sub, Inc., a wholly owned subsidiary of Brooklyn (then known as NTN Buzztime, Inc.) merged with and into Brooklyn LLC, with Brooklyn LLC surviving as a wholly

owned subsidiary of Brooklyn.

This transaction, which we refer to as the Merger, was completed in accordance with the terms of an agreement and plan of merger and reorganization dated August 12, 2020 among Brooklyn (then known as NTN Buzztime,

Inc.), BIT Merger Sub, Inc.

and Brooklyn LLC.

In accordance with such agreement and plan of merger, on March 25, 2021, Brooklyn amended its restated certificate of incorporation in order to effect:

prior to the Merger, a reverse stock split of its common stock, par value $0.005 per share, at a ratio of one-for-two;

following the Merger, a change in its corporate name from “NTN Buzztime, Inc.” to “Brooklyn ImmunoTherapeutics, Inc.”

On March 26, 2021, we sold the rights, title and interest in and to the assets relating to the business operated under the name “NTN Buzztime, Inc.” prior to the Merger to eGames.com Holdings

LLC, or eGames.com, in exchange for eGames.com’s payment of a purchase price of $2.0 million and assumption of specified liabilities relating to such pre-Merger business.

This transaction, which we refer to as the Disposition, was completed in

accordance with the terms of an asset purchase agreement dated September 18, 2020, as amended, between us and eGames.com.

The Merger has been accounted for as a reverse acquisition in accordance with United States generally accepted accounting principles, or GAAP.

Under this method of accounting, Brooklyn LLC was

deemed the “acquiring” company and Brooklyn (then known as NTN Buzztime, Inc.) was treated as the “acquired” company for financial reporting purposes.

Operations prior to the Merger are those of Brooklyn LLC, and the historical financial

statements of Brooklyn LLC became the historical financial statements of Brooklyn with respect to periods prior to the completion of the Merger.

Our principal executive offices are located at 10355 Science Center Drive, Suite 150, San Diego, CA 92121 and our phone number is (212) 582-1199.

We maintain a website at www.brooklynitx.com.

Information contained on, or accessible through, our website is not a part of and is not incorporated by

reference into this Annual Report on Form 10-K.

We are a clinical-stage biopharmaceutical company focused on exploring the role that cytokine-based therapy can have on the immune system in treating patients with cancer, both as a single

agent and in combination with other anti-cancer therapies.

We are seeking to develop IRX-2, a novel cytokine-based therapy, to treat patients with cancer.

We also are exploring opportunities to advance oncology, blood disorder, and monogenic

disease therapies using gene-editing and cell therapy technology through a license with Factor Bioscience Limited, or Factor, and through our acquisition of Novellus, Inc.

and Novellus, Ltd.

in July 2021, which we refer to as the Acquisition.

IRX-2 is a mixed, human-derived cytokine product with multiple active constituents including Interleukin-2, or IL2, and other key cytokines.

Together, these cytokines are believed to signal,

enhance and restore immune function suppressed by the tumor, thus enabling the immune system to attack cancer cells, unlike many existing cancer therapies, which rely on targeting the cancer directly.

IRX-2 is prepared from the supernatant of

pooled allogeneic peripheral blood mononuclear cells, known as PBMCs, that have been stimulated using a proprietary process employing a specific population of cells and a specific mitogen.

While IRX-2 is a cytokine mixture, one of its active components is IL2, a cytokine-signaling molecule with pleiotropic effects on the immune system.

IL2 is a protein that regulates the

activities of white blood cells (leukocytes, including lymphocytes) that are responsible for immunity.

IL2 is part of the body’s natural response to microbial infection, and in discriminating between foreign, or non-self and “self,” IL2 mediates

its effects by binding to IL2 receptors, which are expressed by lymphocytes.

The major sources of IL2 are activated CD4 + T lymphocytes and activated CD8 + T lymphocytes.

Unlike existing recombinant IL2 therapies, IRX-2 is derived from human blood cells.

We believe this may promote better tolerance, broader targeting and a natural molecular conformation leading

to greater activity, and may permit low physiologic dosing, rather than the high doses needed in other existing IL2 therapies.

Regarding IRX-2 development, our strategy is:

Advance our product candidate IRX-2 through clinical development.

IRX-2 is a human blood cell-derived cytokine therapy being studied for multiple types of cancer,

including squamous cell cancer of the head and neck.

Enrollment in the ongoing Phase 2b INSPIRE trial, or the INSPIRE trial, has been completed, with top-line data estimated to be available by the third quarter of 2022.

Advance additional studies.

Once INSPIRE trial data are released, we plan to use those results as a catalyst in addition to data from the other clinical trials in

the program, see “—Clinical Program” below, with multiple data read-outs anticipated in 2022 and later.

Pursue partnerships to advance the IRX-2 clinical program .

We are pursuing partnership opportunities with certain leading biopharmaceutical companies for the

development and commercialization of IRX-2.

Regulatory strategy.

We believe that our assets may present opportunities for potential breakthroughs in the treatment of cancer and other indications.

endeavor to seek breakthrough therapy designation with regulatory agencies for IRX-2 for one or more indications.

Intellectual Property .

We continue to pursue additional intellectual property based on data from our IRX-2 clinical studies.

Pre-Clinical Results

Our findings to date from our nonclinical studies of IRX-2 include murine acute toxicology as well as acute and chronic toxicology in non-human primates.

These studies detected circulating

associated cytokines yet were associated with benign toxicological findings.

Clinical Program

IRX2 currently remains under development and has not yet been approved for marketing authorization in any jurisdiction.

The ongoing company sponsored development program is investigating use of

IRX2 as an immunotherapeutic neoadjuvant (pre-surgical) and adjuvant (post-operative) treatment for advanced head and neck squamous cell carcinoma, or (“HNSCC”).

Studies in other indications and combinations are being pursued in the investigator

sponsored study program.

The HNSCC development program is being conducted under U.S.

Food and Drug Administration (“FDA”) Investigational New Drug (IND) 11137 filed on June 30, 2003 and is ongoing.

The HNSCC program

has received fast track designation, approved November 7, 2003, and orphan drug designation, conferred on July 7, 2005, from the FDA.

We have not submitted a request for orphan drug designation in the European Union, although we may seek such

designation in the future.

Clinical studies in humans with HNSCC involving IRX‑2 show immune marker activation in patients treated with IRX‑2.

In a prior Phase 2a clinical trial, a correlation was shown between marker

activation and disease-free survival in head and neck cancer.

Results from this study were used to support the initiation of the INSPIRE trial involving 105 patients with HNSCC.

Details of this trial can be found at clinicaltrials.gov (NCT02609386).

The trial study schema can be found below.

Historical Background of the Inspire Study

The IRX-2 regimen has been studied in patients HNSCC in two previous open-label, multi-center studies.

Also, a phase 1 trial evaluated the IRX-2 regimen as a therapy for advanced disease, which

reported that the IRX-2 regimen was well tolerated.

In 2011, results were reported for a Phase 2a trial of IRX-2.

This trial was an open-label study involving 27 patients, 26 of whom completed the study.

The primary endpoint of the study was to

further evaluate the safety and efficacy of the immunotherapy regimen including IRX-2 in the neoadjuvant setting in previously untreated patients with advanced (Stage II to IVa) HNSCC.

The primary study objective was to demonstrate the safety of

this immunotherapy regimen based on adverse events (“AEs”), changes in clinical laboratory measures (hematology, chemistry, and urinalysis), vital signs, and physical examinations.

Secondary objectives were clinical, pathologic, and radiographic

tumor response;

and patient disease-free survival (“DFS”) and overall survival (“OS”).

Most recombinant cytokines, such as IL-2, are tested in the same manner as traditional oncology drugs, where the maximum tolerated dose is sought.

Typical cytokine therapies in cancer treatment

use extremely high doses, in the millions of units per administration.

Thus, AEs such as fever, hypotension, malaise, anemia, leukopenia, and hepatic and renal dysfunction are commonly reported, and often lead to discontinuation of the treatment.

IV administration of cytokines is frequently associated with an acute phase reaction characterized by rigors, fever, an increase in neutrophils, a decrease in lymphocytes, and changes in hormone levels.

By contrast, the IRX-2 regimen, which

contains physiologic quantities of cytokines, showed greatly improved tolerability over typical recombinant cytokine therapies.

The results of the Phase 2a study were published in December 2011 in the journal Head and Neck.

The article reported that IRX-2 showed an immunologically mediated antitumor effect, suggested by

pronounced lymphocytic infiltration.

Lymphocytic infiltration was measured by a 100-mm Visual Analog Scale (“VAS”) score, in which 100 mm signified lymphocyte infiltration of the entire primary tumor section and 0 mm signified no lymphocyte

infiltration in the tumor specimen.

The mean VAS score for all 24 patients was 22.6 mm on the samples obtained at surgery.

Patients were grouped into a low VAS score (below the overall mean) and high VAS score (above the overall mean) cohorts.

There were 14 patients in the low VAS score cohort with scores between 2 and 21 (median of 9.5), and there were 10 patients in the high VAS score cohort with scores between 27 and 66 (median of 37.0).

Patients in the high-LI group included fewer

oral cavity patients (50% in high LI vs 60% in low LI) but were similar with respect to tumor sites.

Seventy percent of high-LI patients were stage IV, whereas only 60% of low LI were stage IV.

The LI score was used to determine whether the

degree of LI correlated with survival.

Patients with a high-LI score had an improved survival trend compared to those with low LI, and superior to the survival rate for the combined overall group.

Interestingly, LI in resected tumor specimens was considered high in 40% of the patients.

The 10 patients with a high-LI score showed an improved survival trend in comparison to the low-LI

group (n = 15) and to the entire study population (n = 26).

It is difficult to directly compare these subgroups, because there was some imbalance, with a slightly higher per-centage of oral cavity patients in the low-LI group.

However, in the

absence of a randomized control, it is impossible to directly attribute the LI to the immuno-therapy regimen.

In addition, tumor reductions were observed at the end of the 21-day regimen in 11 patients, and a 75% reduction of glycolytic activity

in the tumor and lymph nodes on posttreatment PET scans in one patient.

With regard to the primary endpoint, eight serious adverse events (SAEs) were reported during treatment and the 30-day postoperative period in 7 patients, including 3 patients with aspiration

pneumonia, 1 patient with asthma exacerbation secondary to upper respiratory infection, 1 patient with a postoperative wound infection, 1 patient with a neck abscess, and 1 patient with an episode of alcohol withdrawal.

Only 1 case of aspiration

pneumonia was deemed life threatening (grade 4).

None of the SAEs was considered related to treatment except for the postoperative wound infection, which was considered possibly related.

Other minor (grade 1 or 2) AEs included headache (30%),

injection-site pain (22%), nausea (22%), constipation (15%), dizziness (15%), fatigue (11%), and myalgia (7%).

After over more than 36 months of follow-up, 11 of the 27 patients enrolled in the Phase 2a study had experienced tumor relapse (n = 1) or death (n = 10).

The pattern of first HNSCC relapse

included 3 patients with primary site recurrence, 2 with recurrences in the neck, and 2 with distant metastases.

Of the 10 patients who died, 6 died of cancer (1 from a new primary) and 4 died of other causes.

The 1-year, 2-year, and 3-year DFS

probabilities after surgery were 72%, 64%, and 62%, respectively.

Of the 26 patients whose primary tumor was resected surgically, 2 patients died during the first year and 5 patients died during the second year after surgery.

The probability of

surviving after surgery was 92% the first year, 73% the second year, and 69% the third year, which was considered to be an encouraging survival rate compared to historical norms in patients with HNSCC.

A second finding of the study was that some tumors showed some decrease in overall size after the immunotherapy regimen.

Overall tumor shrinkage was modest, although in 4 patients, independent,

objective imaging documented a greater than 10% decrease in tumor size.

This was unexpected and encouraging after only 3 weeks of presurgical neoadjuvant immunotherapy.

No patient achieved a true partial response by modified Response Evaluation

Criteria in Solid Tumors (RECIST) criteria.

Increases in tumor measurements were also seen in some patients, but most patients showed negligible change in tumor dimensions.

We believe that these findings suggest the safety of the neoadjuvant

regimen, although final decisions on whether a drug product is safe and effective can only be made by the FDA.

The phase 2a trial did not include a randomized control cohort.

However, the manuscript published in Head & Neck in December 2011 stated the authors’ belief that the safety results and

feasibility of this immunotherapy regimen were intriguing enough to warrant further study and appropriate comparison in a randomized trial.

The INSPIRE study is an open label, randomized, multi-center, multi-national Phase 2b clinical trial intended for patients with Stage II, III or IVA untreated SCC of the oral cavity who are

candidates for resection with curative intent.

Subjects were randomized 2:1 to either Regimen 1 or Regimen 2 and treated for 21 days prior to surgery and then postoperatively with a booster regimen given every three months for one year (a total

of four times.)

IRX-2 Regimen with cyclophosphamide, indomethacin, zinc-containing multivitamins, omeprazole and IRX-2 as neoadjuvant and adjuvant therapy.

Regimen 1 with cyclophosphamide, indomethacin, zinc-containing multivitamins, omeprazole but without IRX-2 as neoadjuvant and adjuvant therapy.

Treatments were allocated to study subjects using minimization with a stochastic algorithm based on the range method.

Minimization will account for the major prognostic factors for SCC of the

oral cavity (T and N stage) and study center to avoid imbalances in treatment allocation within centers.

Postoperatively, subjects first received standard adjuvant radiation or chemoradiation therapy as determined by the investigators per NCCN guidelines, and then also received Booster Regimen 1

or 2 as determined in the prior randomization.

Subjects will be followed for the Primary, Secondary and Exploratory endpoints.

Protocol mandated follow-up will end four years after randomization of the last patient.

The Neoadjuvant IRX-2 Regimen is a 21-day pre-operative regimen of cyclophosphamide on Day 1, indomethacin, zinc-containing multivitamins and omeprazole on Days 1-21, and subcutaneous IRX-2

injections in bilateral mastoid insertion regions for 10 days between Days 4 and 21, as shown in the table below:

Route of Administration

Treatment Days

Cyclophosphamide

230 units daily (Bilateral injections of 115 units)

Subcutaneous at or near the mastoid insertion of both sternocleidomastoid muscles

Any 10 days between Days 4 and 21

Zinc-Containing Multivitamins

1 tablet containing 15-30 mg of zinc

The Booster IRX-2 Regimen is given at 3, 6, 9 and 12 months (-14 to +28 days) after surgical resection.

It is a 10- day post-operative regimen of cyclophosphamide on Day 1, indomethacin,

zinc-containing multivitamins and omeprazole on Days 1-10 and subcutaneous IRX-2 injections in bilateral deltoid regions for 5 days between Days 4 and 10 as shown in the table below:

Route of Administration

Treatment Days

Cyclophosphamide

Every 3 months.

230 units daily (Bilateral injections of 115 units)

Subcutaneous into bilateral deltoid regions

Any 5 days between Days 4 and 10

Every 3 months.

Zinc-Containing Multivitamins

1 tablet containing 15-30 mg of zinc

Every 3 months.

Regimen 2, the control arm of the study, is identical, except that subjects will not receive IRX-2.

The primary objective of the study is to determine if the event-free survival (EFS) of subjects treated with Regimen 1 is longer than for subjects treated with Regimen 2.

The secondary

objections of the study are (i) to determine if OS of subjects treated with Regimen 1 is longer than for subjects treated with Regimen 2, (ii) to compare the safety of each Regimen, and (iii) to compare the feasibility of each booster regimen.

Other Indications

Other than the phase 2b INSPIRE trial, all clinical studies using IRX-2 are investigator-sponsored studies for which we are providing IRX‑2 as the study drug and financial support to conduct

These studies include:

Monotherapy studies:

BR-101 - A study involving 16 patients with neoadjuvant breast cancer performed at the Providence Portland Medical Center.

Details of this trial can be found at clinicaltrials.gov

(NCT02950259).

CIN-201 - An open label single arm Phase 2 trial of the IRX‑2 regimen in women with cervical squamous intraepithelial neoplasia 3 or squamous vulvar intraepithelial neoplasia 3.

Details of this trial can be

found at clinicaltrials.gov (NCT03267680).

Combination studies:

BAS-104 - A basket study originally intended to enroll 100 patients with metastatic bladder, renal, non-small cell lung cancer, or NSCLC, melanoma, and head and neck cancer being held at the Moffitt

Cancer Center, using IRX‑2 in conjunction with Opdivo ® (Nivolumab), an immunotherapy cancer treatment marketed by Bristol-Myers Squibb Company.

trial was discontinued after 11 subjects were enrolled due to insurance reimbursement challenges.

Details of this trial can be found on clinicaltrials.gov (NCT03758781).

HCC-107 - A study involving 28 patients with metastatic hepatocellular carcinoma, or HCC, being held at City of Hope Medical Center, HonorHealth Research Institute, and Texas Oncology at Baylor

Simmons Cancer Center using IRX‑2 in conjunction with Opdivo ® , a cancer treatment marketed by Bristol-Myers Squibb Company.

this trial can be found at clinicaltrials.gov (NCT03655002).

GI-106 - A study involving 20 patients with metastatic gastric and gastroesophageal junction cancers (GI) being held at City of Hope Medical Center, HonorHealth Research Institute, and Texas Oncology

at Baylor Charles A.

Simmons Cancer Center using IRX‑2 in conjunction with Keytruda ® (Pembrolizumab), an immunotherapy cancer treatment marketed by

Details of this trial can be found at clinicaltrials.gov (NCT03918499).

MHN-102 - A study involving 15 patients with metastatic head and neck cancer being held at the H.

Lee Moffitt Cancer Center and Research Institute and University of Michigan Health System using IRX‑2 in

conjunction with Imfinzi (Durvalumab), a cancer treatment marketed by AstraZeneca plc.

Details of this trial can be found at clinicaltrials.gov (NCT03381183).

BR-202 - A study involving 30 patients with neoadjuvant triple negative breast cancer, held at the Providence Portland Medical Center using IRX‑2 in conjunction with a programmed cell death protein 1, or

PD1, and chemotherapy treatments.

Details of this trial can be found at clinicaltrials.gov (NCT04373031).

Impact of COVID-19 Pandemic

The development of our product candidates has been, and could continue to be, disrupted and materially adversely affected by past and continuing impacts of the COVID-19 pandemic.

largely a result of measures imposed by the governments and hospitals in affected regions, businesses and schools were suspended due to quarantines intended to contain this outbreak.

The spread of COVID-19 from China to other countries resulted

in the Director General of the World Health Organization declaring COVID-19 a pandemic in March 2020.

While the constraints of the pandemic are being lifted, we are still assessing the longer-term impact of the COVID-19 pandemic on our

development plans, and on the ability to conduct our clinical trials.

COVID-19 could continue to disrupt production and cause delays in the supply and delivery of products used in our operations, may affect our operations, including the conduct

of clinical studies, or the ability of regulatory bodies to grant approvals or supervise our candidates and products, may further divert the attention and efforts of the medical community to coping with the COVID-19 and disrupt the marketplace in

which we operate and may have a material adverse effects on our operations.

COVID-19 may also affect our employees and employees and operations at suppliers that may result in delays or disruptions in supply.

In addition, a recession or market

correction resulting from the spread of COVID-19 could materially affect our business and the value of our common stock.

Additionally, if the COVID-19 pandemic has a significant impact on our business and financial results for an extended period

of time, our liquidity and cash resources could be negatively impacted.

The extent to which the COVID-19 pandemic and ongoing global efforts to contain its spread will impact our operations will depend on future developments, which are highly

uncertain, and include the duration, severity and scope of the pandemic and the actions taken to contain or treat the COVID-19 pandemic.

Further, the specific clinical outcomes, or future pandemic related impacts of emerging COVID-19 variants

cannot be reliably predicted.

The patients in our clinical trials have conditions that make them especially vulnerable to COVID-19, and as a result we have seen slowdowns in enrollment in our clinical trials.

INSPIRE trial in patients with squamous cell carcinoma of the oral cavity is fully populated, our other clinical studies are likely to continue to encounter delays in enrollment as a result of the pandemic.

Engineered Cellular and Genetic Medicines

We are advancing our gene-editing and cell therapy technology in oncology, blood disorders and monogenic disorders through a license with Factor and through the Acquisition of Novellus, Inc.

and Novellus, Ltd.

in July 2021.

We expect that the first generation product candidates resulting from the Acquisition will be derived from unedited (that is, not gene modified), induced pluripotent stem cells (“iPSC”)-derived allogeneic

mesenchymal stem cells (“iMSC”).

We expect to begin preclinical development of iMSC for clinical indications for which inhibiting inflammation and/or supporting recovery of bone marrow stromal cells is required.

The prior work of Novellus and

NoveCite with iMSC shows evidence for preclinical efficacy in inflammatory conditions (for example, acute respiratory distress syndrome, or ARDS).

Interactions with the FDA provided guidance on Chemistry, Manufacturing and Controls (“CMC”), and

manufacturing plans, which will be undertaken in a similar manner for additional iMSC applications.

We expect that second generation iMSC products will involve gene editing, for which we anticipate using the stepwise addition of genes provided by

the in-licensed Factor Bioscience gene editing machinery, NoveSlice, to efficiently place genes and regulatory sequences into safe harbor locations.

Development of processes to advance CMC and manufacturing will follow the experience from first

generation iMSC products.

We expect clinical indications for gene-modified iMSC will include solid tumors and other conditions associated with episodic and/or chronic inflammation.

We are also exploring opportunities to advance in vivo gene

therapies for monogenic and other diseases by combining the NoveSlice gene editing technology in combination with ToRNAdo TM , the in-licensed lipid nanoparticle (or

“LNP”) technology.

Pluripotent Stem Cell-Derived MSC

MSC, also known as mesenchymal stromal cells, were originally discovered and isolated from bone marrow in the 1970s and have been isolated from various tissue sources including muscle,

umbilical cord, liver, placenta, skin, amniotic fluid, synovial membrane, and tooth root.

MSC have been intensely investigated for clinical applications within the last decades with a very strong record of safety and tolerability.

majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models.

This can be attributable to inconsistent

properties of MSC across studies as a result of variations in tissue source, donor variability, as well as isolation and manufacturing methodologies.

The generation of MSC from an iPSC source eliminates many of the sources of variability attributable to tissue derived MSC.

Sources of reduced variability include the use a single tissue source

and single donor as well as the ability to make larger cell banks due to the more extensive proliferation capacity of iMSC.

Moreover, development of iMSC products can leverage decades of valuable manufacturing, preclinical and clinical experience

Brooklyn plans to create “off-the-shelf” iMSC products in clinical indications that harness their anti-inflammatory and tumor homing properties.

Further, gene editing of iPSC can produce a stable source for iMSC that are endowed with

additional therapeutically beneficial properties that are not present in tissue derived MSC or native iMSC.

Bone Marrow Transplant and Inflammatory Diseases

Brooklyn is exploring the use of iMSC to address primary graft failure or poor graft function after bone marrow or hematopoietic stem cell transplantation, or BM/HSCT in addition to potential

applications in the prevention and/or treatment of graft vs host disease.

Preclinical studies will be conducted to demonstrate the ability of iMSC to target the bone marrow and influence the microenvironment.

In addition, we have assembled an

advisory board of world class experts in BM/HSCT to guide the clinical trial design and selection of clinical populations that are most likely to show benefit of a secondary transplant after treatment with iMSC.

Tumor Localized Delivery of Immune Stimulating Cytokines

The ability of MSC to migrate and navigate to sites of inflammation, including tumors, makes MSC attractive for delivery of oncology therapeutics.

We intend to use gene editing of iPSC to

produce a cell line with expression of the immune stimulatory cytokines, which then can be used to generate iMSC that express both IL-7 and IL-15.

Following systemic delivery of the gene edited iMSC, we believe that migration and homing to tumor

sites will result in a localized and more sustained delivery of these potent cytokines in the tumor microenvironment without producing the side effects that occur with high dose systemic administration of these cytokines.

Precision In vivo Genetic Medicines

We believe that the ability to engineer target site-specific DNA endonucleases with high fidelity (gene editing) has opened a new therapeutic arena for addressing the underlying genetic basis

Gene editing systems that possess both high specificity (low off-target editing) and high efficiency for on-target editing enable the in vivo use of the gene editing machinery to specifically modify patient DNA in target tissues and

thus address the genetic underpinnings of numerous disease states.

Brooklyn’s in-licensed technologies are being leveraged to develop genetic medicines that can achieve precision in vivo gene editing to address disorders that occur primarily as a

result of mutations in a single gene.

The initial disease and gene targets being pursued include familial transthyretin amyloidosis ( TTR gene mutations) and Stargardt disease ( ABC4A gene mutation).

Autologous and Allogeneic Cell Therapy

Cellular reprogramming refers to the process of generating pluripotent stem cells from non-pluripotent somatic cells (e.g., dermal fibroblasts obtained through a skin biopsy) by the forced

expression of key genes and factors important for maintaining the defining properties of pluripotent cells.

We believe the in-licensed technology for mRNA-based cellular reprogramming is highly efficient and safer than methods that utilize viral

vectors or plasmid DNA for expression of reprogramming factors because it eliminates the chance of DNA integration and potential for creating mutations in genomic DNA.

Also, our proprietary reprogramming process utilizes daily repeated

transfection of mRNA for expression of reprogramming factors and can achieve a rapid generation of iPSC clones (in 2 weeks) from patient tissue biopsy.

This rapid and efficient process therefore reduces the potential negative impact of low

quantity biopsy material and enhances reproducibility of autologous iPSC generation.

Furthermore, by delivering mRNA for a gene editing nuclease, genomic modifications, including correction of mutations, can be simultaneously performed thus

streamlining overall manufacturing time to produce gene-corrected autologous cells.

We expect that this approach, leveraging the proprietary in licensed technologies, can be employed to produce cell therapies addressing genetic diseases (e.g.,

sickle cell disease) of infectious diseases (e.g.

In addition, we have the potential to generate off-the-shelf (allogeneic) iPSC derived cell therapies for truly personalized cell therapy application in patients with genetic diseases.

Recent Developments

Listing on The Nasdaq Global Market

We transferred the listing of our common stock to The Nasdaq Global Market effective October 25, 2021, after voluntarily withdrawing the listing from the NYSE American stock exchange.

common stock continues to trade under the stock symbol “BTX.”

PIPE Transaction

On March 6, 2022, we entered into a Securities Purchase Agreement with an investor (the “PIPE Investor”) providing for the private placement (the “PIPE Transaction”) to the PIPE Investor of

approximately 6,857,000 units (the “Units”), each of which consisted of (i) one share of our common stock (or, in lieu thereof, one pre-funded warrant (the “Pre-Funded Warrants”) to purchase one share of common stock) and (ii) one warrant (the

“Common Warrants”) to purchase one share of common stock, for an aggregate purchase price of approximately $12.0 million.

The PIPE Transaction closed on March 9, 2022.

Each Pre-Funded Warrant has an exercise price of $0.005 per share of common stock, was immediately exercisable and may be exercised at any time and has no expiration date and is subject to

customary adjustments.

The Pre-Funded Warrants may not be exercised if the aggregate number of shares of common stock beneficially owned by the holder thereof would exceed 9.99% immediately after exercise thereof.

Each Common Warrant has an exercise price of $1.91 per share, becomes exercisable six months following the closing of the PIPE Transaction, expires five-and-one-half years from the date of

issuance, and is subject to customary adjustments.

The Common Warrants may not be exercised if the aggregate number of shares of common stock beneficially owned by the holder thereof would exceed 4.99% immediately after exercise thereof,

subject to increase to 9.99% at the option of the holder.

In connection with the PIPE Transaction, we and the PIPE Investor also entered into a registration rights agreement, dated March 6, 2022, pursuant to which we agreed to prepare and file a

registration statement with the Securities and Exchange Commission (the “SEC”) to register the resale of the shares of common stock included in the Units and the shares of common stock issuable upon exercise of the Pre-Funded Warrants and the

Common Warrants.

We agreed to use our best efforts to have such registration statement declared effective as promptly as possible after the filing thereof, subject to certain specified penalties if timely effectiveness is not achieved.

Purchase Agreements

On April 26, 2021, we and Lincoln Park Capital Fund, LLC, or Lincoln Park, executed a purchase agreement, or the First Purchase Agreement.

Pursuant to the First Purchase Agreement, we had the

right, but not the obligation, to sell to Lincoln Park, and Lincoln Park would be obligated to purchase, up to $20.0 million of shares of our common stock.

Sales of common stock by us were subject to certain limitations, and could occur from time

to time, at our sole discretion.

In consideration for Lincoln Park’s entry into the First Purchase Agreement, we issued Lincoln Park approximately 56,000 shares of common stock.

As of December 31, 2021, we had issued and sold to Lincoln Park

approximately 1,128,000 shares of common stock under the First Purchase Agreement for gross proceeds of $20.0 million, and no further shares may be sold to Lincoln Park under the First Purchase Agreement.

On May 26, 2021, we and Lincoln Park executed a second purchase agreement, or the Second Purchase Agreement, and together with the First Purchase Agreement, the Purchase

Pursuant to the Second Purchase Agreement, we have the right, but not the obligation, to sell to Lincoln Park, and Lincoln Park would be

obligated to purchase, up to $40.0 million of shares of our common stock.

Sales of common stock by us are subject to certain limitations, and may occur from time to time, at our sole discretion.

In consideration of Lincoln Park’s entry into the

Second Purchase Agreement, we issued to Lincoln Park 50,000 shares of common stock.

Under the Second Purchase Agreement, we may direct Lincoln Park to purchase up to 60,000 shares of common stock on any business day, which we refer to as a Regular Purchase, which amount may be

increased up to 120,000 shares based on the closing price of the common stock, provided that Lincoln Park’s maximum commitment in any single Regular Purchase may not exceed $2.0 million.

The purchase price per share for each such Regular Purchase

is based off of the common stock’s market immediately preceding the time of sale.

The Second Purchase Agreement also prohibits us from directing Lincoln Park to purchase any shares of common stock if those shares, when aggregated with all other shares of common stock then

beneficially owned by Lincoln Park and its affiliates, would result in Lincoln Park and its affiliates having beneficial ownership, at any single point in time, of more than 4.99% of the then total outstanding shares of common stock.

right to terminate the Second Purchase Agreement at any time, at no cost or penalty.

Actual sales of shares of common stock to Lincoln Park under the Second Purchase Agreements depend on a variety of factors to be determined by us from time to time, including, among others,

market conditions, the trading price of the common stock and determinations by us as to the appropriate sources of funding for us and our operations.

As of December 31, 2021, we had issued and sold approximately 2,424,000 shares of common stock under the Second Purchase Agreement for total gross proceeds of $34.1 million.

Pursuant to the

securities purchase agreement in respect of the PIPE Transaction, we are prohibited from issuing additional shares under the Second Purchase Agreement for a period of one -year immediately following the closing of the PIPE Transaction.

Acquisition of Novellus

On July 16, 2021, Brooklyn and its newly formed, wholly owned subsidiary Brooklyn Acquisition Sub, Inc.

entered into an agreement and plan of acquisition, or the Acquisition Agreement, with (a)

Novellus LLC, (b) Novellus, Inc., the sole equity holder of Novellus, Ltd.

and, prior to the closing under the Acquisition Agreement, a wholly owned subsidiary of Novellus, LLC, and (c) a seller representative.

Novellus, Ltd.

is a pre-clinical

stage biotechnology company organized under the laws of Ireland that is developing engineered cellular medicines using its licensed, patented non-immunogenic mRNA, high-specificity gene editing, mutation-free and footprint-free cell reprogramming

and serum-insensitive mRNA lipid delivery technologies.

The Acquisition closed contemporaneously with the execution and delivery of the Acquisition Agreement.

We delivered consideration for the Acquisition totaling approximately $124.0 million, which consisted of (a) $22.8 million in cash and (b) approximately 7,022,000 shares of common stock, which

under the terms of the Acquisition Agreement were valued at a total of $102.0 million, based on a price of $14.5253 per share.

We expect the Acquisition will advance our evolution into a platform company with a pipeline of next generation engineered cellular, gene editing and cytokine programs.

The completion of the

Acquisition relieves Brooklyn LLC from potential obligations to pay Novellus, Ltd.

certain upfront fees, clinical development milestone fees and post-registration royalties under the License Agreement.

The agreement with Factor under the License

Agreement, which grants Brooklyn LLC exclusive rights to develop certain next-generation mRNA gene editing and cell therapy products, remains unchanged.

License and Royalty Agreements

Cell and Gene Therapy

On April 26, 2021, Brooklyn LLC entered into an exclusive license agreement, or the License Agreement, with Novellus, Ltd.

and Factor, or the Licensors, to license the Licensors’ intellectual

property and mRNA cell reprogramming and gene editing technology for use in the development of certain cell-based therapies to be evaluated and developed for treating human diseases, including certain types of cancer, sickle cell disease, and

beta thalassemia.

Through the License Agreement, Brooklyn LLC acquired an exclusive worldwide license to develop and commercialize certain cell-based therapies to treat cancer and rare blood disorders, including sickle cell disease, based on

patented technology and know-how of Novellus, Ltd.

The License Agreement provides that Brooklyn LLC pay the Licensors a total of $4.0 million in connection with the execution of the License Agreement, all of which has been paid.

was obligated to pay to the Licensors additional fees of $5.0 million in October 2021 and $7.0 million in October 2022.

The completion of our July 16, 2021 acquisition of Novellus, Inc., the sole equity holder of Novellus, Ltd., relieves us from potential obligations to pay Novellus, Ltd.

certain upfront fees,

clinical development milestone fees and post-registration royalties under the License Agreement.

The agreements with Factor under the License Agreement remain unchanged.

Brooklyn LLC is obligated to pay Factor $2.5 million in October 2021, which

has been paid, and $3.5 million in October 2022.

Under the terms of the License Agreement, Brooklyn LLC is required to use commercially reasonably efforts to achieve certain delineated milestones, including specified clinical development and

regulatory milestones and specified commercialization milestones.

In general, upon its achievement of these milestones, Brooklyn LLC will be obligated, in the case of development and regulatory milestones, to make milestone payments to Licensor

in specified amounts and, in the case of commercialization milestones, to specified royalties with respect to product sales, sublicense fees or sales of pediatric review vouchers.

In the event Brooklyn LLC fails to timely achieve certain

delineated milestones, the Licensors may have the right to terminate the rights of Brooklyn LLC under provisions of the License Agreement relating to those milestones.

The Licensors are responsible for preparing, filing, prosecuting and maintaining all patent applications and patents under the License Agreement.

If, however, the Licensors determine not to

maintain a particular licensed patent or not to prepare, file and prosecute a licensed patent, Brooklyn LLC will have the right, but not the obligation, to assume those responsibilities in the territory at its expense.

Novellus, Ltd.

is a pre-clinical development, manufacturing, and technology licensing entity focused on engineered cellular medicines.

Novellus, Ltd.

has developed mRNA-based cell reprogramming

and gene editing technologies to create engineered cellular medicines.

The synthetic mRNA is non-immunogenic—it is capable of successfully evading the cellular innate immune system and then is capable of expressing high levels of proteins for

cell reprogramming and gene editing.

The mRNA may be formulated for injection into target tissues for cellular uptake and therapeutic treatment.

The synthetic mRNA technology may be used to edit gene mutations or expressed gene-editing proteins to treat genetic and rare diseases.

It may also be used to reprogram human non-pluripotent

cells into induced pluripotent stem cells )(iPSC).

The iPSC may then be differentiated into populations of varying therapeutic cell types.

The reprogramming technology offers a rapid and patient specific therapy using the engineered stem cells

created from iPSC that may avoid the cost, complexity and safety issues associated with viral vector gene editing approaches.

Novellus, Ltd.

also has licenses from Factor to use over 70 granted patents throughout the world covering synthetic mRNA, RNA-based gene editing, and RNA-based cell reprogramming, in addition

to specific patents covering methods for treating specific diseases.

There are also more than 60 pending patent applications throughout the world focused on these and other aspects of the technology.

The patent coverage includes granted patents

and pending patent applications in the United States, Europe, and Japan, along with other major life sciences markets.

Novellus, Ltd.

is required to use commercially reasonably efforts to achieve certain delineated milestones, including specified clinical development and regulatory milestones and specified

commercialization milestones.

In general, upon its achievement of these milestones, Novellus, Ltd.

will be obligated, in the case of development and regulatory milestones, to make milestone payments of up to $51 million in aggregate to Factor

and, in the case of commercialization milestones, specified royalties with respect to product sales, sublicense fees or sales of pediatric review vouchers.

In the event Novellus, Ltd.

fails to timely achieve certain delineated milestones,

Factor may have the right to terminate Novellus, Ltd.’s rights under provisions of the License Agreement relating to those milestones.

There can be no assurance that Brooklyn LLC can successfully develop and commercialize the technology licensed under the License Agreement.

Unless otherwise stated below, each royalty to be paid under these license and royalty agreements is payable until the last patent for IRX-2 expires and runs in perpetuity

unless earlier terminated pursuant to the terms described below.

There are no milestone payments due under any of these agreements.

License Agreement with the University of South Florida Research Association

On June 28, 2000, IRX Therapeutics, a predecessor of Brooklyn LLC, entered into a series of License Agreements (collectively, the “USF License Agreement”) with the University of South Florida

Research Association, Inc.

(“Research Association”).

Pursuant to the USF License Agreement, as amended, the Research Association licensed to IRX Therapeutics the exclusive worldwide rights to certain patents on IRX-2 in exchange for royalties

equal to 7% of the gross product sales of IRX-2 (as defined in the USF License Agreement).

The USF License Agreement was assigned to Brooklyn LLC in connection with the sale of the assets of IRX Therapeutics to Brooklyn in November 2018.

Research Association has the right to terminate the USF License Agreement (i) upon Brooklyn LLC’s entering into bankruptcy or insolvency on a voluntary or involuntary basis, (ii) upon the failure to pay royalties due and payable upon thirty days’

notice, or (iii) upon a material breach or default of the Agreement by Brooklyn LLC, unless such breach or default is cured within a thirty-day notice period.

Brooklyn may terminate the USF License Agreement for any reason upon six months’ notice

to the Research Association.

Royalty Agreement with certain former IRX Therapeutics investors

On May 1, 2012, IRX Therapeutics entered into a royalty agreement (the “IRX Investor Royalty Agreement”) with certain investors who participated in a financing transaction.

The IRX Investor

Royalty Agreement was assigned to Brooklyn LLC in November 2018 when Brooklyn LLC acquired the assets of IRX Therapeutics.

Pursuant to the IRX Investor Royalty Agreement, if and when Brooklyn LLC becomes obligated to pay royalties to the Research

Association under the USF License Agreement, it will pay an additional royalty of 1% of gross sales to an entity organized by the investors who participated in such financing transaction.

There are no termination provisions in the IRX Investor

Royalty Agreement.

Collaborator License Agreement

Effective June 28, 2018, IRX Therapeutics terminated its Research, Development and Option Facilitation Agreement (the “Termination Agreement”) and its Options Agreement with a collaborative

partner (the “Collaborator”), pursuant to a Termination Agreement.

In connection with the Termination Agreement, all of the rights granted to the Collaborator under the RDO and Option Agreements were terminated, and IRX Therapeutics had no

obligation to refund any payments received from the Collaborator.

The Termination Agreement was assigned to Brooklyn LLC in connection with the sale of the assets of IRX Therapeutics to Brooklyn in November 2018.

As consideration for entering into the Termination Agreement, the Collaborator will receive a royalty equal to 6% of revenues from the sale of IRX-2, for the period of time beginning with the

first sale of IRX-2 through the later of (i) the twelfth anniversary of the first sale of IRX-2, or (ii) the expiration of the last IRX patent or other exclusivity of IRX-2, all as more particularly set forth in the Termination Agreement.

party under the Termination Agreement may terminate the agreement (i) upon a material breach of the Termination Agreement by the other party that is not cured within sixty days (or thirty days if such breach is due to Brooklyn LLC’s non-payment

of royalties), or (ii) upon the other party entering into bankruptcy on a voluntary or involuntary basis where such petition is not dismissed, discharged, bonded or stayed within ninety days.

Investor Royalty Agreement

On November 6, 2018, Brooklyn LLC entered into a royalty agreement (the “Brooklyn Investor Royalty Agreement”) with Brooklyn Immunotherapeutics Investors LP (“Investors LP”) and Brooklyn

Immunotherapeutics Investors GP (“Investors GP”), which entities provided the financing required by Brooklyn LLC in connection with Brooklyn LLC’s acquisition of the assets of IRX Therapeutics.

Under the Brooklyn Investor Royalty Agreement,

Brooklyn LLC is required to pay compensatory royalties equal to 4% of gross sales of IRX-2 on an annual basis, 3% of which is to be paid to Investors LP and 1% of which is to be paid to Investors GP (all as more particularly set forth in the

Royalty Agreement).

This royalty continues in perpetuity.

In anticipation of the Merger, on March 22, 2021, Brooklyn LLC entered into an Amended and Restated Royalty Agreement and Distribution Agreement, or the Amended Royalty Agreement, with

Investors GP, Investors LP, and certain beneficial holders of GP and LP.

Pursuant to the Amended Royalty Agreement, among other things, we are required to pay compensatory royalties equal to 4% of net revenues of IRX-2, on an annual basis, of

which 3% is to be paid to certain beneficial holders of LP and 1% is to be paid to certain beneficial holders of GP.

The royalty continues in perpetuity.

The Royalty Agreement specifies royalty payments to certain beneficial holders, including:

Charles Cherington, one of our directors and stockholders has a right to receive 4.20% of the Specified Royalty;

entities affiliated with George P.

Denny III (Denny Family Partners II, LLC, the George P.

Denny Trust, and the R.

Breck Denny Trust), a former director and current stockholder have a right to receive a

total of 4.39% of the Specified Royalty;

an entity affiliated with Nicholas J.

Singer (PCI BI LLC), a former director and current stockholder, has a right to receive a total of 2.10% of the Specified Royalty

entities affiliated with Yiannis Monovoukas (The Yiannis Monovoukas Family 2013 Revocable Trust FBO Alexi Monovoukas, The Yiannis Monovoukas Family 2013 Revocable Trust FBO Aresti Monovoukas, and The

Yiannis Monovoukas Family 2013 Revocable Trust FBO Christian Monovoukas), a former director and stockholder have a right to receive a total of 1.40% of the Specified Royalty;

an entity affiliated with John D.

Halpern (The John D.

Halpern Revocable Trust), one of our stockholders, has a right to receive 3.50% of the Specified Royalty.

Patent Portfolio

As of April 12, 2022, we owned or controlled approximately 9 patent families filed in the United States and other major markets worldwide,

including 99 granted, 10 pending and 11 published patent applications, directed to novel compounds, formulations, methods of treatments and platform technologies.

Patent protection for IRX-2 includes:

Summary Description of Patent or Patent Application

United States or Foreign

Earliest Effective Date

of Patent Application

IRX-2 Modified Manufacturing Process

8,470,562), EP (BE, CH, DE, DK, ES, FI, FR, GB, IT, LI, NL, SW), AU, CA, JP, MX, TR

Method of Reversing Immune Suppression of Langerhans Cells

9,333,238 and 9,931,378), EP (BE, CH, DE, DK, ES, FI, FR, GB, LI, NL), AU, CA

6/8/2012 (No.

9,333,238), 4/13/2016 (No.

Method of Increasing Immunological Effect

7,993,660 and 8,591,956), EP (BE, CH, DE, DK, ES, FI, FR, GB, IT, LI, NL), AU, CA, JP

8/9/2011 (No.

7,993,660), 11/26/2013 (No.

Vaccine Immunotherapy

6,162,778, 9,492,517, 9,492,519, 9,539,320 and 9,566,331), EP (BE, CH, DE, DK, ES, FI, FR, GB, IT, LI, NL), AU, CA, HK, JP

7/24/2007 (No.

6,162,778), 10/8/2009 (No.

9,492,517), 11/15/2011 (No.

9,539,230), 2/20/2013 (No.

9,566,331), 7/12/2013 (No.

Immunotherapy for Reversing Immune Suppression

7,731,945), AU

Vaccine Immunotherapy for Immune Suppressed Patients

US (Patent Nos.

6,977,072, 7,153,499, 8,784,796, 9,789,172 and 9,789,173), CA, JP

10/26/2001 (No.

6,977,072), 5/5/2003 (No.

7,153,499), 7/12/2013 (No.

8,784,796), 6/4/2014 (Nos.

9,789,172 and 9,789,173)

Immunotherapy for Immune Suppressed Patients

EP (BE, CH, DE, ES, FR, GB, IT, NL, LI)

Composition for the Treatment of Advanced Prostate Cancer

Uses of PD-1/PD-L1 Inhibitors and/or CTLA-4 Inhibitors with a Biologic Containing Multiple Cytokine Components

AU, CA, EP, IL, JP, KR, NZ, PH, SG, US

BR, CN, EA, IN, MX, ZA

US – United States of America

EP – European Patent Convention

CH – Switzerland

GB – Great Britain

LI – Lichtenstein

NL – Netherlands

AU – Australia

CN – Peoples’ Republic of China

EA – Eurasian Patent Organization

HK – Hong Kong

KR – Republic of Korea (South Korea)

PH – Philippines

SG - Singapore

ZA – South Africa

Patent Families

Descriptions of our patent families with issued patents in the United States or European Union are as follows:

IRX-2 Modified Manufacturing Process - A method of making a primary cell derived biologic, including the steps of:

(a) removing contaminating cells from mononuclear cells (“MNCs”) by loading leukocytes onto

lymphocyte separation medium (“LSM”), and washing and centrifuging the medium with an automated cell processing and washing system;

(b) storing the MNCs overnight in a closed sterile bag system;

ciprofloxacin in a disposable cell culture system to produce cytokines;

(d) removing the mitogen from the mononuclear cells by filtering;

(e) incubating the filtered MNCs in a culture medium;

(f) producing a clarified supernatant by

filtering the MNCs from the culture medium;

(g) producing a chromatographed supernatant by removing DNA from the clarified supernatant by anion exchange chromatography;

and (h) removing viruses from the chromatographed supernatant by

filtering with dual 15 nanometer filters in series, thereby producing a primary cell derived biologic, wherein the primary cell derived biologic comprises IL-1.beta., IL-2, and IFN-.gamma.

Method of Reversing Immune Suppression of Langerhans Cells - A method of treating human papillomavirus (“HPV”), by administering a therapeutically effective amount of a primary cell-derived biologic to a

patient infected with HPV and inducing an immune response to HPV.

A method of overcoming HPV-induced immune suppression of Langerhans cells (“LC”), by administering a therapeutically effective amount of a primary cell-derived biologic to

a patient infected with HPV and activating LC.

A method of increasing LC migration towards lymph nodes, by administering a therapeutically effective amount of a primary cell-derived biologic to a patient infected with HPV, activating LC,

and inducing LC migration towards lymph nodes.

A method of generating immunity against HPV, by administering an effective amount of a primary cell derived biologic to a patient infected with HPV, generating immunity against HPV, and

preventing new lesions from developing.

Method of Increasing Immunological Effect - A method of increasing immunological effect in a patient by administering an effective amount of a primary cell derived biologic to the patient, inducing immune

production, blocking immune destruction, and increasing immunological effect in the patient.

Methods of treating an immune target, treating a tumor, immune prophylaxis, and preventing tumor escape.

Vaccine Immunotherapy/Composition for the Treatment of Advanced Prostate Cancer – A method providing compositions and methods of immunotherapy to treat cancer or other antigen-producing diseases or lesions.

According to one embodiment of the invention, a composition is provided for eliciting an immune response to at least one antigen in a patient having an antigen-producing disease or lesion, the composition comprising an effective amount of

a cytokine mixture, preferably comprising IL-1, IL-2, IL-6, IL-8, IFN-gamma.

(gamma) and TNF- alpha (alpha).

The cytokine mixture acts as an adjuvant with the antigen associated with the antigen-producing disease or lesion to enhance the

immune response of the patient to the antigen.

Methods are therefore also provided for eliciting an immune response to at least one antigen in a patient having an antigen-producing disease or lesion utilizing the cytokine mixture of the

The compositions and methods are useful in the treatment of antigen-producing diseases such as cancer, infectious diseases or persistent lesions.

Immunotherapy for Reversing Immune Suppression - A method for overcoming immune suppression including the steps of inducing production of naïve T-cells and restoring T cell immunity.

of vaccine immunotherapy includes the steps of inducing production of naïve T cells and exposing the naïve T cells to endogenous or exogenous antigens at an appropriate site.

Additionally, a method for unblocking immunization at a regional lymph

node includes the steps of promoting differentiation and maturation of immature dendritic cells, thus, for example, exposing tumor peptides to T cells to gain immunization of the T cells.

Further, a method of treating cancer and other persistent

lesions includes the steps of administering an effective amount of a natural cytokine mixtures an adjuvant to endogenous or exogenous administered antigen to the cancer or other persistent lesions;

preferably the natural cytokine mixture is

administered with thymosin.

Vaccine Immunotherapy for Immune Suppressed Patients - A method for overcoming mild to moderate immune suppression includes the steps of inducing production of naive T-cells and restoring T-cell immunity.

method of vaccine immunotherapy includes the steps of inducing production of naive T-cells and exposing the naive T-cells to endogenous or exogenous antigens at an appropriate site.

Additionally, a method for unblocking immunization at a

regional lymph node includes the steps of promoting differentiation and maturation of immature dendritic cells at a regional lymph node and allowing presentation of processed peptides by resulting mature dendritic cells, thus, for

example, exposing tumor peptides to T-cells to gain immunization of the T-cells.

Further, a method of treating cancer and other persistent lesions includes the steps of administering an effective amount of a natural cytokine mixture as an

adjuvant to endogenous or exogenous administered antigen to the cancer or other persistent lesions.

Immunotherapy for Immune Suppressed Patients – A method providing compositions of a natural cytokine mixture (“NCM”) for treating a cellular immunodeficiency characterized by T lymphocytopenia, one or more

dendritic cell functional defects such as those associated with lymph node sinus histiocytosis, and/or one or more monocyte functional defects such as those associated with a negative skin test to NCM.

The invention includes methods of

treating these cellular immunodeficiences using the NCM of the invention.

The compositions and methods are useful in the treatment of diseases associated with cellular immunodeficiencies such as cancer.

Also provided are compositions and

methods for reversing tumor-induced immune suppression comprising a chemical inhibitor and a non-steroidal anti-inflammatory drug (“NSAID”).

The invention also provides a diagnostic skin test comprising NCM for predicting treatment

outcome in cancer patients.

Patent Term and Term Extensions

Individual patents have terms for varying periods depending on the date of filing of the patent application or the date of patent issuance and the legal term of patents in the countries in

which they are obtained.

Generally, utility patents issued for applications filed in the United States and the European Union are granted a term of 20 years from the earliest effective filing date of a non-provisional patent application.

addition, in certain instances, a patent term can be extended to recapture a portion of the U.S.

Patent and Trademark Office, or the USPTO, delay in issuing the patent as well as a portion of the term effectively lost as a result of the FDA

regulatory review period.

However, as to the FDA component, the restoration period cannot be longer than five years and the restoration period cannot extend the patent term beyond 14 years from FDA approval.

The duration of foreign patents varies

in accordance with provisions of applicable local law, but typically are also 20 years from the earliest effective filing date.

All taxes or annuities for a patent, as required by the USPTO and various foreign jurisdictions, must be timely paid

in order for the patent to remain in force during this period of time.

The actual protection afforded by a patent may vary on a product-by-product basis, from country to country, and can depend upon many factors, including the type of patent, the scope of its

coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent.

Our patents and patent applications may be subject to procedural or legal challenges by others.

We may be unable to obtain, maintain and protect the intellectual property rights necessary to

conduct our business, and we may be subject to claims that we infringe or otherwise violate the intellectual property rights of others, which could materially harm our business.

For more information, see the section titled “Risk Factors-Risks

Related to Our Intellectual Property.”

Supply and Manufacturing

Brooklyn has considerable experience in manufacturing the investigational active pharmaceutical ingredient (“API”) currently in the clinic.

In recent years, we maintained internal API

manufacturing capabilities.

We are currently investigating the option of outsourcing API manufacturing to an experienced contract manufacturing organization (“CMO”), as we had historically done, to mitigate the overhead costs of internal

manufacturing and leverage process development expertise to streamline and eliminate some of the more manual processes, thereby reducing risk of product microbial contamination.

The CMO selected will have the capability to produce high quality

product to meet both the investigational and anticipated commercial demands.

There will be technology transfer and process validation costs, which will be carefully considered in any decision.

We have established long-standing contract

manufacturing relationships for fill/finish and packaging of the clinical supplies of IRX-2.

As with any supply program, obtaining raw materials of the correct quality, and the performance of our contract manufacturing sites cannot be

Due to the current demand for CMO services and supply chain issues in the COVID-19 pandemic environment we cannot ensure that we will be successful in obtaining such raw materials on terms acceptable to us, if at all.

We expect to similarly rely on contract manufacturing relationships for any products that we may in-license or acquire in the future.

However, there can be no assurance that we will be able to

successfully contract with such manufacturers on terms acceptable to us, or at all.

Contract manufacturers are subject to ongoing periodic and unannounced inspections by the FDA, the Drug Enforcement Administration (“DEA”) and corresponding state agencies to ensure strict

compliance with current good manufacturing practices (“cGMPs”) and other state and federal regulations.

Our contractors, if any, in Europe face similar challenges from the numerous European Union and member state regulatory agencies and

authorized bodies.

We do not have control over third-party manufacturers’ compliance with these regulations and standards, other than through contractual obligations.

If our contractors are deemed out of compliance with cGMPs, product recalls

could result, inventory could be destroyed, production could be stopped, and supplies could be delayed or otherwise disrupted, which could have a materially adverse effect on our business.

If we need to change manufacturers after commercialization, the FDA and corresponding foreign regulatory agencies must approve these new manufacturers in advance, which will involve testing and

additional inspections and associated regulatory submissions to ensure compliance with FDA regulations and standards, which collectively may result in significant lead times, delay and cost.

Furthermore, switching manufacturers may be difficult

because the number of potential manufacturers is limited.

It may be difficult or impossible for us to find a replacement manufacturer quickly or on terms acceptable to us, or at all.

Regulatory Matters

Government regulation and product approval

Government authorities in the United States, at the federal, state and local level, and in other countries extensively regulate, among other things, the research, development, testing,

manufacture, labeling, record-keeping, promotion, storage, advertising, distribution, marketing and export and import of products such as those we are developing.

Drugs and biologics must be approved by the FDA through the New Drug Application,

(NDA) process or the Biologic License Application (BLA) process before they may be legally marketed in the United States.

Henceforth, we will use the term “marketing application” or MA to apply to both.

There are two centers within the FDA that are responsible for the review and approval of drug marketing applications and general regulatory oversight:

the Center for Drug Evaluation and

Research, or CDER, and the Center for Biologics Evaluation and Research, or CBER.

While all conventional drug products are regulated by CDER, biologic products can be regulated by either CDER or CBER, depending on the product’s classification.

The majority of BLA submissions are assigned to CBER;

however, BLAs for certain biologic product categories are reviewed by CDER.

These product categories include monoclonal antibodies for in

vivo use, most proteins for therapeutic use, and categories such as cytokines, enzymes, and other novel proteins.

Based on this, it is likely that a BLA submission for IRX-2 would fall under the jurisdiction of CDER.

Regardless of the category,

NDAs for all drug products fall under the jurisdiction of CDER.

In the United States, drugs are subject to rigorous regulation by the FDA under the federal Food, Drug, and Cosmetic Act, or FDCA, and implementing regulations, and biologics under the FDCA,

the Public Health Services Act (PHSA), and their implementing regulations.

Additionally, drugs and biologics are subject to other federal and state statutes.

The process of obtaining regulatory approvals and the subsequent compliance with

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

Failure to comply with the applicable United States 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 the FDA’s refusal to approve pending applications, license suspension or revocation,

withdrawal of an approval, a clinical hold, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties or criminal prosecution.

Any agency or judicial

enforcement action could have a material adverse effect on us.

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

completion of pre-clinical laboratory tests, animal studies and formulation studies according to the FDA’s good laboratory practice, or GLP, regulations;

submission of an investigational new drug application, or IND, which must become effective before human clinical trials may begin and which must include approval by an institutional review board, or IRB, at

each clinical site before the trials are initiated;

performance of adequate and well-controlled human clinical trials to establish the safety and efficacy of the proposed drug for its intended use conducted in compliance with federal regulations and good

clinical practice, or GCP, an international standard meant to protect the rights and health of human clinical trial subjects and to define the roles of clinical trial sponsors, administrators, and monitors;

submission to, and acceptance by, the FDA of a MA;

satisfactory completion of an FDA inspection of our manufacturing facility or other facilities at which the drug or biologic is produced to assess compliance with current good manufacturing practice, or

cGMP, regulations to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

potential FDA audit of the non-clinical and clinical trial sites that generated the data in support of the MA:

FDA review and approval of the MA.

The testing and approval process require substantial time, effort and financial resources, and the receipt and timing of any approval is uncertain.

United States drug development process

Once a pharmaceutical candidate is identified for development it enters the pre-clinical testing stage.

Pre-clinical tests include laboratory evaluations of product chemistry, toxicity and

formulation, as well as animal studies.

Prior to beginning human clinical trials, a sponsor must submit an Investigational New Drug Application (“IND”) to the FDA, which includes the results of the pre-clinical tests, together with manufacturing

information and analytical data.

Some pre-clinical or non-clinical testing may continue even after the IND is submitted.

In addition to including the results of the pre-clinical studies, the IND will also include a protocol detailing, among other

things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated, if the trial lends itself to an efficacy evaluation.

The IND automatically becomes effective 30 days

after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions about the conduct of the trial.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can

The FDA may, at any time, impose a clinical hold on ongoing clinical trials.

If the FDA imposes a clinical hold, clinical trials cannot commence or recommence without FDA authorization and then only under terms authorized by the FDA.

Clinical trials involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of one or more qualified investigators in accordance with

federal regulations and GCP.

Clinical trials must be conducted under protocols detailing the objectives of the trial and the safety and effectiveness criteria to be evaluated.

Each protocol must be submitted to the FDA as

part of the IND.

Further, an Institutional Review Board, or IRB, affiliated with each institution participating in the clinical trial must review and approve each protocol before any clinical trial commences at that institution.

subjects must provide informed consent, and informed consent information must be submitted to the IRB for approval prior to initiation of the trial.

Progress reports detailing the results of the clinical trials must be submitted at least annually

to the FDA and more frequently if adverse events or other certain types of other changes occur.

Human clinical trials are typically conducted in three phases.

A fourth, or post-approval, phase may include additional clinical studies.

These phases generally include the following, and may

be sequential, or may overlap or be combined:

Phase 1 clinical trials involve the initial introduction of the drug or biologic into human subjects.

These studies are designed to determine the safety of usually single doses of the compound and determine

any dose limiting intolerance, as well as evidence of the metabolism and pharmacokinetics of the drug in humans.

For some products for severe or life-threatening diseases, especially if the product may be too toxic to administer to

healthy humans, the initial clinical trials may be conducted in individuals having a specific disease for which use the tested product is indicated.

Phase 2 clinical trials usually involve studies in a limited patient population to evaluate the safety and efficacy of the drug or biologic for specific, targeted indications, to determine dosage tolerance

and optimal dosage, and to identify possible adverse effects and safety risks.

In Phase 3, if a compound is found to be potentially effective and to have an acceptable safety profile in Phase 2 (or occasionally Phase 1) studies, the Phase 3 studies will be conducted to further confirm

clinical efficacy, optimal dosage and safety within an expanded population which may involve geographically diverse clinical trial sites.

Generally, but not always, two adequate and well-controlled Phase 3 clinical trials are required by

the FDA for approval of a marketing application.

Phase 4 clinical trials are studies required of or agreed to by a sponsor that are conducted after the FDA has approved a product for marketing.

These studies are used to gain additional experience from the

treatment of patients in the intended therapeutic indication and to document a clinical benefit in the case of drugs approved under accelerated approval regulations.

If the FDA approves a product while a company has ongoing clinical

trials that were not necessary for approval, a company may be able to use the data from these clinical trials to meet all or part of any Phase 4 clinical trial requirement.

Failure to promptly conduct Phase 4 clinical trials where

necessary could result in withdrawal of approval for products approved under accelerated approval regulations.

While Phase 1, Phase 2, and Phase 3 studies are generally required for approval of a marketing application, certain drugs and biologics may not require one or more steps in the process

depending on other testing and the situation involved.

Additionally, the FDA, an IRB, or the sponsor may stop testing at any time if results show patients being exposed to unnecessary health risks or overly dangerous side effects.

initiation of a clinical trial or at any time during the conduct of studies with human subjects, the FDA may place a study on clinical hold where patients may not be enrolled until questions around potential safety issues with investigational

products are addressed.

In addition, the manufacturer of an investigational drug in a Phase 2 or Phase 3 clinical trial for a serious or life-threatening disease is required to make available, such as by posting on

its website, its policy on evaluating and responding to requests for expanded access to such investigational drug.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the mechanism of action and physical characteristics of

the drug and finalize a process for manufacturing the product in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of the product and, among other requirements, the manufacturer

must develop methods for testing the identity, strength, quality, potency, and purity of the final product.

Additionally, appropriate packaging must be selected and validated, and stability studies must be conducted to demonstrate that the

product does not undergo unacceptable deterioration over its shelf life.

United States drug review and approval process

Following completion of clinical studies, the results are evaluated and, depending on the outcome, submitted to the FDA in the form of an NDA or BLA in order to obtain FDA approval of the

product and authorization to commence commercial marketing.

In responding to an NDA, the FDA may require additional testing or information, may require that the product labeling be modified, may impose a post-approval study and other commitments

or reporting requirements or other restrictions on product distribution, or may deny the application.

The timing of final FDA review and action varies greatly but can take years in some cases and may involve the input of an FDA advisory

committee of outside experts.

Product sales in the United States may commence only when an NDA or BLA is approved.

FDA approval of a marketing application is required before marketing of the product may begin in the United States.

The MA must include the results of product development, pre-clinical studies

and clinical studies, together with other detailed information, including information on the chemistry, manufacture and controls utilized in manufacture of the product.

In addition, a MA must also demonstrate purity, specifically in terms of

showing that the final product does not contain extraneous material.

The FDA has 60 days from its receipt of the MA to review the application to ensure that it is sufficiently complete for substantive review before accepting it for filing.

FDA may request additional information rather than accept an MA for filing.

In this event, the MA must be resubmitted with the additional information.

The resubmitted application also is subject to review before the FDA accepts it for filing.

Once the submission is accepted for filing, the FDA begins an in-depth substantive review.

The submission of an MA is also subject to the payment of a substantial application fee (for FDA fiscal year 2022 this fee may exceed 3 million dollars,

although a waiver of such fee may be obtained under certain limited circumstances, including when the drug that is subject of the application has received Orphan Drug Designation for the indication sought).

Further, the sponsor of an approved MA

is subject to an annual program fee, which for FDA fiscal year 2022 is $369,413 per prescription drug product.

User fees typically increase annually.

The approval process is lengthy and complex, and the FDA may refuse to approve an MA if the

applicable regulatory criteria are not satisfied or may require additional clinical or other data and information.

Even if such data and information is submitted, the FDA may ultimately decide that the NDA or BLA does not satisfy the criteria for

The FDA may also refer applications for novel drug products or drug products which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review,

evaluation and a recommendation as to whether the application should be approved.

The FDA is not bound by the recommendation of an advisory committee.

The FDA reviews an application to determine, among other things, whether a product is safe and

effective for its intended use.

Before approving an MA, the FDA will inspect the facility or facilities where the product is manufactured to determine whether its manufacturing is cGMP–compliant to assure and preserve the product’s identity,

potency, quality, purity and stability.

If the FDA’s evaluation of the marketing submission or manufacturing facilities is not favorable, the FDA will issue a complete response letter.

The complete response letter outlines the

deficiencies in the submission and often requires additional testing or information in order for the FDA to reconsider the application.

Even after submitting this additional information, the FDA ultimately may decide that the application does not

satisfy the regulatory criteria for approval.

With limited exceptions, the FDA may withhold approval of a MA regardless of prior advice it may have provided or commitments it may have made to the sponsor.

Once an MA is approved, changes to the conditions of approval, including additional indications, are made by the submission of a supplement to the MA The supplemental NDA, or sNDA, or the

supplemental BLA, or sBLA must contain all of the information necessary to support the change.

In the case of a new indication, that information usually consists of at least one clinical trial, and often more.

Like an MA, FDA determines whether

the supplemental application is sufficiently complete to permit review before it is filed.

FDA then reviews the supplemental application.

The FDA can either approve or issue a complete response letter outlining the deficiencies.

Manufacturing Readiness

As part of the approval process, the FDA must inspect and approve each manufacturing facility.

Among the conditions of approval is the requirement that a manufacturer’s quality control and

manufacturing procedures conform to cGMP.

Manufacturers must expend significant time, money and effort to ensure continued compliance, and the FDA conducts periodic inspections to verify compliance.

If we, or our contract manufacturers, fail to

comply or cannot remedy regulator identified deficiencies, then we may be prohibited from marketing product.

If the FDA grants approval, the approval will be limited to those conditions and patient populations for which the product is safe and effective, as demonstrated through clinical studies.

Further, a product may be marketed only in those dosage forms and for those indications approved in the MA.

Certain changes to an approved MA, including, with certain exceptions, any significant changes to labeling, require approval of a

supplemental application before the drug may be marketed as changed.

Any products that we manufacture or distribute pursuant to FDA approvals are subject to continuing monitoring and regulation by the FDA, including compliance with cGMP and the

reporting of adverse experiences with the drugs.

The nature of marketing claims that the FDA will permit us to make in the labeling and advertising of our products will generally be limited to those specified in FDA approved labeling, and the

advertising of our products will be subject to comprehensive monitoring and regulation by the FDA.

Products whose review was accelerated may carry additional restrictions on marketing activities, including the requirement that all promotional

materials are pre-submitted to the FDA.

Claims exceeding those contained in approved labeling will constitute a violation of the FDCA.

Violations of the FDCA or regulatory requirements at any time during the product development process, approval

process, or marketing and sale following approval may result in agency enforcement actions, including corrective advertising, cessation of violative promotion, withdrawal of approval, recall, seizure of products, warning letters, injunctions,

fines and/or civil or criminal penalties.

Any agency enforcement action could have a material adverse effect on our business.

Failure to comply with applicable federal, state and foreign laws and regulations would likely have a material adverse effect on our business.

In addition, federal, state and foreign laws and

regulations regarding the manufacture and sale of new drugs are subject to future changes.

Post-approval requirements and consideration

Once a MA is approved, a product will be subject to certain post-approval requirements.

For instance, the FDA closely regulates the post-approval marketing and promotion of drugs and biologics,

including standards and regulations for direct-to-consumer advertising, off-label promotion, industry-sponsored scientific and educational activities and promotional activities involving the internet.

As a condition of MA approval, the FDA may

also require a risk evaluation and mitigation strategy, or REMS, to help ensure that the benefits of the drug or biologic outweigh the potential risks.

REMS can include medication guides, communication plans for the healthcare professionals, and

other Elements to Assure Safe Use, or ETASU.

ETASU can include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient

The requirement for a REMS can materially affect the potential market and profitability of the drug or biologic.

Drugs and biologics may be marketed only for the approved indications and in accordance with the provisions of the approved labeling.

Changes to some of the conditions established in an

approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new MA supplement before the change can be implemented.

An MA supplement for a new indication

typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing MA supplements as it does in reviewing MAs.

Adverse event reporting and submission of periodic reports is required following FDA approval of an MA.

The FDA also may require post-marketing testing, known as Phase 4 testing, and

surveillance to monitor the effects of an approved product or place conditions on an approval that could restrict the distribution or use of the product.

In addition, quality control as well as drug manufacture, packaging, and labeling procedures

must continue to conform to cGMPs after approval.

Drug and biologic manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced

inspections by the FDA during which the agency inspects manufacturing facilities to assess compliance with cGMPs.

Accordingly, manufacturers must continue to expend time, money and effort in the areas of production and quality control to maintain

compliance with cGMPs.

Regulatory authorities may withdraw product approvals or request product recalls if a company fails to comply with regulatory standards, if it encounters problems following initial marketing, or if previously unrecognized

problems are subsequently discovered.

Foreign regulatory requirements

In addition to regulation by the FDA and certain state regulatory agencies, we are also subject to a variety of foreign regulations governing clinical trials and the marketing of other

Outside of the United States, our ability to market a product depends upon receiving a marketing authorization from the appropriate regulatory agencies.

The requirements governing the conduct of clinical trials, marketing authorization,

pricing and reimbursement vary widely from country to country.

In any country, however, we will only be permitted to commercialize our products if the appropriate regulatory agency is satisfied that we have presented adequate evidence of safety,

quality and efficacy.

Whether or not FDA approval has been obtained, approval of a product by the comparable regulatory authorities of foreign countries must be obtained prior to the commencement of marketing of the product in those countries.

The regulatory approval and oversight process in other countries includes all of the risks associated with regulation by the FDA and certain state regulatory agencies as described above.

Under the European Union regulatory system, applications for drug approval may be submitted either in a centralized or decentralized manner.

Under the centralized procedure, a single

application to the European Medicines Agency may lead to an approval granted by the European Commission which permits marketing of the product throughout the European Union.

The decentralized procedure provides for mutual recognition of

nationally approved decisions and is used for products that do not comply with requirements for the centralized procedure.

Under the decentralized procedure, the holders of national marketing authorization in one of the countries within the

European Union may submit further applications to other countries within the European Union, who will be requested to recognize the original authorization based on an assessment report provided by the country in which marketing authorization is

Pharmaceutical pricing and reimbursement

In both United States and foreign markets, our ability to commercialize our products successfully, and to attract commercialization partners for our products, depends in significant part on the

availability of adequate financial coverage and reimbursement from third-party payors, including, in the United States, governmental payors such as Medicare and Medicaid, managed care organizations, private commercial health insurers and pharmacy

benefit managers, or PBMs.

Third party payors are increasingly challenging the prices charged for medicines and examining their cost effectiveness, in addition to their safety and efficacy.

We may need to conduct expensive pharmacoeconomic or

other studies in order to further demonstrate the value of our products.

Even with the availability of such studies, our products may be considered less safe, less effective or less cost-effective than alternative products, and third-party payors

may not provide coverage and reimbursement for our product candidates, in whole or in part.

Political, economic and regulatory influences are subjecting the health care industry in the United States to fundamental changes.

There have been, and we expect there will continue to be,

legislative and regulatory proposals to change the healthcare system in ways that could significantly affect our business, including the Patient Protection and Affordable Care Act of 2010 (the “Affordable Care Act”).

We anticipate that in the United States, Congress, state legislatures, and private sector entities will continue to consider and may adopt healthcare policies intended to curb rising healthcare

These cost containment measures could include:

controls on government-funded reimbursement for drugs;

mandatory rebates or additional charges to manufacturers for their products to be covered on Medicare Part D formularies;

controls on healthcare providers;

controls on pricing of pharmaceutical products, including the possible reference of the pricing of United States drugs to non-United States drug pricing for the same product;

challenges to the pricing of drugs or limits or prohibitions on reimbursement for specific products through other means;

reform of drug importation laws;

entering into contractual agreements with payors;

expansion of use of managed-care systems in which healthcare providers contract to provide comprehensive healthcare for a fixed cost per person

We are unable to predict what additional legislation, regulations or policies, if any, relating to the healthcare industry or third-party coverage and reimbursement may be enacted in the future

or what effect such legislation, regulations or policies would have on our business.

Any cost containment measures, including those listed above, or other healthcare system reforms that are adopted may have a material adverse effect on our

business prospects.

Further, the pricing of pharmaceutical products generally, and particularly the pricing of orphan drugs, has recently received scrutiny from the press and from members of Congress in both

Some members of the medical community have also made statements in the press on the pricing of orphan drugs.

The impact of this scrutiny on the pricing of orphan drugs and other pharmaceutical products generally cannot be determined with

any certainty at this time.

The Biologics Price Competition and Innovation Act of 2009, which was included in the Affordable Care Act, authorized the FDA to approve similar versions of innovative biologics, commonly known

as biosimilars.

Under the Affordable Care Act, a manufacturer may submit an application for licensure of a biologic product that is “biosimilar to” or “interchangeable with” a previously approved biologic product or “reference product.”

Manufacturers may not submit an application for a biosimilar to the FDA until four years following approval of the reference product, and the FDA may not approve a biosimilar product until 12 years from the date on which the reference product was

Even if IRX-2 or any other biologic product we may acquire or in-license, if approved, are deemed to be reference products eligible for exclusivity, another company could market a competing version of that product if the FDA approves a

full BLA for such product containing the sponsor’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product.

Orphan Drug Exclusivity

Some jurisdictions, including the United States and Europe, may designate drugs or biologic products for relatively small patient populations as orphan drugs.

Under the Orphan Drug Act of 1983

(ODA), the FDA may grant orphan drug designation to drugs or biologic products intended to treat a rare disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States

and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug for this type of disease or condition will be recovered from sales in the United States for that drug.

In the United

States, orphan drug designation must be requested before submitting an application for marketing approval.

An orphan drug designation does not shorten the duration of the regulatory review and approval process.

The grant of an orphan drug

designation request does not alter the standard regulatory requirements and process for obtaining marketing approval.

Safety and efficacy of a product candidate must be established through adequate and well-controlled studies.

If a product which

has been granted orphan drug designation subsequently receives the first FDA approval for the indication for which it has such designation, the product is entitled to an orphan drug exclusivity period, which means the FDA may not approve any

other application to market the same drug for the same disease or condition for a period of seven years, except in limited circumstances, such as where an alternative product demonstrates clinical superiority to the product with orphan

In addition, holders of exclusivity for orphan drugs are expected to assure the availability of sufficient quantities of their orphan drugs to meet the needs of patients.

Failure to do so could result in the withdrawal of marketing

exclusivity for the drug.

The orphan drug exclusivity contained in the ODA has been the subject of recent scrutiny from the press, from some members of Congress and from some in the medical community.

There can be no

assurance that the exclusivity granted in ODA to orphan drugs approved by the FDA will not be modified in the future, and as to how any such change might affect our products.

The European Orphan Drug Regulation is considered for drugs intended to diagnose, prevent or treat a life-threatening or very serious condition afflicting five or fewer per 10,000 people in the

EU, including compounds that for serious and chronic conditions would likely not be marketed without incentives due to low market return on the sponsor’s development investment.

The medicinal product considered should be of significant benefit to

those affected by the condition.

Benefits of being granted Orphan Medicinal Product Designation are significant, including ten years of marketing exclusivity and a potential two-year extension.

The EU Community and Member States may not accept or

grant for ten years a new marketing authorization or application for another drug for the same therapeutic indication as the orphan drug, although the ten-year period can be reduced to six years if, after the end of the fifth year, available

evidence establishes that the product is sufficiently profitable not to justify maintenance of the marketing exclusivity.

A supplementary protection certificate may extend the protection six months beyond patent expiration if that is later than

the orphan drug exclusivity period.

To apply for the supplementary protection, a pediatric investigation plan, or PIP, must be included in the market application.

In Europe all drugs now seeking marketing authorization need to have a PIP agreed

with the European Medicines Agency (EMA) before it can be approved, even if it is a drug being developed specifically for a pediatric indication.

If a product is developed solely for use in the pediatric population, then a Pediatric Use Marketing

Authorization, or PUMA, may provide eight years of data exclusivity and ten years of marketing exclusivity.

Fast Track Designation and Accelerated Approval

The FDA is required to facilitate the development, and expedite the review, of drugs or biologics that are intended for the treatment of a serious or life-threatening disease or condition for

which there is no effective treatment and which demonstrate the potential to address unmet medical needs for the condition.

Under the fast-track program, the sponsor of a new product candidate may request that FDA designate the product candidate

for a specific indication as a fast-track drug concurrent with, or after, the filing of the IND for the product candidate.

FDA must determine if the product qualifies for fast-track designation within 60 days of receipt of the sponsor’s request.

Under the fast track program and FDA’s accelerated approval regulations, FDA may approve a product for a serious or life-threatening illness that provides meaningful therapeutic benefit to

patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to

predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

In clinical trials, a surrogate endpoint is a measurement of laboratory or clinical signs of a disease or condition that substitutes for a direct measurement of how a patient feels, functions,

Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints.

A product approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of Phase 4 or

post-approval clinical trials to confirm the effect on the clinical endpoint.

Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, will allow FDA to withdraw the product from the market

on an expedited basis.

All promotional materials for products approved under accelerated regulations are subject to prior review by FDA.

In addition to other benefits such as the ability to use surrogate endpoints and engage in more frequent interactions with FDA, FDA may initiate review of sections of a fast-track drug’s MA

before the application is complete.

This rolling review is available if the applicant provides, and FDA approves, a schedule for the submission of the remaining information and the applicant pays applicable user fees.

However, FDA’s time period

goal for reviewing an application does not begin until the last section of the MA is submitted.

Additionally, the fast-track designation may be withdrawn by the FDA if they believe that the designation is no longer supported by data emerging in

the clinical trial process.

Priority Review

Under FDA policies, a product candidate is eligible for priority review, or review within a six to eight-month time frame from the time a complete MA is submitted, if the product candidate is

intended for the treatment, diagnosis, or prevention of a serious or life-threatening condition, demonstrates the potential to address an unmet medical need, or provides a significant improvement compared to marketed drugs.

Disclosure of clinical trial information

Sponsors of clinical trials of FDA-regulated products, including drugs, are required to register and disclose certain clinical trial information.

Information related to the product, patient

population, phase of investigation, study sites and investigators, and other aspects of the clinical trial is then made public as part of the registration.

Sponsors are also obligated to disclose the results of their clinical trials after

Disclosure of results of these trials can be delayed in certain circumstances for up to two years after the date of completion of the clinical trial.

Competitors may use this publicly available information to gain knowledge regarding

the progress of development programs.

Finally, there can be no assurance that fast track designation will result in a faster review process.

Anti-Kickback, False Claims Laws, Stark Law & the Prescription Drug Marketing Act

In addition to FDA restrictions on marketing of pharmaceutical products, other state and federal laws have been applied to restrict certain marketing practices in the pharmaceutical industry in

recent years.

These laws include anti-kickback prohibition, statutes and false claims statutes.

The federal healthcare program Anti-Kickback Statute, or Anti-Kickback Statute, prohibits, among other things, knowingly and willfully offering,

paying, soliciting or receiving remuneration to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any healthcare item or service reimbursable under Medicare, Medicaid or other federally

financed healthcare programs.

This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and patients, prescribers, purchasers and formulary managers on the other.

Violations of the

Anti-Kickback Statute are punishable by imprisonment, criminal fines, civil monetary penalties, and exclusion from participation in federal healthcare programs.

Although there are a number of statutory exceptions and regulatory safe harbors

protecting certain common activities from prosecution or other regulatory sanctions, the exceptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases or recommendations may be

subject to scrutiny if they do not qualify for an exemption or safe harbor.

Federal false claims laws prohibit, among other things, any person from knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly

making, or causing to be made, a false statement to have a false claim paid.

Recently, several pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly inflating drug prices they report to pricing

services, which in turn were used by the government to set Medicare and Medicaid reimbursement rates, and for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product.

addition, certain marketing practices, including off-label promotion, may also violate false claims laws.

The majority of states also have statutes or regulations similar to the Anti-Kickback Statute and false claims laws, which apply to items

and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payer.

Federal law includes a provision commonly known as the “Stark Law.” This law prohibits a physician (defined to include a doctor of medicine or osteopathy, a doctor of dental surgery or dental

medicine, a doctor of podiatric medicine, a doctor of optometry, or a chiropractor) from referring Medicare and Medicaid patients to certain types of entities with which the physician or any of the physician’s immediate family members have a

financial relationship, unless an exception to the law’s prohibition is met.

Subject to adherence to their respective criteria requirements, the self-referral prohibition contains a number of exceptions, including exceptions covering employment

or independent contractor arrangements, space and equipment leases, and recruitment agreements.

Sanctions within the Stark Law include significant civil penalties including over $25,000 for each violation, over $169,000 for schemes to circumvent

the Stark Law restrictions, and up to $10,000 for each day an entity fails to report required information and exclusion from the federal healthcare programs.

Violations of the Stark Law may also result in payment denials, false claim recoveries,

civil monetary penalties, and/or federal program exclusion.

Further, several states have enacted statutes similar in scope and purpose to the Stark Law.

These state laws may mirror the federal Stark Law or may be different in scope.

available guidance and enforcement activity associated with such state laws varies considerably.

The Physician Payments Sunshine Act, created under the ACA, and its implementing regulations require manufacturers of approved prescription 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 annually collect and report information on payments or transfers of value to physicians and teaching hospitals, as well

as investment interests held by physicians and their immediate family members.

The information reported each year is made publicly available on a searchable website.

Failure to submit required information may result in civil monetary penalties.

In addition, several states now require prescription drug companies to report expenses relating to the marketing and promotion of drug products and to report gifts and payments to individual

physicians in these states.

Other states prohibit various other marketing-related activities.

Still other states require the posting of information relating to clinical studies and their outcomes.

In addition, California, Connecticut, Nevada, and

Massachusetts require pharmaceutical companies to implement compliance programs and/or marketing codes.

Several additional states are considering similar proposals.

Compliance with these laws is difficult and time consuming, and companies that do

not comply with these state laws face civil penalties.

Prescription drug advertising is subject to federal, state and foreign regulations.

In the United States, the FDA regulates prescription drug promotion, including direct-to-consumer

Prescription drug promotional materials must be submitted to the FDA in conjunction with their first use.

Any distribution of prescription drug products and pharmaceutical samples must comply with the United States Prescription Drug

Marketing Act, or PDMA, a part of the FDCA.

In addition, Title II of the Federal Drug Quality and Security Act of 2013, known as the Drug Supply Chain Security Act, or DSCSA, has imposed new “track and trace” requirements on the distribution of

prescription drug products by manufacturers, distributors, and other entities in the drug supply chain.

The DSCSA requires product identifiers (i.e., serialization) on prescription drug products in order to eventually establish an electronic

interoperable prescription product system to identify and trace certain prescription drugs distributed in the United States and preempts existing state drug pedigree laws and regulations on this topic.

The DSCSA also establishes new requirements

for the licensing of wholesale distributors and third-party logistic providers.

The FDA is the process of finalizing regulations addressing wholesale distributors and third-party logistics providers.

We serialize our product at both the package

and homogeneous case level, pass serialization and required transaction information to our customers, and believe that we comply with all such requirements.

The Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, sets standards governing the

conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information that is stored or transmitted electronically.

These include standards for common healthcare transactions, such as:

information, plan eligibility, payment information and the use of electronic signatures;

unique identifiers for providers, employers, health plans and individuals;

and security, privacy, breach notification and enforcement.

HIPAA transaction

regulations establish form, format and data content requirements for most electronic healthcare transactions, such as healthcare claims that are submitted electronically.

The HIPAA privacy regulations establish comprehensive requirements relating

to the use and disclosure of protected health information.

The HIPAA security regulations establish minimum standards for the protection of protected health information that is stored or transmitted electronically.

The HIPAA breach notification

regulations establish the applicable requirements for notifying individuals, the HHS, and the media in the event of a data breach affecting protected health information.

Violations of the privacy, security and breach notification regulations are

punishable by civil and criminal penalties.

In addition to the federal HIPAA regulations, most states also have laws that regulate the collection, storage, use, retention, security, disclosure, transfer and other processing of health

information and other confidential, sensitive and personal data.

Certain of these laws grant individuals rights with respect to their information, and we may be required to expend significant resources to comply with these laws.

various states, such as California and Massachusetts, have implemented privacy laws and regulations, such as the California Confidentiality of Medical Information Act, that impose restrictive requirements regulating the use and disclosure of

personally identifiable information, including protected health information.

These laws in many cases are more restrictive than, and may not be preempted by, the HIPAA rules and may be subject to varying interpretations by courts and government

We have competitors both in the United States and internationally, including major multinational pharmaceutical companies, established biotechnology companies, specialty pharmaceutical

companies, universities and other research institutions.

Many of our competitors have significantly greater financial, manufacturing, marketing, product development, technical and human resources than we do.

Large pharmaceutical companies, in

particular, have extensive experience in clinical testing, obtaining marketing approvals, recruiting patients and manufacturing pharmaceutical products.

Some of these companies also have significantly greater research and marketing capabilities

than we do and may also have products that have been approved or are in late stages of development, and collaborative arrangements in our target markets with leading companies and research institutions.

Established pharmaceutical companies may

also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make the product candidates that we develop obsolete.

Mergers and acquisitions in the pharmaceutical and biotechnology

industries may result in even more resources being concentrated among a smaller number of our competitors.

As a result of all of these factors, our competitors may succeed in obtaining patent protection and/or marketing approval or discovering,

developing and commercializing products in our field before we do.

There are a large number of companies developing or marketing treatments for cancer, including many major pharmaceutical and biotechnology companies.

These treatments consist both of small

molecule drug products, such as traditional chemotherapy, as well as novel immunotherapies.

Our commercial opportunities could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have

fewer or less severe effects, are more convenient, have a broader label, are marketed more effectively, are reimbursed or are less expensive than any products that we may develop.

Our competitors also may obtain FDA, European Medicines Agency

(“EMA”) or other marketing approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

Even if the product

candidates we develop achieve marketing approval, they may be priced at a significant premium over competitive products if any have been approved by then, resulting in reduced competitiveness.

Human Capital Resources

We perform in a highly competitive industry and recognize that our continued success relies upon our ability to attract, develop and retain

a diverse team of talented individuals.

We place high value on the satisfaction and well-being of our employees and operate with fair labor standards and industry-competitive compensation and benefits.

As of April 12, 2022, we have ten full-time employees, which includes five research and development positions and five administrative

None of our employees are covered by collective bargaining agreements.

Compensation, Benefits and Development

Our approach to employee compensation and benefits is designed to deliver cash, equity and benefit programs that are competitive with those offered by leading companies in the biotechnology and

pharmaceutical industries to attract, motivate and retain talent with a focus on encouraging performance, promoting accountability and adherence to our values and alignment with the interests of our stockholders.

Our base pay program aims to compensate staff members relative to the value of the contributions of their role, which takes into account the skills, knowledge and abilities required to perform

each position, as well as the experience brought to the job.

We may also provide our employees with opportunities to earn cash and equity incentive compensation to reward the achievement of company-wide goals that are established annually and

designed to drive aspects of our strategic priorities that support and advance our strategy across our company.

Our employees are also eligible for the grant of equity awards under our long-term incentive program that are designed to align

interests of our employees with that of our stockholders.

All employees also participate in a regular performance measurement process through which staff receive performance and development feedback, which is taken into account in determining

annual compensation.

Our benefit programs are generally broad-based, promote health and overall well-being and emphasize saving for retirement.

All employees are eligible to participate in the same health and

retirement savings plans.

Code of Business Conduct and Ethics

We are committed to conducting business in accordance with the highest ethical standards.

Our Code of Conduct and Ethics emphasizes the importance of integrity, honesty, forthrightness, respect

and fairness.

Our Code of Conduct and Ethics applies to all our employees, including those who are integrated into the Company through acquisitions.

Health, Safety and Well-Being

We actively promote the safety, health and well-being of our employees.

We have continued to focus on employee safety throughout the COVID-19 pandemic by implementing extensive safety measures,

including without limitation, on-site COVID-19 testing protocols and flexible remote working options for most of our employees.

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