What changed in this filing

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Item 1. Business

2022-03-29 compared with 2021-02-16 · 1355 added, 1091 removed, 0 unchanged (100% of the section changed)

are a blank check company formed as a Delaware corporation for the purpose of effecting a merger, capital stock exchange, asset

acquisition, stock purchase, reorganization or similar business combination with one or more businesses, which we refer to as

our initial business combination.

While we may pursue an acquisition opportunity in any business industry or sector, we intend

to capitalize on our management team’s differentiated ability to source, acquire and manage a business in the healthcare

industry in the United States.

Our management team has an extensive track record of creating value for stockholders by acquiring

attractive businesses at disciplined valuations, investing in growth while fostering financial discipline and ultimately improving

financial results.

Management Team

management team is led by Rajiv Shukla, our Chairman and Chief Executive Officer, and Patrick A.

Sturgeon, our Chief

Financial Officer.

Shukla has been our Chairman and Chief Executive Officer since inception and has two decades of buyouts, investments and operations

experience in the healthcare industry.

Shukla served as Chairman and Chief Executive Officer of Constellation Alpha Capital

(“CNAC”), a Nasdaq-listed special purpose acquisition company, from June 2017 to August 2019.

CNAC raised $144 million in proceeds from a Nasdaq initial public offering and successfully closed its initial business combination

with DermTech, Inc., or DermTech, in August 2019.

DermTech is a molecular dermatology company that develops and markets non-invasive diagnostic

The transaction was financed in part with proceeds from a private placement transaction with investors including Farallon

Capital, Victory RS Science and Technology Fund, Irwin Jacobs, RTW and HLM Venture Partners.

August 2019, Mr.

Shukla has served as an independent director on the board of directors of Ocunexus Therapeutics, a

clinical stage biotech company.

From June 2013 to May 2015, Mr.

Shukla served as Chief Executive Officer of Pipavav

Defence & Offshore Engineering Company (now Reliance Naval and Engineering Ltd.), an Indian listed shipbuilding and defense

manufacturing company.

In this role, he successfully implemented an extensive financial restructuring project and sold control

to the Reliance ADA Group.

Between 2008 and 2013, Mr.

Shukla worked as an investor at ICICI Venture, Morgan Stanley

Investment Management and Citi Venture Capital International.

Throughout his investment career, Mr.

Shukla has been involved

with numerous investments in healthcare companies.

As a private equity investor, Mr.

Shukla was involved with numerous control

and minority healthcare investments and served as a member of the board of directors of I-ven Medicare, a hospital roll-up platform

comprising multiple control investments and significant minority stakes in tertiary care hospitals and outpatient treatment centers,

Ranbaxy Fine Chemicals Ltd, a roll-up of specialty chemicals and animal health businesses, Swiss Bio, a U.S.

based clinical

CRO, Bharat Biotech, a vaccine company, three specialty pharma companies:

Arch Pharmalabs, Malladi Drugs and Unimark Remedies.

From 2001 to 2006, Mr.

Shukla served as Senior Director at Pfizer, Inc.

In this role, he played a key role in

several acquisitions including Pharmacia in 2003, Meridica in 2004, Vicuron Pharmaceuticals and Idun Pharmaceuticals in 2005,

and Rinat Neuroscience in 2006.

Shukla also led the operational integration of these organizations into Pfizer across

multiple sites around the world.

Shukla graduated from Harvard University with a Masters in Healthcare Management and

Policy and received a Bachelors in Pharmaceutics from the Indian Institute of Technology.

Sturgeon has been our Chief Financial Officer since inception and has nearly two decades of experience with M&A and

equity capital market transactions in the healthcare and other sectors.

He has served as a Managing Director at Brookline Capital

Markets, a division of Arcadia Securities, LLC (“Brookline”) since March 2016.

At Brookline, Mr.

focuses on mergers and acquisitions, public financing, private capital raising, secondary offerings, and capital markets.

public financing front, he focuses on SPAC transactions, primarily underwritten initial public offerings and initial business

combinations.

From July 2013 to February 2016, Mr.

Sturgeon served as a Managing Director at Axiom Capital Management.

He worked at Freeman & Co.

from October 2002 to November 2011, where he focused on mergers and acquisitions

in the financial services sector.

Sturgeon received his B.S.

in Economics from the University of Massachusetts, Amherst

and his M.B.A in Finance from New York University.

performance of our management team does not guarantee either (i) success with respect to any business combination we

may consummate or (ii) that we will be able to identify a suitable candidate for our initial business combination.

The historical

performance record of our management team is not an indication of our future performance.

Additionally, in the course of their

respective careers, members of our management team have been involved in businesses and deals that were unsuccessful.

Rajiv Shukla, our Chief Executive Officer, and Patrick A.

Sturgeon, our Chief Financial Officer, none of our directors has experience

with blank check companies or special purpose acquisition companies.

In addition, our executive officers and directors may have

conflicts of interest with other entities to which they owe fiduciary or contractual obligations with respect to initial business

combination opportunities.

of our management team are not obligated to devote any specific number of hours to our matters but they intend to devote as much

of their time as they, in the exercise of their respective business judgement, deem necessary to our affairs until we have completed

our initial business combination.

The amount of time that any member of our management team will devote in any time period will

vary based on whether a target business has been selected for our initial business combination and the current stage of the business

combination process.

We do not have an employment agreement with any member of our management team.

believe our management team’s operating and transaction experience and relationships with companies will provide us with

a substantial number of potential business combination targets.

Over the course of their careers, the members of our management

team have developed a broad network of contacts and corporate relationships in the healthcare industry.

This network has grown

through the activities of our management team sourcing, acquiring and financing businesses, our management team’s relationships

with sellers, financing sources and target management teams and the experience of our management team in executing transactions

under varying economic and financial market conditions.

we may acquire a business in any industry, our focus will be on the healthcare industry in the United States.

the healthcare industry is attractive for a number of reasons:

Target Market.

The healthcare industry represents a significant target market, with total annual U.S.

health expenditure currently exceeding $3 trillion.

The Center for Medicare and Medicaid Services has estimated that total healthcare

spending was approximately 17.7% of total U.S.

Gross Domestic Product as of 2018, which CMS estimates will expand to $4.7 trillion

in 2023 (18.6% of estimated total U.S.

Gross Domestic Product) reflecting a CAGR of 5.2% from 2018.

The number of private companies

in the healthcare industry is significant, with a significant number of firms focused on various sub-sectors of the healthcare

value chain in the United States alone.

Additionally, the North American healthcare industry has been characterized by robust

M&A activity in recent years, averaging approximately $300 billion of annual M&A spend from 2015 to 2019 based on

Dealogic data.

Universe of Potential Targets.

We intend to focus our investment effort broadly across the healthcare

industry, which encompasses services, therapeutics, devices, diagnostics, healthcare technology and animal health.

concentrate on target companies in the healthcare industry with an enterprise value range between $500 million and $3 billion.

We estimate that there are approximately 480 healthcare companies that currently meet this criteria screened for companies that

either (i) have raised venture capital funding of above $100 million or (ii) are private equity portfolio companies

that had an estimated enterprise value of at least $100 million at the time of their acquisition (which occurred between

2010 and 2017), based on data from Pitchbook and Capital IQ.

We believe that our investment and operating expertise in healthcare

across multiple industry verticals will give us a large, addressable universe of potential targets.

The diversity of the target

universe and the number of largely uncorrelated sub-sectors maximizes the likelihood that the management team will be able

to identify and execute an attractive transaction.

Our management team believes that the complexity of the healthcare industry acts as a

barrier to entry, requiring investors to have significant sector-specific knowledge and expertise, such as an understanding

of the reimbursement environment and regulatory landscape, complex valuation methodologies, specialized accounting treatments,

and political considerations to identify and appropriately analyze investment opportunities.

Since 2016, U.S.

healthcare-focused special

purpose acquisition companies, or SPACs, have comprised approximately 3% of all completed U.S.

initial public offerings (excluding

closed-end funds and companies with market capitalizations of less than $50 million), based on data from Renaissance

Over the same time period, there have been seven completed and seven announced U.S.

healthcare-focused SPAC business

combinations as of September 11, 2020 which are currently pending, based on data from SPAC Research.

Total global healthcare expenditure has grown at a pace substantially above the rate of inflation

in recent years, and this growth is projected to continue over the years to come, driven by factors such as an aging population,

increased prevalence of chronic disease and improved access to healthcare.

While the size of healthcare spending has grown and

will continue to grow, this expense has put significant pressure on payors, including federal and state governments as well as

This dynamic has offered opportunities to services companies that can both control cost and improve the overall quality

of healthcare.

Additionally, the healthcare IPO market has experienced significant activity in the last five years, accounting

for approximately 40% of all U.S.

IPOs and consistently being ranked as the number one sector by IPO volume over the past five

Private funding by venture capital and private equity firms has also created a robust healthcare IPO pipeline with approximately

$117 billion of funding in U.S.

healthcare companies year to date in 2020, up from approximately $58 billion in 2016,

according to Pitchbook.

The healthcare sector represents approximately 46% of the total U.S.

IPO backlog based on the number of

proposed initial public offerings as of September 13, 2020 according to information from the NYSE IPO Backlog.

environment, characterized by clear investor demand, offers an opportune market to execute a healthcare IPO.

Differentiation

mission is to create attractive risk-adjusted returns for our stockholders.

We intend to capitalize on the ability of our

management team to identify, acquire and operate a business that will benefit from their involvement by utilizing the following

differentiating factors to our advantage:

Healthcare is a broad, diverse and truly local industry comprised of numerous sub-sectors that each require

unique institutional knowledge to be properly analyzed.

Our management team has the ability to draw on vast experience to drive

value creation for stockholders.

Our management team has an extensive network of relationships with Private Equity funds, industry executives, private owners,

advisors and other intermediaries that we believe will generate deal-sourcing opportunities.

The members of our management team have collectively executed or advised on some of the largest and most impactful healthcare

M&A transactions over the course of their careers.

We believe this experience will allow for compelling structuring solutions

that create true alignment between management and stockholders, as well as efficient negotiations and pricing.

Our management team and their affiliates have considerable experience with public market healthcare investments

We believe this experience will allow our team to effectively position the target company with public market investors.

Additionally, the ability to effectively access the capital markets to either fund growth or right-size a company’s

balance sheet provides management teams with additional flexibility while running a business.

● Operational

The members of our management team have decades of diverse experience operating businesses and driving value creation.

The team has successfully led businesses in various stages of their lifecycle including pre-revenue startups, growth businesses,

roll-ups and restructurings.

We believe this will allow for a diverse set of acquisition targets to be evaluated.

believe the collective experience of our management team and their affiliates will lead to many potential acquisition opportunities.

with our strategy, we have identified the following general criteria and guidelines that we believe are important in evaluating

prospective target businesses.

We will use these criteria and guidelines in evaluating acquisition opportunities, but we may decide

to enter into our initial business combination with a target business that does not meet these criteria and guidelines.

to filter our opportunities based on the following criteria:

● Opportunities

for organic growth and add-on acquisitions .

We will seek targets that we believe we can grow both organically and through

acquisitions.

We intend to leverage the industry experience and financial acumen of our management team to identify additional

operational improvement opportunities for the target business.

In addition, we believe that we can utilize our extensive networks

to source opportunities and execute additional transactions that will drive growth for our business combination target.

an unrecognized value proposition .

We will conduct due diligence with respect to potential business combination targets, with

a goal of identifying value that has been unrecognized and would allow us to invest in companies and buy assets at prices that

we believe to be below intrinsic value.

In the case of turnaround opportunities, we expect to only acquire companies where we

can utilize our operating experience, industry networks and capital to implement a turnaround plan that addresses key aspects

of underperformance.

The ideal turnaround candidates are those that may require a recapitalization, improvements in working capital

management, operational improvements that result in margin expansion, or those that could benefit from the application of new

technology that could improve productivity or result in new business orders.

of, or potential for, free cash flow generation .

We will seek one or more businesses or assets that have a history of, or

potential for, strong, stable free cash flow generation, with predictable and recurring revenue streams.

● Experienced

and motivated management team .

We will target one or more businesses or assets that have strong, experienced management teams

or those that provide a platform for us to assemble an effective and experienced management team.

We will focus on management

teams with a track record of driving revenue growth, enhancing profitability and creating value for their stockholders.

criteria are not intended to be exhaustive.

Any evaluation relating to the merits of a particular initial business combination

may be based, to the extent relevant, on these general guidelines as well as other considerations, factors and criteria that our

management team may deem relevant.

In the event that we decide to enter into our initial business combination with a target business

that does not meet the above criteria and guidelines, we will disclose that the target business does not meet the above criteria

in our stockholder communications related to our initial business combination, which would be in the form of proxy solicitation

materials or tender offer documents that we would file with the U.S.

Securities and Exchange Commission.

may need to obtain additional financing either to complete our initial business combination or because we become obligated to

redeem a significant number of our public shares upon completion of our initial business combination.

We intend to acquire a company

with an enterprise value significantly above the net proceeds of our initial public offering and concurrent private placement.

Depending on the size of the transaction or the number of public shares we become obligated to redeem, we may potentially utilize

several additional financing sources, including but not limited to the issuance of additional securities to the sellers of a target

business, debt issued by banks or other lenders or the owners of the target, a private placement to raise additional funds, or

a combination of the foregoing.

If we are unable to complete our initial business combination because we do not have sufficient

funds available to us, we will be forced to cease operations and liquidate the trust account.

In addition, following our initial

business combination, if cash on hand is insufficient to meet our obligations or our working capital needs, we may need to obtain

additional financing.

Business Combination

rules require that we must complete one or more business combinations having an aggregate fair market value of at least 80% of

the value of the assets held in the trust account (excluding the deferred underwriting commissions and taxes payable on the interest

earned on the trust account) at the time of our signing a definitive agreement in connection with our initial business combination.

Our board of directors will make the determination as to the fair market value of our initial business combination.

of directors is not able to independently determine the fair market value of our initial business combination, we will obtain

an opinion from an independent investment banking firm or another independent entity that commonly renders valuation opinions

with respect to the satisfaction of such criteria.

While we consider it unlikely that our board of directors will not be able

to make an independent determination of the fair market value of our initial business combination, it may be unable to do so if

it is less familiar or experienced with the business of a particular target or if there is a significant amount of uncertainty

as to the value of a target’s assets or prospects.

Additionally, pursuant to Nasdaq rules, any initial business combination

must be approved by a majority of our independent directors.

anticipate structuring our initial business combination either (i) in such a way so that the post-transaction company

in which our public stockholders own shares will own or acquire 100% of the equity interests or assets of the target business

or businesses, or (ii) in such a way so that the post-transaction company owns or acquires less than 100% of such interests

or assets of the target business in order to meet certain objectives of the target management team or stockholders, or for other

However, we will only complete an initial business combination if the post-transaction company owns or acquires

50% or more of the outstanding voting securities of the target or otherwise acquires a controlling interest in the target sufficient

for it not to be required to register as an investment company under the Investment Company Act.

Even if the post-transaction company

owns or acquires 50% or more of the voting securities of the target, our stockholders prior to the initial business combination

may collectively own a minority interest in the post-transaction company, depending on valuations ascribed to the target

and us in the initial business combination.

For example, we could pursue a transaction in which we issue a substantial number

of new shares in exchange for all of the outstanding capital stock of a target.

In this case, we would acquire a 100% controlling

interest in the target.

However, as a result of the issuance of a substantial number of new shares, our stockholders immediately

prior to our initial business combination could own less than a majority of our outstanding shares subsequent to our initial business

If less than 100% of the equity interests or assets of a target business or businesses are owned or acquired by the

post-transaction company, the portion of such business or businesses that is owned or acquired is what will be taken into

account for purposes of Nasdaq’s 80% fair market value test.

If the initial business combination involves more

than one target business, the 80% fair market value test will be based on the aggregate value of all of the transactions

and we will treat the target businesses together as the initial business combination for purposes of a tender offer or for seeking

stockholder approval, as applicable.

Business Combination Process

evaluating prospective business combinations, we expect to conduct a thorough due diligence review process that will encompass,

among other things, a review of historical and projected financial and operating data, meetings with management and their advisors

(if applicable), on-site inspection of facilities and assets, discussion with customers and suppliers, legal reviews and

other reviews as we deem appropriate.

We will also seek to utilize the expertise of our management team in analyzing software

and internet technology companies and evaluating operating projections, financial projections and determining the appropriate

return expectations given the risk profile of the target business.

are not prohibited from pursuing an initial business combination with a company that is affiliated with our sponsor, officers

or directors.

In the event we seek to complete our initial business combination with a company that is affiliated with our sponsor,

officers or directors, we, or a committee of independent directors, will obtain an opinion from an independent investment banking

firm or another independent entity that commonly renders valuation opinions that our initial business combination is fair to our

company from a financial point of view.

of our officers and directors presently have fiduciary or contractual obligations to other entities pursuant to which such officer

or director is or will be required to present a business combination opportunity.

Accordingly, if any of our officers or directors

becomes aware of a business combination opportunity which is suitable for an entity to which he or she has then-current fiduciary

or contractual obligations to present the opportunity to such entity, he or she will honor his or her fiduciary or contractual

obligations to present such opportunity to such entity.

We believe, however, that the fiduciary duties or contractual obligations

of our officers or directors will not materially affect our ability to complete our initial business combination.

and restated certificate of incorporation provides that we renounce our interest in any corporate opportunity offered to any director

or officer unless such opportunity is expressly offered to such person solely in his or her capacity as a director or officer

of our company and such opportunity is one we are legally and contractually permitted to undertake and would otherwise be reasonable

for us to pursue, and to the extent the director or officer is permitted to refer that opportunity to us without violating another

legal obligation.

officers and directors may become officers or directors of another special purpose acquisition company with a class of securities

intended to be registered under the Securities Exchange Act of 1934, as amended, or the Exchange Act, even prior to us entering

into a definitive agreement for our initial business combination.

as a Public Company

believe our structure will make us an attractive business combination partner to target businesses.

As a public company, we offer

a target business an alternative to the traditional initial public offering through a merger or other business combination with

Following an initial business combination, we believe the target business would have greater access to capital and additional

means of creating management incentives that are better aligned with stockholders’

interests than it would as a private

A target business can further benefit by augmenting its profile among potential new customers and vendors and aid in

attracting talented employees.

In a business combination transaction with us, the owners of the target business may, for example,

exchange their shares of stock in the target business for our shares of Class A common stock (or shares of a new holding

company) or for a combination of our shares of Class A common stock and cash, allowing us to tailor the consideration to

the specific needs of the sellers.

there are various costs and obligations associated with being a public company, we believe target businesses will find this method

a more expeditious and cost effective method to becoming a public company than the typical initial public offering.

initial public offering process takes a significantly longer period of time than the typical business combination transaction

process, and there are significant expenses in the initial public offering process, including underwriting discounts and commissions,

marketing and road show efforts that may not be present to the same extent in connection with an initial business combination

once a proposed initial business combination is completed, the target business will have effectively become public, whereas an

initial public offering is always subject to the underwriters’

ability to complete the offering, as well as general market

conditions, which could delay or prevent the offering from occurring or could have negative valuation consequences.

an initial business combination, we believe the target business would then have greater access to capital and an additional means

of providing management incentives consistent with stockholders’

interests and the ability to use its shares as currency

for acquisitions.

Being a public company can offer further benefits by augmenting a company’s profile among potential new

customers and vendors and aid in attracting talented employees.

we believe that our structure and our management team’s backgrounds will make us an attractive business partner, some potential

target businesses may view our status as a blank check company, such as our lack of an operating history and our ability to seek

stockholder approval of any proposed initial business combination, negatively.

are an “emerging growth company,”

as defined in Section 2(a) of the Securities Act, as modified by the JOBS Act.

As such, we are eligible to take advantage of certain exemptions from various reporting requirements that are applicable to other

public companies that are not “emerging growth companies”

including, but not limited to, not being required to comply

with the independent registered public accounting firm attestation requirements of Section 404 of the Sarbanes-Oxley Act,

reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements, and exemptions from

the requirements of holding a non-binding advisory vote on executive compensation and stockholder approval of any golden

parachute payments not previously approved.

If some investors find our securities less attractive as a result, there may be a

less active trading market for our securities and the prices of our securities may be more volatile.

addition, Section 107 of the JOBS Act also provides that an “emerging growth company”

can take advantage of the

extended transition period provided in Section 7(a)(2)(B) of the Securities Act for complying with new or revised accounting

In other words, an “emerging growth company”

can delay the adoption of certain accounting standards until

those standards would otherwise apply to private companies.

We intend to take advantage of the benefits of this extended transition

will remain an emerging growth company until the earlier of (1) the last day of the fiscal year (a) following the fifth

anniversary of the completion of our initial public offering, (b) in which we have total annual gross revenue of at least

$1.07 billion, or (c) in which we are deemed to be a large accelerated filer, which means the market value of our Class A

common stock that is held by non-affiliates exceeds $700 million as of the prior June 30 th , and (2) the

date on which we have issued more than $1.0 billion in non-convertible debt securities during the prior three-year period.

Additionally,

we are a “smaller reporting company”

as defined in Rule 10(f)(1) of Regulation S-K.

Smaller reporting companies

may take advantage of certain reduced disclosure obligations, including, among other things, providing only two years of audited

financial statements.

We will remain a smaller reporting company until the last day of the fiscal year in which (1) the market

value of our common stock held by non-affiliates equals or exceeds $250 million as of the end of the prior June 30 th ,

or (2) our annual revenues equaled or exceeded $100 million during such completed fiscal year and the market value of

our common stock held by non-affiliates exceeds $700 million as of the prior June 30 th .

funds available for an initial business combination initially in the amount of $96,500,000, after payment of $3,500,000 of deferred

underwriting fees, before fees and expenses associated with our initial business combination (other than deferred underwriting

fees), we offer a target business a variety of options such as creating a liquidity event for its owners, providing capital for

the potential growth and expansion of its operations or strengthening its balance sheet by reducing its debt or leverage ratio.

Because we are able to complete our initial business combination using our cash, debt or equity securities, or a combination of

the foregoing, we have the flexibility to use the most efficient combination that will allow us to tailor the consideration to

be paid to the target business to fit its needs and desires.

However, we have not taken any steps to secure third party financing

and there can be no assurance it will be available to us.

Our Initial Business Combination

are not presently engaged in, and we will not engage in, any operations for an indefinite period of time.

We intend to effectuate

our initial business combination using cash from the proceeds of our initial public offering and concurrent private placement,

the proceeds of the sale of our shares in connection with our initial business combination (pursuant to backstop agreements we

may enter into), shares issued to the owners of the target, debt issued to bank or other lenders or the owners of the target,

or a combination of the foregoing.

We may seek to complete our initial business combination with a company or business that may

be financially unstable or in its early stages of development or growth, which would subject us to the numerous risks inherent

in such companies and businesses.

our initial business combination is paid for using equity or debt securities, or not all of the funds released from the trust

account are used for payment of the consideration in connection with our initial business combination or used for redemptions

of our Class A common stock, we may apply the balance of the cash released to us from the trust account for general corporate

purposes, including for maintenance or expansion of operations of the post-transaction company, the payment of principal

or interest due on indebtedness incurred in completing our initial business combination, to fund the purchase of other companies

or for working capital.

may seek to raise additional funds through a private offering of debt or equity securities in connection with the completion of

our initial business combination, and we may effectuate our initial business combination using the proceeds of such offering rather

than using the amounts held in the trust account.

In addition, we intend to target businesses larger than we could acquire with

the net proceeds of our initial public offering and the concurrent private placement, and may as a result be required to seek

additional financing to complete such proposed initial business combination.

Subject to compliance with applicable securities

laws, we would expect to complete such financing only simultaneously with the completion of our initial business combination.

In the case of an initial business combination funded with assets other than the trust account assets, our proxy materials or

tender offer documents disclosing the initial business combination would disclose the terms of the financing and, only if required

by applicable law or stock exchange requirements, we would seek stockholder approval of such financing.

There are no prohibitions

on our ability to raise funds privately, or through loans in connection with our initial business combination.

our management will assess the risks inherent in a particular target business with which we may combine, we cannot assure our

stockholders that this assessment will result in our identifying all risks that a target business may encounter.

some of those risks may be outside of our control, meaning that we can do nothing to control or reduce the chances that those

risks will adversely impact a target business.

of Target Businesses

anticipate that target business candidates will be brought to our attention from various unaffiliated sources, including investment

bankers and investment professionals, as a result of being solicited by us by calls or mailings.

These sources may also introduce

us to target businesses in which they think we may be interested on an unsolicited basis, since many of these sources will know

what types of businesses we are targeting.

Our officers and directors, as well as our sponsor and their affiliates, may also bring

to our attention target business candidates that they become aware of through their business contacts as a result of formal or

informal inquiries or discussions they may have, as well as attending trade shows or conventions.

In addition, we expect to receive

a number of deal flow opportunities that would not otherwise necessarily be available to us as a result of the business relationships

of our officers and directors and our sponsor and their affiliates.

While we do not presently anticipate engaging the services

of professional firms or other individuals that specialize in business acquisitions on any formal basis, we may engage these firms

or other individuals in the future, in which event we may pay a finder’s fee, consulting fee, advisory fee or other compensation

to be determined in an arm’s length negotiation based on the terms of the transaction.

We will engage a finder only to the

extent our management determines that the use of a finder may bring opportunities to us that may not otherwise be available to

us or if finders approach us on an unsolicited basis with a potential transaction that our management determines is in our best

interest to pursue.

Payment of finder’s fees is customarily tied to completion of a transaction, in which case any such

fee will be paid out of the funds held in the trust account.

In no event, however, will our sponsor or any of our existing officers

or directors be paid any finder’s fee, reimbursement, consulting fee, monies in respect of any payment of a loan or other

compensation by the company prior to, or in connection with any services rendered for any services they render in order to effectuate,

the completion of our initial business combination (regardless of the type of transaction that it is).

None of our sponsor, executive

officers or directors, or any of their respective affiliates, will be allowed to receive any compensation, finder’s fees

or consulting fees from a prospective business combination target in connection with a contemplated initial business combination.

We have agreed to pay an affiliate of our sponsor a total of $10,000 per month for office space, utilities and secretarial and

administrative support and to reimburse our sponsor for any out-of-pocket expenses related to identifying, investigating

and completing an initial business combination.

Some of our officers and directors may enter into employment or consulting agreements

with the post-transaction company following our initial business combination.

The presence or absence of any such fees or

arrangements will not be used as a criterion in our selection process of an initial business combination candidate.

are not prohibited from pursuing an initial business combination with an initial business combination target that is affiliated

with our sponsor, officers or directors or making the initial business combination through a joint venture or other form of shared

ownership with our sponsor, officers or directors.

In the event we seek to complete our initial business combination with an initial

business combination target that is affiliated with our sponsor, officers or directors, we, or a committee of independent directors,

would obtain an opinion from an independent investment banking firm or another independent entity that commonly renders valuation

opinions that such an initial business combination is fair to our company from a financial point of view.

We are not required

to obtain such an opinion in any other context.

any of our officers or directors becomes aware of an initial business combination opportunity that falls within the line of business

of any entity to which he or she has pre-existing fiduciary or contractual obligations, he or she may be required to present

such business combination opportunity to such entity prior to presenting such business combination opportunity to us.

and directors currently have certain relevant fiduciary duties or contractual obligations that may take priority over their duties

of a Target Business and Structuring of our Initial Business Combination

rules require that we must complete one or more business combinations having an aggregate fair market value of at least 80% of

the value of the assets held in the trust account (excluding the deferred underwriting commissions and taxes payable on the interest

earned on the trust account) at the time of our signing a definitive agreement in connection with our initial business combination.

The fair market value of our initial business combination will be determined by our board of directors based upon one or more

standards generally accepted by the financial community, such as discounted cash flow valuation, a valuation based on trading

multiples of comparable public businesses or a valuation based on the financial metrics of M&A transactions of comparable

If our board of directors is not able to independently determine the fair market value of our initial business combination,

we will obtain an opinion from an independent investment banking firm or another independent entity that commonly renders valuation

opinions with respect to the satisfaction of such criteria.

While we consider it unlikely that our board of directors will not

be able to make an independent determination of the fair market value of our initial business combination, it may be unable to

do so if it is less familiar or experienced with the business of a particular target or if there is a significant amount of uncertainty

as to the value of a target’s assets or prospects.

We do not intend to purchase multiple businesses in unrelated industries

in conjunction with our initial business combination.

Subject to this requirement, our management will virtually have unrestricted

flexibility in identifying and selecting one or more prospective target businesses, although we will not be permitted to effectuate

our initial business combination with another blank check company or a similar company with nominal operations.

any case, we will only complete an initial business combination in which we own or acquire 50% or more of the outstanding voting

securities of the target or otherwise acquire a controlling interest in the target sufficient for it not to be required to register

as an investment company under the Investment Company Act.

If we own or acquire less than 100% of the equity interests or assets

of a target business or businesses, the portion of such business or businesses that are owned or acquired by the post-transaction company

is what will be taken into account for purposes of Nasdaq’s 80% fair market value test.

the extent we effect our initial business combination with a company or business that may be financially unstable or in its early

stages of development or growth we may be affected by numerous risks inherent in such company or business.

Although our management

will endeavor to evaluate the risks inherent in a particular target business, we cannot provide any assurances that we will properly

ascertain or assess all significant risk factors.

evaluating a prospective business target, we expect to conduct a thorough due diligence review, which may encompass, among other

things, meetings with incumbent management and employees, document reviews, interviews of customers and suppliers, inspection

of facilities, as well as a review of financial and other information that will be made available to us.

time required to select and evaluate a target business and to structure and complete our initial business combination, and the

costs associated with this process, are not currently ascertainable with any degree of certainty.

Any costs incurred with respect

to the identification and evaluation of a prospective target business with which our initial business combination is not ultimately

completed will result in our incurring losses and will reduce the funds we can use to complete another business combination.

of Business Diversification

an indefinite period of time after the completion of our initial business combination, the prospects for our success may depend

entirely on the future performance of a single business.

Unlike other entities that have the resources to complete business combinations

with multiple entities in one or several industries, it is probable that we will not have the resources to diversify our operations

and mitigate the risks of being in a single line of business.

In addition, we intend to focus our search for an initial business

combination in a single industry.

By completing our initial business combination with only a single entity, our lack of diversification

us to negative economic, competitive and regulatory developments, any or all of which may have a substantial adverse impact on

the particular industry in which we operate after our initial business combination, and

us to depend on the marketing and sale of a single product or limited number of products or services.

Ability to Evaluate the Target’s Management Team

we intend to closely scrutinize the management of a prospective target business when evaluating the desirability of effecting

our initial business combination with that business, our assessment of the target business’

management may not prove to

In addition, the future management may not have the necessary skills, qualifications or abilities to manage a public

Furthermore, the future role of members of our management team, if any, in the target business cannot presently be stated

with any certainty.

The determination as to whether any of the members of our management team will remain with the combined company

will be made at the time of our initial business combination.

While it is possible that one or more of our directors will remain

associated in some capacity with us following our initial business combination, it is unlikely that any of them will devote their

full efforts to our affairs subsequent to our initial business combination.

Moreover, we cannot provide any assurance that members

of our management team will have significant experience or knowledge relating to the operations of the particular target business.

cannot provide any assurance that any of our key personnel will remain in senior management or advisory positions with the combined

The determination as to whether any of our key personnel will remain with the combined company will be made at the time

of our initial business combination.

an initial business combination, we may seek to recruit additional managers to supplement the incumbent management of the target

We cannot provide any assurance that we will have the ability to recruit additional managers, or that additional managers

will have the requisite skills, knowledge or experience necessary to enhance the incumbent management.

May Not Have the Ability to Approve Our Initial Business Combination

may conduct redemptions without a stockholder vote pursuant to the tender offer rules of the SEC.

However, we will seek stockholder

approval if it is required by applicable law or applicable stock exchange listing requirements, or we may decide to seek stockholder

approval for business or other legal reasons.

Presented in the table below is a graphic explanation of the types of initial business

combinations we may consider and whether stockholder approval is currently required under Delaware law for each such transaction.

Type of Transaction

Purchase of assets

Purchase of stock of target not involving a merger with the company

Merger of target into a subsidiary of the company

Merger of the company with a target

Nasdaq’s listing rules, stockholder approval would be required for our initial business combination if, for example:

issue shares of Class A common stock that will be equal to or in excess of 20% of the number of shares of our Class A

common stock then outstanding (other than in a public offering);

of our directors, officers or substantial stockholders (as defined by Nasdaq rules) has a 5% or greater interest (or such persons

collectively have a 10% or greater interest), directly or indirectly, in the target business or assets to be acquired or otherwise

and the present or potential issuance of common stock could result in an increase in outstanding common stock or voting power

of 5% or more;

issuance or potential issuance of common stock will result in our undergoing a change of control.

Purchases of our Securities

we seek stockholder approval of our initial business combination and we do not conduct redemptions in connection with our initial

business combination pursuant to the tender offer rules, our sponsor, initial stockholders, directors, officers, advisors or their

affiliates may purchase public shares or public warrants in privately negotiated transactions or in the open market either prior

to or following the completion of our initial business combination.

There is no limit on the number of shares our initial stockholders,

directors, officers or their affiliates may purchase in such transactions, subject to compliance with applicable law and Nasdaq

However, they have no current commitments, plans or intentions to engage in such transactions and have not formulated any

terms or conditions for any such transactions.

If they engage in such transactions, they will not make any such purchases when

they are in possession of any material nonpublic information not disclosed to the seller or if such purchases are prohibited by

Regulation M under the Exchange Act.

We do not currently anticipate that such purchases, if any, would constitute a tender offer

subject to the tender offer rules under the Exchange Act or a going-private transaction subject to the going-private rules

under the Exchange Act;

however, if the purchasers determine at the time of any such purchases that the purchases are subject

to such rules, the purchasers will comply with such rules.

Any such purchases will be reported pursuant to Section 13 and

Section 16 of the Exchange Act to the extent such purchasers are subject to such reporting requirements.

None of the funds

held in the trust account will be used to purchase shares or public warrants in such transactions prior to completion of our initial

business combination.

purpose of any such purchases of shares could be to vote such shares in favor of the initial business combination and thereby

increase the likelihood of obtaining stockholder approval of the initial business combination or to satisfy a closing condition

in an agreement with a target that requires us to have a minimum net worth or a certain amount of cash at the closing of our initial

business combination, where it appears that such requirement would otherwise not be met.

The purpose of any such purchases of

public warrants could be to reduce the number of public warrants outstanding or to vote such warrants on any matters submitted

to the warrantholders for approval in connection with our initial business combination.

Any such purchases of our securities may

result in the completion of our initial business combination that may not otherwise have been possible.

In addition, if such purchases

are made, the public “float”

of our shares of Class A common stock or warrants may be reduced and the number

of beneficial holders of our securities may be reduced, which may make it difficult to maintain or obtain the quotation, listing

or trading of our securities on a national securities exchange.

sponsor, officers, directors and/or their affiliates anticipate that they may identify the stockholders with whom our sponsor,

officers, directors or their affiliates may pursue privately negotiated purchases by either the stockholders contacting us directly

or by our receipt of redemption requests submitted by stockholders following our mailing of proxy materials in connection with

our initial business combination.

To the extent that our sponsor, officers, directors or their affiliates enter into a private

purchase, they would identify and contact only potential selling stockholders who have expressed their election to redeem their

shares for a pro rata share of the trust account or vote against our initial business combination, whether or not such stockholder

has already submitted a proxy with respect to our initial business combination.

Our sponsor, officers, directors or their affiliates

will only purchase public shares if such purchases comply with Regulation M under the Exchange Act and the other federal securities

purchases by our sponsor, officers, directors and/or their affiliates who are affiliated purchasers under Rule 10b-18 under

the Exchange Act will only be made to the extent such purchases are able to be made in compliance with Rule 10b-18, which

is a safe harbor from liability for manipulation under Section 9(a)(2) and Rule 10b-5 of the Exchange Act.

Rule 10b-18 has

certain technical requirements that must be complied with in order for the safe harbor to be available to the purchaser.

officers, directors and/or their affiliates will not make purchases of common stock if the purchases would violate Section 9(a)(2)

or Rule 10b-5 of the Exchange Act.

We expect that any such purchases will be reported pursuant to Section 13 and

Section 16 of the Exchange Act to the extent such purchases are subject to such reporting requirements.

Rights for Public Stockholders upon Completion of our Initial Business Combination

will provide our public stockholders with the opportunity to redeem all or a portion of their shares of Class A common stock

upon the completion of our initial business combination at a per-share price, payable in cash, equal to the aggregate amount

then on deposit in the trust account as of two business days prior to the consummation of the initial business combination including

interest earned on the funds held in the trust account and not previously released to us to pay our taxes, divided by the number

of then outstanding public shares, subject to the limitations described herein.

The amount in the trust account is initially anticipated

to be approximately $10.00 per public share.

The per-share amount we will distribute to investors who properly redeem their

shares will not be reduced by the deferred underwriting commissions we will pay to the underwriters.

Our sponsor, officers and

directors have entered into a letter agreement with us, pursuant to which they have agreed to waive their redemption rights with

respect to any founder shares and placement shares and any public shares held by them in connection with the completion of our

initial business combination.

of Conducting Redemptions

will provide our public stockholders with the opportunity to redeem all or a portion of their public shares of Class A common

stock upon the completion of our initial business combination either (i) in connection with a stockholder meeting called

to approve the initial business combination or (ii) by means of a tender offer.

The decision as to whether we will seek stockholder

approval of a proposed initial business combination or conduct a tender offer will be made by us, solely in our discretion, and

will be based on a variety of factors such as the timing of the transaction and whether the terms of the transaction would require

us to seek stockholder approval under the law or stock exchange listing requirement.

Under Nasdaq rules, asset acquisitions and

stock purchases would not typically require stockholder approval while direct mergers with our company where we do not survive

and any transactions where we issue more than 20% of our outstanding common stock or seek to amend our amended and restated certificate

of incorporation would require stockholder approval.

If we structure an initial business combination with a target company in

a manner that requires stockholder approval, we will not have discretion as to whether to seek a stockholder vote to approve the

proposed initial business combination.

We may conduct redemptions without a stockholder vote pursuant to the tender offer rules

of the SEC unless stockholder approval is required by law or stock exchange listing requirements or we choose to seek stockholder

approval for business or other legal reasons.

So long as we obtain and maintain a listing for our securities on Nasdaq, we will

be required to comply with such rules.

stockholder approval of the transaction is required by law or stock exchange listing requirement, or we decide to obtain stockholder

approval for business or other legal reasons, we will, pursuant to our amended and restated certificate of incorporation:

the redemptions in conjunction with a proxy solicitation pursuant to Regulation 14A of the Exchange Act, which regulates the solicitation

of proxies, and not pursuant to the tender offer rules, and

proxy materials with the SEC.

the event that we seek stockholder approval of our initial business combination, we will distribute proxy materials and, in connection

therewith, provide our public stockholders with the redemption rights described above upon completion of the initial business

we seek stockholder approval, we will complete our initial business combination only if a majority of the outstanding shares of

common stock present and entitled to vote at the meeting to approve the initial business combination when a quorum is present

are voted in favor of the initial business combination.

A quorum for such meeting will consist of the holders present in person

or by proxy of shares of outstanding capital stock of the Company representing a majority of the voting power of all outstanding

shares of capital stock of the Company entitled to vote at such meeting.

Our initial stockholders will count toward this quorum

and pursuant to the letter agreement, our sponsor, officers and directors have agreed to vote any founder shares and placement

shares held by them and any public shares acquired during or after our initial public offering (including in open market and privately

negotiated transactions) in favor of our initial business combination.

For purposes of seeking approval of the majority of our

outstanding shares of common stock voted, non-votes will have no effect on the approval of our initial business combination

once a quorum is obtained.

As a result, in addition to our initial stockholders’

founder shares and placement shares, we

would need only 3,572,501, or 35.7%, of the 10,000,000 public shares sold in our initial public offering to be voted in favor

of an initial business combination (assuming all outstanding shares are voted and the placement shares issued to the underwriters

are voted in favor of the transaction) in order to have our initial business combination approved.

We intend to give approximately

30 days (but not less than 10 days nor more than 60 days) prior written notice of any such meeting, if required,

at which a vote shall be taken to approve our initial business combination.

These quorum and voting thresholds, and the voting

agreements of our initial stockholders, may make it more likely that we will consummate our initial business combination.

public stockholder may elect to redeem its public shares irrespective of whether they vote for or against the proposed transaction.

a stockholder vote is not required and we do not decide to hold a stockholder vote for business or other legal reasons, we will,

pursuant to our amended and restated certificate of incorporation:

the redemptions pursuant to Rule 13e-4 and Regulation 14E of the Exchange Act, which regulate issuer tender offers,

tender offer documents with the SEC prior to completing our initial business combination which contain substantially the same

financial and other information about the initial business combination and the redemption rights as is required under Regulation

14A of the Exchange Act, which regulates the solicitation of proxies.

the public announcement of our initial business combination, we or our sponsor will terminate any plan established in accordance

with Rule 10b5-1 to purchase shares of our Class A common stock in the open market if we elect to redeem our public

shares through a tender offer, to comply with Rule 14e-5 under the Exchange Act.

the event we conduct redemptions pursuant to the tender offer rules, our offer to redeem will remain open for at least 20 business

days, in accordance with Rule 14e-1(a) under the Exchange Act, and we will not be permitted to complete our initial business

combination until the expiration of the tender offer period.

In addition, we will not redeem any public shares unless our net

tangible assets will be at least $5,000,001 either immediately prior to or upon consummation of our initial business combination

and after payment of underwriters’

fees and commissions (so that we are not subject to the SEC’s “penny stock”

rules) or any greater net tangible asset or cash requirement which may be contained in the agreement relating to our initial business

If public stockholders tender more shares than we have offered to purchase, we will withdraw the tender offer and

not complete the initial business combination.

amended and restated certificate of incorporation provides that we may not redeem our public shares unless our net tangible assets

are at least $5,000,001 either immediately prior to or upon consummation of our initial business combination and after payment

of underwriters’

fees and commissions (so that we are not subject to the SEC’s “penny stock”

any greater net tangible asset or cash requirement which may be contained in the agreement relating to our initial business combination.

For example, the proposed initial business combination may require:

(i) cash consideration to be paid to the target or its

owners, (ii) cash to be transferred to the target for working capital or other general corporate purposes or (iii) the

retention of cash to satisfy other conditions in accordance with the terms of the proposed initial business combination.

event the aggregate cash consideration we would be required to pay for all shares of Class A common stock that are validly

submitted for redemption plus any amount required to satisfy cash conditions pursuant to the terms of the proposed initial business

combination exceed the aggregate amount of cash available to us, we will not complete the initial business combination or redeem

any shares, and all shares of Class A common stock submitted for redemption will be returned to the holders thereof.

on Redemption upon Completion of our Initial Business Combination if we Seek Stockholder Approval

Notwithstanding

the foregoing, if we seek stockholder approval of our initial business combination and we do not conduct redemptions in connection

with our initial business combination pursuant to the tender offer rules, our amended and restated certificate of incorporation

will provide that a public stockholder, together with any affiliate of such stockholder or any other person with whom such stockholder

is acting in concert or as a “group”

(as defined under Section 13 of the Exchange Act), will be restricted from

seeking redemption rights with respect to more than an aggregate of 15% of the shares sold in our initial public offering, which

we refer to as the “Excess Shares.”

Such restriction shall also be applicable to our affiliates.

We believe this restriction

will discourage stockholders from accumulating large blocks of shares, and subsequent attempts by such holders to use their ability

to exercise their redemption rights against a proposed initial business combination as a means to force us or our management to

purchase their shares at a significant premium to the then-current market price or on other undesirable terms.

our stockholders’

ability to redeem no more than 15% of the shares sold in our initial public offering without our prior

consent, we believe we will limit the ability of a small group of stockholders to unreasonably attempt to block our ability to

complete our initial business combination, particularly in connection with an initial business combination with a target that

requires as a closing condition that we have a minimum net worth or a certain amount of cash.

However, we would not be restricting

our stockholders’

ability to vote all of their shares (including Excess Shares) for or against our initial business combination.

Stock Certificates in Connection with Redemption Rights

may require our public stockholders seeking to exercise their redemption rights, whether they are record holders or hold their

shares in “street name,”

to either tender their certificates to our transfer agent up to two business days prior to

the vote on the proposal to approve the initial business combination, or to deliver their shares to the transfer agent electronically

using the Depository Trust Company’s DWAC (Deposit/Withdrawal At Custodian) System, at the holder’s option.

materials that we will furnish to holders of our public shares in connection with our initial business combination will indicate

whether we are requiring public stockholders to satisfy such delivery requirements.

Accordingly, a public stockholder would have

up to two days prior to the vote on the initial business combination to tender its shares if it wishes to seek to exercise its

redemption rights.

Given the relatively short exercise period, it is advisable for stockholders to use electronic delivery of

their public shares.

is a nominal cost associated with the above-referenced tendering process and the act of certificating the shares or delivering

them through the DWAC System.

The transfer agent will typically charge the tendering broker $80.00 and it would be up to the broker

whether or not to pass this cost on to the redeeming holder.

However, this fee would be incurred regardless of whether or not

we require holders seeking to exercise redemption rights to tender their shares.

The need to deliver shares is a requirement of

exercising redemption rights regardless of the timing of when such delivery must be effectuated.

foregoing is different from the procedures used by many special purpose acquisition companies.

In order to perfect redemption

rights in connection with their business combinations, many blank check companies would distribute proxy materials for the stockholders’

vote on an initial business combination, and a holder could simply vote against a proposed initial business combination and check

a box on the proxy card indicating such holder was seeking to exercise his or her redemption rights.

After the initial business

combination was approved, the company would contact such stockholder to arrange for him or her to deliver his or her certificate

to verify ownership.

As a result, the stockholder then had an “option window”

after the completion of the initial

business combination during which he or she could monitor the price of the company’s stock in the market.

If the price rose

above the redemption price, he or she could sell his or her shares in the open market before actually delivering his or her shares

to the company for cancellation.

As a result, the redemption rights, to which stockholders were aware they needed to commit before

the stockholder meeting, would become “option”

rights surviving past the completion of the initial business combination

until the redeeming holder delivered its certificate.

The requirement for physical or electronic delivery prior to the meeting

ensures that a redeeming holder’s election to redeem is irrevocable once the initial business combination is approved.

request to redeem such shares, once made, may be withdrawn at any time up to the date of the stockholder meeting.

if a holder of a public share delivered its certificate in connection with an election of redemption rights and subsequently decides

prior to the applicable date not to elect to exercise such rights, such holder may simply request that the transfer agent return

the certificate (physically or electronically).

It is anticipated that the funds to be distributed to holders of our public shares

electing to redeem their shares will be distributed promptly after the completion of our initial business combination.

our initial business combination is not approved or completed for any reason, then our public stockholders who elected to exercise

their redemption rights would not be entitled to redeem their shares for the applicable pro rata share of the trust account.

such case, we will promptly return any certificates delivered by public holders who elected to redeem their shares.

our initial proposed initial business combination is not completed, we may continue to try to complete an initial business combination

with a different target until 24 months from the closing of our initial public offering.

of Public Shares and Liquidation if no Initial Business Combination

amended and restated certificate of incorporation provides that we will have only 24 months from the closing of our initial

public offering to complete our initial business combination.

If we are unable to complete our initial business combination within

such 24-month period, we will:

(i) cease all operations except for the purpose of winding up, (ii) as promptly

as reasonably possible but not more than ten business days thereafter, redeem the public shares, at a per-share price, payable

in cash, equal to the aggregate amount then on deposit in the trust account including interest earned on the funds held in the

trust account and not previously released to us to pay our taxes (less up to $100,000 of interest to pay dissolution expenses),

divided by the number of then outstanding public shares, which redemption will completely extinguish public stockholders’

rights as stockholders (including the right to receive further liquidating distributions, if any), subject to applicable law,

and (iii) as promptly as reasonably possible following such redemption, subject to the approval of our remaining stockholders

and our board of directors, dissolve and liquidate, subject in the case of clauses (ii) and (iii) above to our obligations

under Delaware law to provide for claims of creditors and the requirements of other applicable law.

There will be no redemption

rights or liquidating distributions with respect to our warrants, which will expire worthless if we fail to complete our initial

business combination within the 24-month time period.

sponsor, officers and directors have entered into a letter agreement with us, pursuant to which they have waived their rights

to liquidating distributions from the trust account with respect to any founder shares and (along with the underwriters) placement

shares held by them if we fail to complete our initial business combination within 24 months from the closing of our initial

public offering.

However, if our sponsor, officers or directors acquired public shares in or after our initial public offering,

they will be entitled to liquidating distributions from the trust account with respect to such public shares if we fail to complete

our initial business combination within 24 months from the closing of our initial public offering.

sponsor, officers and directors have agreed, pursuant to a written agreement with us, that they will not propose any amendment

to our amended and restated certificate of incorporation (i) to modify the substance or timing of our obligation to allow

redemption in connection with our initial business combination or certain amendments to our charter prior thereto or to redeem

100% of our public shares if we do not complete our initial business combination within 24 months from the closing of our

initial public offering or (ii) with respect to any other provision relating to stockholders’

rights or pre-initial business

combination activity, unless we provide our public stockholders with the opportunity to redeem their shares of Class A common

stock upon approval of any such amendment at a per-share price, payable in cash, equal to the aggregate amount then on deposit

in the trust account including interest earned on the funds held in the trust account and not previously released to us to pay

our taxes divided by the number of then outstanding public shares.

However, we may not redeem our public shares unless our net

tangible assets are at least $5,000,001 either immediately prior to or upon consummation of our initial business combination and

after payment of underwriters’

fees and commissions (so that we are not subject to the SEC’s “penny stock”

If this optional redemption right is exercised with respect to an excessive number of public shares such that we cannot

satisfy the net tangible asset requirement (described above), we would not proceed with the amendment or the related redemption

of our public shares at such time.

expect that all costs and expenses associated with implementing our plan of dissolution, as well as payments to any creditors,

will be funded from amounts remaining out of the approximately $1,000,000 of proceeds held outside the trust account, although

we cannot provide any assurance that there will be sufficient funds for such purpose.

We will depend on sufficient interest

being earned on the proceeds held in the trust account to pay any tax obligations we may owe.

However, if those funds are not

sufficient to cover the costs and expenses associated with implementing our plan of dissolution, to the extent that there is any

interest accrued in the trust account not required to pay taxes, we may request the trustee to release to us an additional amount

of up to $100,000 of such accrued interest to pay those costs and expenses.

we were to expend all of the net proceeds of our initial public offering and the concurrent private placement, other than the

proceeds deposited in the trust account, and without taking into account interest, if any, earned on the trust account, the per-share redemption

amount received by stockholders upon our dissolution would be approximately $10.00.

The proceeds deposited in the trust account

could, however, become subject to the claims of our creditors which would have higher priority than the claims of our public stockholders.

We cannot provide any assurance that the actual per-share redemption amount received by stockholders will not be substantially

less than $10.00.

Under Section 281(b) of the DGCL, our plan of dissolution must provide for all claims against us to be

paid in full or make provision for payments to be made in full, as applicable, if there are sufficient assets.

These claims must

be paid or provided for before we make any distribution of our remaining assets to our stockholders.

While we intend to pay such

amounts, if any, we cannot provide any assurance that we will have funds sufficient to pay or provide for all creditors’

we will seek to have all vendors, service providers, prospective target businesses or other entities with which we do business

execute agreements with us waiving any right, title, interest or claim of any kind in or to any monies held in the trust account

for the benefit of our public stockholders, there is no guarantee that they will execute such agreements or even if they execute

such agreements that they would be prevented from bringing claims against the trust account including but not limited to fraudulent

inducement, breach of fiduciary responsibility or other similar claims, as well as claims challenging the enforceability of the

waiver, in each case in order to gain an advantage with respect to a claim against our assets, including the funds held in the

trust account.

If any third party refuses to execute an agreement waiving such claims to the monies held in the trust account,

our management will perform an analysis of the alternatives available to it and will only enter into an agreement with a third

party that has not executed a waiver if management believes that such third party’s engagement would be significantly more

beneficial to us than any alternative.

Examples of possible instances where we may engage a third party that refuses to execute

a waiver include the engagement of a third party consultant whose particular expertise or skills are believed by management to

be significantly superior to those of other consultants that would agree to execute a waiver or in cases where management is unable

to find a service provider willing to execute a waiver.

Marcum LLP, our independent registered public accounting firm, and the

underwriters of our initial public offering, have not executed agreements with us waiving such claims to the monies held in the

trust account.

addition, there is no guarantee that such entities will agree to waive any claims they may have in the future as a result of,

or arising out of, any negotiations, contracts or agreements with us and will not seek recourse against the trust account for

Our sponsor has agreed that it will be liable to us if and to the extent any claims by a third party for services

rendered or products sold to us, or a prospective target business with which we have entered into a written letter of intent,

confidentiality or similar agreement or business combination agreement, reduce the amount of funds in the trust account to below

the lesser of (i) $10.00 per public share and (ii) the actual amount per public share held in the trust account as of the

date of the liquidation of the trust account, if less than $10.00 per share due to reductions in the value of the trust assets,

less taxes payable, provided that such liability will not apply to any claims by a third party or prospective target business

who executed a waiver of any and all rights to the monies held in the trust account (whether or not such waiver is enforceable)

nor will it apply to any claims under our indemnity of the underwriters of our initial public offering against certain liabilities,

including liabilities under the Securities Act.

However, we have not asked our sponsor to reserve for such indemnification obligations,

nor have we independently verified whether our sponsor has sufficient funds to satisfy its indemnity obligations and believe that

our sponsor’s only assets are securities of our company.

Therefore, we cannot provide any assurance that our sponsor would

be able to satisfy those obligations.

None of our officers or directors will indemnify us for claims by third parties including,

without limitation, claims by vendors and prospective target businesses.

the event that the proceeds in the trust account are reduced below (i) $10.00 per public share or (ii) such lesser amount

per public share held in the trust account as of the date of the liquidation of the trust account, due to reductions in value

of the trust assets, in each case net of the amount of interest which may be withdrawn to pay taxes, and our sponsor asserts that

it is unable to satisfy its indemnification obligations or that it has no indemnification obligations related to a particular

claim, our independent directors would determine whether to take legal action against our sponsor to enforce its indemnification

While we currently expect that our independent directors would take legal action on our behalf against our sponsor

to enforce its indemnification obligations to us, it is possible that our independent directors in exercising their business judgment

may choose not to do so if, for example, the cost of such legal action is deemed by the independent directors to be too high relative

to the amount recoverable or if the independent directors determine that a favorable outcome is not likely.

We have not asked

our sponsor to reserve for such indemnification obligations and we cannot provide any assurance that our sponsor would be able

to satisfy those obligations.

Accordingly, we cannot provide any assurance that due to claims of creditors the actual value of

the per-share redemption price will not be less than $10.00 per public share.

will seek to reduce the possibility that our sponsor will have to indemnify the trust account due to claims of creditors by endeavoring

to have all vendors, service providers, prospective target businesses or other entities with which we do business execute agreements

with us waiving any right, title, interest or claim of any kind in or to monies held in the trust account.

Our sponsor will also

not be liable as to any claims under our indemnity of the underwriters of our initial public offering against certain liabilities,

including liabilities under the Securities Act.

We will have access to up to approximately $1,000,000 from the proceeds of our

initial public offering and the concurrent private placement with which to pay any such potential claims (including costs and

expenses incurred in connection with our liquidation, currently estimated to be no more than approximately $100,000).

that we liquidate and it is subsequently determined that the reserve for claims and liabilities is insufficient, stockholders

who received funds from our trust account could be liable for claims made by creditors.

In the event that our initial public offering

expenses exceed our estimate of $550,000, we may fund such excess with funds from the funds not to be held in the trust account.

In such case, the amount of funds we intend to be held outside the trust account would decrease by a corresponding amount.

the DGCL, stockholders may be held liable for claims by third parties against a corporation to the extent of distributions received

by them in a dissolution.

The pro rata portion of our trust account distributed to our public stockholders upon the redemption

of our public shares in the event we do not complete our initial business combination within 24 months from the closing of

our initial public offering may be considered a liquidating distribution under Delaware law.

If the corporation complies with

certain procedures set forth in Section 280 of the DGCL intended to ensure that it makes reasonable provision for all claims

against it, including a 60-day notice period during which any third-party claims can be brought against the corporation,

a 90-day period during which the corporation may reject any claims brought, and an additional 150-day waiting period

before any liquidating distributions are made to stockholders, any liability of stockholders with respect to a liquidating distribution

is limited to the lesser of such stockholder’s pro rata share of the claim or the amount distributed to the stockholder,

and any liability of the stockholder would be barred after the third anniversary of the dissolution.

if the pro rata portion of our trust account distributed to our public stockholders upon the redemption of our public shares in

the event we do not complete our initial business combination within 24 months from the closing of our initial public offering,

is not considered a liquidating distribution under Delaware law and such redemption distribution is deemed to be unlawful (potentially

due to the imposition of legal proceedings that a party may bring or due to other circumstances that are currently unknown), then

pursuant to Section 174 of the DGCL, the statute of limitations for claims of creditors could then be six years after the

unlawful redemption distribution, instead of three years, as in the case of a liquidating distribution.

If we are unable to complete

our initial business combination within 24 months from the closing of our initial public offering, we will:

all operations except for the purpose of winding up, (ii) as promptly as reasonably possible but not more than ten business

days thereafter, redeem the public shares, at a per-share price, payable in cash, equal to the aggregate amount then on deposit

in the trust account including interest earned on the funds held in the trust account and not previously released to us to pay

our taxes (less up to $100,000 of interest to pay dissolution expenses), divided by the number of then outstanding public shares,

which redemption will completely extinguish public stockholders’

rights as stockholders (including the right to receive

further liquidating distributions, if any), subject to applicable law, and (iii) as promptly as reasonably possible following

such redemption, subject to the approval of our remaining stockholders and our board of directors, dissolve and liquidate, subject

in the case of clauses (ii) and (iii) above to our obligations under Delaware law to provide for claims of creditors

and the requirements of other applicable law.

Accordingly, it is our intention to redeem our public shares as soon as reasonably

possible following our 24 th month and, therefore, we do not intend to comply with those procedures.

stockholders could potentially be liable for any claims to the extent of distributions received by them (but no more) and any

liability of our stockholders may extend well beyond the third anniversary of such date.

we will not be complying with Section 280, Section 281(b) of the DGCL requires us to adopt a plan, based on facts known

to us at such time that will provide for our payment of all existing and pending claims or claims that may be potentially brought

against us within the subsequent 10 years.

However, because we are a blank check company, rather than an operating company,

and our operations will be limited to searching for prospective target businesses to acquire, the only likely claims to arise

would be from our vendors (such as lawyers, investment bankers, etc.) or prospective target businesses.

As described above, pursuant

to the obligation contained in our underwriting agreement, we will seek to have all vendors, service providers, prospective target

businesses or other entities with which we do business execute agreements with us waiving any right, title, interest or claim

of any kind in or to any monies held in the trust account.

As a result of this obligation, the claims that could be made against

us are significantly limited and the likelihood that any claim that would result in any liability extending to the trust account

Further, our sponsor may be liable only to the extent necessary to ensure that the amounts in the trust account are

not reduced below (i) $10.00 per public share or (ii) such lesser amount per public share held in the trust account as of

the date of the liquidation of the trust account, due to reductions in value of the trust assets, in each case net of the amount

of interest withdrawn to pay taxes and will not be liable as to any claims under our indemnity of the underwriters of our initial

public offering against certain liabilities, including liabilities under the Securities Act.

In the event that an executed waiver

is deemed to be unenforceable against a third party, our sponsor will not be responsible to the extent of any liability for such

third-party claims.

we file a bankruptcy petition or an involuntary bankruptcy petition is filed against us that is not dismissed, the proceeds held

in the trust account could be subject to applicable bankruptcy law, and may be included in our bankruptcy estate and subject to

the claims of third parties with priority over the claims of our stockholders.

To the extent any bankruptcy claims deplete the

trust account, we cannot provide any assurance that we will be able to return $10.00 per share to our public stockholders.

Additionally,

if we file a bankruptcy petition or an involuntary bankruptcy petition is filed against us that is not dismissed, any distributions

received by stockholders could be viewed under applicable debtor/creditor and/or bankruptcy laws as either a “preferential

transfer”

or a “fraudulent conveyance.”

As a result, a bankruptcy court could seek to recover some or all amounts

received by our stockholders.

Furthermore, our board of directors may be viewed as having breached its fiduciary duty to our creditors

and/or may have acted in bad faith, thereby exposing itself and our company to claims of punitive damages, by paying public stockholders

from the trust account prior to addressing the claims of creditors.

We cannot provide any assurance that claims will not be brought

against us for these reasons.

public stockholders will be entitled to receive funds from the trust account only upon the earlier to occur of:

(i) the completion

of our initial business combination, (ii) the redemption of any public shares properly tendered in connection with a stockholder

vote to amend any provisions of our amended and restated certificate of incorporation (A) to modify the substance or timing

of our obligation to allow redemption in connection with our initial business combination or certain amendments to our charter

prior thereto or to redeem 100% of our public shares if we do not complete our initial business combination within 24 months

from the closing of our initial public offering or (B) with respect to any other provision relating to stockholders’

rights or pre-initial business combination activity, and (iii) the redemption of all of our public shares if we are

unable to complete our business combination within 24 months from the closing of our initial public offering, subject to

applicable law.

In no other circumstances will a stockholder have any right or interest of any kind to or in the trust account.

In the event we seek stockholder approval in connection with our initial business combination, a stockholder’s voting in

connection with the initial business combination alone will not result in a stockholder’s redeeming its shares to us for

an applicable pro rata share of the trust account.

Such stockholder must have also exercised its redemption rights as described

These provisions of our amended and restated certificate of incorporation, like all provisions of our amended and restated

certificate of incorporation, may be amended with a stockholder vote.

identifying, evaluating and selecting a target business for our initial business combination, we may encounter intense competition

from other entities having a business objective similar to ours, including other blank check companies, private equity groups

and leveraged buyout funds, and operating businesses seeking strategic business combinations.

Many of these entities are well

established and have extensive experience identifying and effecting business combinations directly or through affiliates.

many of these competitors possess greater financial, technical, human and other resources than we do.

Our ability to acquire larger

target businesses will be limited by our available financial resources.

This inherent limitation gives others an advantage in

pursuing the initial business combination of a target business.

Furthermore, our obligation to pay cash in connection with our

public stockholders who exercise their redemption rights may reduce the resources available to us for our initial business combination

and our outstanding warrants, and the future dilution they potentially represent, may not be viewed favorably by certain target

Either of these factors may place us at a competitive disadvantage in successfully negotiating an initial business

executive offices are located at 1177 Avenue of the Americas, 5 th Floor, New York, NY 10036 and our telephone

number is (646) 494-3296.

Our executive offices are provided to us by an affiliate of our sponsor.

We have agreed to pay an affiliate

of our sponsor a total of $10,000 per month for office space, utilities and secretarial and administrative support.

our current office space adequate for our current operations.

currently have two officers.

These individuals are not obligated to devote any specific number of hours to our matters but they

intend to devote as much of their time as they deem necessary, in the exercise of their respective business judgement, to our

affairs until we have completed our initial business combination.

The amount of time they will devote in any time period will

vary based on whether a target business has been selected for our initial business combination and the stage of the initial business

combination process we are in.

We do not intend to have any full time employees prior to the completion of our initial business

We do not have an employment agreement with any member of our management team.

Reporting and Financial Information

have registered our units, Class A common stock and warrants under the Exchange Act and have reporting obligations, including

the requirement that we file annual, quarterly and current reports with the SEC.

In accordance with the requirements of the Exchange

Act, our annual reports will contain financial statements audited and reported on by our independent registered public accountants.

will provide stockholders with audited financial statements of the prospective target business as part of the tender offer materials

or proxy solicitation materials sent to stockholders to assist them in assessing the target business.

In all likelihood, these

financial statements will need to be prepared in accordance with, or reconciled to, GAAP, or IFRS, depending on the circumstances,

and the historical financial statements may be required to be audited in accordance with the standards of the PCAOB.

These financial

statement requirements may limit the pool of potential targets we may conduct an initial business combination with because some

targets may be unable to provide such statements in time for us to disclose such statements in accordance with federal proxy rules

and complete our initial business combination within the prescribed time frame.

We cannot provide any assurance that any particular

target business identified by us as a potential business combination candidate will have financial statements prepared in accordance

with GAAP or that the potential target business will be able to prepare its financial statements in accordance with the requirements

outlined above.

To the extent that these requirements cannot be met, we may not be able to acquire the proposed target business.

While this may limit the pool of potential business combination candidates, we do not believe that this limitation will be material.

will be required to evaluate our internal control procedures for the fiscal year ending December 31, 2021 as required by

the Sarbanes-Oxley Act.

Only in the event we are deemed to be a large accelerated filer or an accelerated filer, and no longer

qualify as an emerging growth company, will we be required to have our internal control procedures audited.

A target company may

not be in compliance with the provisions of the Sarbanes-Oxley Act regarding adequacy of their internal controls.

The development

of the internal controls of any such entity to achieve compliance with the Sarbanes-Oxley Act may increase the time and costs

necessary to complete any such business combination.

We have filed a Registration Statement on Form 8-A with the SEC

to voluntarily register our securities under Section 12 of the Exchange Act.

As a result, we are subject to the rules and

regulations promulgated under the Exchange Act.

We have no current intention of filing a Form 15 to suspend our reporting

or other obligations under the Exchange Act prior or subsequent to the consummation of our initial business combination.

are an “emerging growth company,”

as defined in Section 2(a) of the Securities Act, as modified by the JOBS Act.

As such, we are eligible to take advantage of certain exemptions from various reporting requirements that are applicable to other

public companies that are not “emerging growth companies”

including, but not limited to, not being required to comply

with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act, reduced disclosure obligations regarding

executive compensation in our periodic reports and proxy statements, and exemptions from the requirements of holding a non-binding advisory

vote on executive compensation and stockholder approval of any golden parachute payments not previously approved.

If some investors

find our securities less attractive as a result, there may be a less active trading market for our securities and the prices of

our securities may be more volatile.

addition, Section 107 of the JOBS Act also provides that an “emerging growth company”

can take advantage of the

extended transition period provided in Section 7(a)(2)(B) of the Securities Act for complying with new or revised accounting

In other words, an “emerging growth company”

can delay the adoption of certain accounting standards until

those standards would otherwise apply to private companies.

We intend to take advantage of the benefits of this extended transition

will remain an emerging growth company until the earlier of (1) the last day of the fiscal year (a) following the fifth

anniversary of the completion of our initial public offering, (b) in which we have total annual gross revenue of at least

$1.07 billion, or (c) in which we are deemed to be a large accelerated filer, which means the market value of our shares

of Class A common stock that are held by non-affiliates exceeds $700 million as of the prior June 30 th ,

and (2) the date on which we have issued more than $1.0 billion in non-convertible debt during the prior three-year period.

References herein to “emerging growth company”

will have the meaning associated with it in the JOBS Act.

Additionally,

we are a “smaller reporting company”

as defined in Item 10(f)(1) of Regulation S-K.

Smaller reporting companies

may take advantage of certain reduced disclosure obligations, including, among other things, providing only two years of audited

financial statements.

We will remain a smaller reporting company until the last day of the fiscal year in which (1) the market

value of our common stock held by non-affiliates equals or exceeds $250 million as of the end of that year’s second

fiscal quarter, or (2) our annual revenues equaled or exceeded $100 million during such completed fiscal year and the

market value of our common stock held by non-affiliates exceeds $700 million as of the end of that year’s second

fiscal quarter.

is no material litigation, arbitration or governmental proceeding currently pending against us or any members of our management

team in their capacity as such.

Business Overview

Executive Summary

Humacyte, Inc.

is pioneering the development and manufacture of off-the-shelf, universally implantable, bioengineered human tissues with the goal of improving the lives of patients and transforming the practice of medicine.

We believe our technology has the potential to overcome limitations in existing standards of care and address the lack of significant innovation in products that support tissue repair, reconstruction and replacement.

We are leveraging our novel, scalable technology platform to develop proprietary, bioengineered, acellular human tissues for use in the treatment of diseases and conditions across a range of anatomic locations in multiple therapeutic areas.

We are initially using our proprietary, scientific technology platform to engineer and manufacture human acellular vessels, or HAVs.

Our investigational HAVs are designed to be easily implanted into any patient without inducing a foreign body response or leading to immune rejection.

We are developing a portfolio, or “cabinet”, of HAVs with varying diameters and lengths.

The HAV cabinet would initially target the vascular repair, reconstruction and replacement market, including vascular trauma;

arteriovenous (“AV”) access for hemodialysis;

peripheral arterial disease (“PAD”);

and coronary artery bypass grafting (“CABG”).

In addition, we are developing our HAVs for pediatric heart surgery and the delivery of cellular therapies, including pancreatic islet cell transplantation to treat Type 1 diabetes.

We will continue to explore the application of our technology across a broad range of markets and indications including the development of urinary conduit, trachea, esophagus and other novel cell delivery systems.

We believe there is substantial clinical demand for safe and effective vascular conduits to replace and repair blood vessels throughout the body.

Vascular injuries resulting from trauma are common in civilian and military populations, frequently resulting in the loss of either life or limb.

Existing treatment options in the vascular repair, reconstruction and replacement market include the use of autologous vessels and synthetic grafts, which we believe suffer from significant limitations.

For example, the use of autologous veins to repair traumatic vascular injuries can lead to significant morbidity associated with the surgical wounds created for vein harvest and prolonged times to restore blood flow to injured limbs, leading to an increased risk of amputation and infection.

Synthetic grafts are often contraindicated in the setting of vascular trauma due to higher infection risk that can lead to prolonged hospitalization and limb loss.

Given the competitive advantages our HAVs are designed to have over existing vascular substitutes, we believe that HAVs have the potential to become the standard of care and lead to improved patient outcomes and lower healthcare costs.

As of December 31, 2021, our HAVs have been implanted in approximately 471 patients.

We are currently conducting Phase II and Phase III trials of our 6 millimeter HAV across two therapeutic indications, vascular trauma and AV access for hemodialysis, as well as continuing long-term follow up of patients in our Phase II PAD studies.

We were granted Fast Track designation by the FDA for our 6 millimeter HAV for use in AV access for hemodialysis in 2014.

We also received the first Regenerative Medicine Advanced Therapy (“RMAT”) designation from the FDA, for the creation of vascular access for performing hemodialysis, in March 2017.

In addition, in 2018 our HAV product candidate was assigned a priority designation by the Secretary of Defense under Public Law 115-92, enacted to expedite the FDA’s review of products that are intended to diagnose, treat or prevent serious or life-threatening conditions facing American military personnel.

Upon completion of our Phase III trials, we intend to submit a Biologics License Application (“BLA”) to the FDA for an indication in vascular trauma in 2022 or 2023 and AV access for hemodialysis in 2023.

We have developed a novel paradigm for manufacturing human tissues that is intended to mimic key aspects of human physiology.

We have an 83,000 square foot bioprocessing facility housing our modular manufacturing process with the ability to manufacture HAVs of different diameters and lengths at commercial scale.

As we continue to expand production, we believe we will have the ability to take advantage of economies of scale to reduce costs of production.

We believe our established, controlled manufacturing process demonstrates a significant competitive advantage in the regenerative medicine market.

Our technology is protected by our patent portfolio, which includes certain patents licensed from parties as well as intellectual property generated internally at Humacyte.

Our patent portfolio is comprised of 15 families of patents, many of which generally relate to the scaffolds used to make our vessels, the composition of our vessels and systems and methods of manufacturing our vessels.

For more information, see “— Intellectual Property” below.

We intend to continue to shape our commercial and distribution strategy by indication and pursue collaborations with partners in markets where such partners provide strategic opportunities in launching our product candidates and enabling access to specific patient populations.

Our world-class senior management team and board of directors will be instrumental in helping us achieve our goals.

Our President and Chief Executive Officer, Laura Niklason M.D., PhD., who founded Legacy Humacyte (as defined below), is an internationally respected physician scientist and a world leader in regenerative medicine technologies.

Niklason is also a member of three national academies — Inventors, Medicine and Engineering.

Our current Chairman of the Board is Kathleen Sebelius, the former Secretary of the Department of Health and Human Services (“HHS”), and the former Governor of Kansas.

On August 26, 2021 (the “Closing Date”), Humacyte, Inc.

(“Legacy Humacyte”), a Delaware corporation, and Alpha Healthcare Acquisition Corp.

(“AHAC”), a Delaware corporation, consummated a merger pursuant to that certain Business Combination Agreement, dated as of February 17, 2021 (the “Merger Agreement”), by and among Legacy Humacyte, AHAC and Hunter Merger Sub (“Merger Sub”), a Delaware corporation and wholly owned subsidiary of AHAC.

As contemplated by the Merger Agreement, Merger Sub merged with and into Legacy Humacyte, with Legacy Humacyte continuing as the surviving corporation and as a wholly owned subsidiary of AHAC (the “Merger”).

On the Closing Date, AHAC changed its name to Humacyte, Inc.

and Legacy Humacyte changed its name to Humacyte Global, Inc.

Unless the context indicates otherwise, references in this Annual Report on Form 10-K to the “Company,” “Humacyte,” “we,” “us,” “our” and similar terms refer to Humacyte, Inc.

(formerly known as Alpha Healthcare Acquisition Corp.) and its consolidated subsidiaries (including Humacyte Global, Inc.) following the Merger.

References to “AHAC” refer to Alpha Healthcare Acquisition Corp.

prior to the Merger.

We have developed an approach that relies on two key complementary elements to address the significant market opportunity for the global treatment of patients in need of vascular replacement, repair and reconstruction, vascular access for dialysis and potential future indications including complex tissue and organ replacement and treatment of Type-1 diabetes:

• our proprietary scientific and engineering technology platform allows us to grow human tissues, which are ultimately decellularized and therefore expected to be non-immunogenic and universally implantable;

• our novel, scalable manufacturing paradigm is designed to allow us to produce thousands of HAVs per year at the time of commercial launch, with the ability to expand manufacturing to meet expected future global demand and the planned expansion of our pipeline of product candidates.

In the first employment of these platform and manufacturing approaches, we intend to develop a readily available “cabinet” of HAVs of varying diameters and lengths to address the significant unmet needs across multiple potential indications in vascular repair, reconstruction and replacement.

Illustration of our Proposed HAV “Cabinet” for Vascular Repair, Reconstruction, and Replacement

Our Proprietary Scientific Technology Platform

Our proprietary scientific technology platform uses primary human aortic vascular cells from a working cell stock, isolated from donor tissues and cryopreserved.

The working cell stock is expanded using traditional cell culture techniques, and the cells are transferred onto a biocompatible, biodegradable polymer mesh within a flexible, single-use bioreactor bag.

Over the course of weeks, the cells proliferate and build extracellular matrix while the polymer mesh degrades.

The resulting bioengineered vessel is comprised of the aortic vascular cells and their deposited extracellular matrix.

After completion of the culture period, we decellularize the bioengineered vessel using a proprietary combination of solutions.

The resulting HAV retains the extracellular matrix constituents and, therefore, the biomechanical properties of the bioengineered vessel, but is cleansed of the cells and cellular components that could induce a foreign body response or immune rejection following implantation.

Our functionally closed system allows for the HAV to be grown, decellularized and ultimately shipped within the same flexible bioreactor bag.

Our HAVs are designed to be shipped to hospitals, trauma centers and outpatient surgical settings, where they can then be stored at refrigerated temperatures for immediate use by removing each HAV from its packaging.

The following image summarizes key information about our proprietary scientific technology platform:

Our Novel Manufacturing Paradigm

We have developed a novel paradigm for manufacturing human tissues that is intended to mimic key aspects of human physiology.

Our proprietary manufacturing process was designed with a modular approach allowing us to produce HAVs in smaller batches for clinical trials and scale out to larger batches for commercial manufacturing.

The system used in our clinical trials from 2016 to 2021, including our Phase III trials, utilized a single tray within one growth drawer holding 10 HAVs per batch.

In 2021 we commenced supplying our ongoing clinical trials with HAVs produced in our current, commercial-scale LUNA200 system, which consists of 20 growth drawers per production unit for a total of 200 HAVs per batch.

Each growth drawer is capable of producing ten 42cm HAVs, each of which is contained within an individual bioreactor bag.

Inside a LUNA200, a tubing network connects all HAVs, allowing the entire system to share nutritive media.

In this way, a single LUNA200 can produce up to 200 HAVs (42cm in length) per batch while maintaining the critical operating parameters, such as biomechanical pulsing, that affect growth.

A thorough comparability assessment was performed to evaluate HAV batches produced in the single drawer system and used in Phase III studies versus the 20-drawer LUNA200 system.

The study assessed 22 separate comparisons on the identity, strength, quality, purity, and potency of the HAV product.

In this study, we observed that HAVs produced in the LUNA200 system were comparable to HAVs used in our Phase III trials.

Additionally, a crossover study, called V011, completed enrollment of 30 subjects to evaluate HAVs that are manufactured on Humacyte’s commercial LUNA200 platform with the primary goal to evaluate the safety, efficacy and immunogenicity of the LUNA200-manufactured HAVs.

Thus far in this trial we have observed comparable safety profile between HAV used in previous studies and the HAV manufactured in the LUNA200 commercial system.

The results of the comparability assessment and the 30-day results from the V011 crossover study were submitted to the FDA.

In 2021, the FDA authorized the use of HAVs produced in the commercial LUNA200 system to supply our ongoing clinical trials.

We plan to also use the LUNA200 system for anticipated commercial launches of the HAV if it is approved.

Our current 83,000 square foot manufacturing facility has space to further expand manufacturing capacity as needed to over 40 LUNA200 systems.

Currently, eight LUNA200 systems are installed and operational.

We believe that the LUNA200 can produce HAVs in diameter sizes from 3mm to 10mm and lengths from 10cm to 42cm, making the equipment suitable for the varied array of product candidates in our pipeline.

We intend to introduce a 13cm-long HAV line extension after commercial launch of the 42cm HAV for surgeries that require shorter segments of HAV in the setting of vascular trauma and repair.

Using our existing LUNA200 manufacturing equipment without modification, we believe we have the ability to generate 400 HAVs (13cm in length) or 200 HAVs (42cm in length) per manufactured batch.

We have designed our manufacturing system to be functionally closed, to utilize single-use disposable materials with aseptic connections, and to be fully automated, which allows us to control and maximize HAV production.

Based on observations to date, the HAV has withstood maximal pressures that are comparable to those reported for native arteries.

For example, the human aorta is reported to have rupture strengths around 1,400 mmHg, while human cerebral arteries rupture around 1,800 mmHg.

We have observed HAVs withstanding maximal pressures of approximately 3,200 mmHg before rupturing, making their mechanical properties on par with native human blood vessels.

Our Market Opportunity

We are a biotechnology company with Phase III clinical trials in two indications and a strong pipeline for additional products and indications.

Additionally, we have had significant interest from surgeons to use our HAV in life and limb saving surgeries as demonstrated by their requests to the FDA to use our HAV in multiple expanded access (compassionate use) cases where no alternative was available.

Our Initial Market Opportunity in Vascular Repair, Reconstruction and Replacement

We believe there is a significant market opportunity for our technology across a number of important clinical areas within vascular reconstruction and replacement including vascular trauma, AV access for hemodialysis, peripheral arterial disease, and adult cardiac surgery.

To treat these diseases and conditions, patients often require invasive cardiovascular surgery, which involves the use of alternative vascular synthetic materials or autologous vessels harvested from elsewhere in the body.

For more information about our evaluation of market opportunity, see “Risk Factors — Risks Related to the Development and Commercialization of Our Product Candidates — The sizes of the market opportunities for our product candidates have not been established with precision and are estimates that management believes to be reasonable.

If these market opportunities are smaller than we estimate or if any approval that we obtain is based on a narrower definition of the relevant patient population, our revenue and ability to achieve profitability might be materially and adversely affected.”

Vascular Trauma :

Arterial injuries resulting from vascular trauma are common in military and civilian populations, frequently resulting in the loss of life or limb.

In military populations, as the rate of battlefield fatalities has been declining due to faster evacuations and more robust protection from body armor, the rate of survivable vascular injuries has been increasing.

In civilian populations, trauma injuries are primarily caused by motor vehicle accidents, gun violence, mass casualty terrorist attacks, stabbings and blunt trauma.

We estimate that central or peripheral vascular injuries in civilian patients account for approximately 150,000 of all injuries reported in global trauma patients.

Furthermore, these injuries account for greater than 20% of all trauma-related deaths.

Civilian patients with central or peripheral vascular injuries are estimated to account for approximately 75,000 of all injuries reported in trauma patients in the United States, inclusive of urgent and iatrogenic vascular trauma injuries.

However, these injuries account for greater than 20% of all trauma-related deaths.

We believe our HAVs will be a promising alternative that can address critical gaps in existing treatment options for acute vascular injuries due to trauma.

We are developing our HAVs with the goal of providing an effective solution in all time-constrained surgical environments and in resource-limited, infection prone battlefield environments.

The ability to create immediately available, non-immunogenic, universally implantable material that is less susceptible to infection represents a clinically significant advantage over existing options.

Arteriovenous Access for Hemodialysis :

An estimated $5 to $6 billion per year is spent on hospital admissions in hemodialysis patients with infection and access complications.

In 2017, there were nearly 500,000 patients receiving hemodialysis in the United States.

Annually, at least 160,000 existing or new dialysis patients require a new AV access in the U.S.

and an additional 150,000 patients require a new AV access in Europe and Japan.

Hemodialysis patients are a chronically ill patient population, suffering an average of 1.8 hospital admissions, three visits to the emergency department, and four days hospitalized for infections each year.

The two most common causes of hospital admissions in hemodialysis patients are infection and access complications, resulting in an estimated total spend of $5 billion to $6 billion per year.

For hemodialysis patients, an infected access can lead to sepsis, which is life threatening, is the most expensive cause for hospitalization in the United States and carries at least a 10% overall mortality rate.

We believe that our HAVs, when used as AV access for hemodialysis, can decrease infections and dialysis access failures, which would improve patient outcomes and lower the burden of dialysis costs on the healthcare system.

We expect to file a BLA with the FDA, seeking approval for the use of HAV in AV access for hemodialysis, and to target our commercialization efforts particularly toward those patients who are at high risk of fistula failure or non-maturation, or for those patients at high risk of vascular access infection.

Peripheral Artery Disease (PAD) :

PAD is a cardiovascular disease of blood vessels located outside the brain and heart.

PAD occurs when plaque builds up in arteries that carry blood to the head, organs, and limbs.

PAD usually affects arteries in the legs, but it can also affect arteries that carry blood from heart to head, arms, kidneys, and stomach.

We believe our

HAVs can be used as a bypass conduit in patients with PAD.

Peripheral arterial bypass procedures are common with as many as 160,000 PAD related procedures reported annually in the U.S.

and over 550,000 annual PAD procedures estimated globally.

Expanding into markets outside the U.S., annual peripheral bypass procedures are nearly 170,000 per year in Europe, and approximately 220,000 per year in Asia.

While endovascular techniques have become available over the past ten years to treat an array of vascular occlusions, depending on the nature and length of the blockage these types of treatment options have met with both mixed success and durability compared to conventional surgical bypass.

Both angioplasty and stenting procedures provide near term success, however long-term durability has remained a question.

Type I Diabetes :

Type 1 diabetes, caused by auto-immune destruction of insulin-producing cells in the islets of the pancreas, is a devastating disease affecting more than 1.2 million people in the United States, and costing at least $10 billion to $14 billion annually.

In Europe, the number of patients suffering with Type 1 diabetes is estimated at approximately 2.2 million.

Even with the newer insulin delivery technologies, less than one-third of patients achieve consistent target blood sugar levels.

Pancreas transplantation is limited due to the associated morbidity and cost of the whole pancreas organ transplantation procedure.

As an alternative to pancreas transplantation, the “Edmonton Protocol” has been developed whereby insulin producing cells are transplanted into the portal vein in the liver.

However, the majority of the injected cells are lost to inflammation and clotting, and only 16% of Type 1 diabetes patients who receive the Protocol are cured long term.

We believe our HAVs present a means to deliver a therapeutic number of pancreatic islets to patients with Type 1 diabetes.

Pancreatic islets are embedded on the outer surface of our HAV and implanted as an AV graft, analogous to the outpatient procedure done for hemodialysis access.

After implantation, the islets have the potential to sense blood glucose and then respond by secreting appropriate levels of insulin to maintain glucose levels in the blood.

We have termed this new paradigm for pancreatic islet cell delivery the “Biovascular Pancreas.” Proof-of-concept studies in rodents and pigs have shown promise that the BVP can reduce glucose levels.

Studies in non-human primates are planned.

We believe that a reliable, low-risk, and easily implantable islet cell delivery method that could ensure the survival and functionality of a therapeutic number of islet cells in a human adult would be transformational for the treatment of Type 1 diabetes.

Coronary Artery Bypass Graft (“CABG”) :

CABG is a surgery used to treat a blockage or narrowing of one or more of the coronary arteries to restore the blood supply to the heart muscle.

We believe our HAVs can replace existing vascular substitutes and improve patient outcomes, particularly in obese patients or those suffering from diabetes, in whom the risks of saphenous vein harvesting are more substantial.

CABG procedures are common, with 350,000 CABG procedures reported annually in the U.S.

and over 765,000 annual CABG procedures globally.

Typically, a CABG operation involves the use of both the patient’s own artery and vein.

In patients who are obese, have diabetes, or who are very elderly, there are higher risks for vein harvest complications, including failure to heal the vein harvest incision, infection, and prolonged swelling of the operative leg.

Furthermore, complications from the vein harvest incision site are more common than complications from the chest incision in CABG patients.

It is estimated that approximately 20% of patients requiring bypass surgery have no suitable grafts available, with sources reporting as high as 45% of CABG patients are without suitable autologous vein.

Pediatric Heart Surgery :

We are developing a smaller diameter HAV product for use in pediatric heart surgery as a Blalock Taussig (“BT”) shunt.

The BT shunt is a surgical procedure that is used to increase pulmonary blood flow for the treatment of babies born with a complex congenital heart defect called Tetralogy of Fallot, a common type of “blue baby syndrome”.

In 2018, there were 4 million babies born in the United States and approximately 1,500 to 2,000 of these babies were born with Tetralogy of Fallot.

The BT shunt is a life-saving procedure for these babies, and we plan to submit an orphan drug application for use of our HAV as a BT shunt for infants born with cyanotic congenital heart defects.

Although 3 – 4mm inner diameter expanded polytetrafluoroethylene (“ePTFE”) grafts are currently used as the most common BT shunt, they suffer from limitations that impact morbidity and mortality in these infants.

Our Clinical and Pre-Clinical Stage Product Pipeline

The following table highlights key information about our current product pipeline:

We began clinical evaluations of our HAVs in December 2012, with the enrollment of the first Phase II patient in our V001 hemodialysis access trial in Europe.

Since then, we have completed one Phase II trial in the United States, and currently have seven trials either actively enrolling or in long-term follow-up.

HAVs have been implanted in approximately 79 clinical centers in six countries around the world, and by more than 100 practicing surgeons.

Overview of Clinical Trials Assessing the Safety and Efficacy of the HAV in Multiple Indications

Clinical Trial

Number Indication Begin

Enrollment Design/Phase Number of

Subjects Status Outcomes**

Vascular Trauma

V005 Vascular Trauma 2018 Phase II/III Single-arm Historical Comparator Unblinded Targeting 75± total 47 total (32 lower extremity) enrolled as of December 31, 2021 Enrolling Trial is currently enrolling

Dialysis Access

V001 Dialysis Access 2012 Phase II Single-arm 40 10-year follow-up ongoing 30-day PP:

Infection Rate/yr:

Number of Rejections:

V003 Dialysis Access 2013 Phase II Single-arm 20 Complete 2-year follow-up 30-day PP:

Infection Rate/yr:

Number of Rejections:

V006 Dialysis Access 2016 Phase III Prospective Randomized Blinded 355 total;

177 received HAV 178 received ePTFE 5-year follow-up ongoing 30-day PP HAV:

12-month SP HAV:

24-month SP HAV:

12-month SP ePTFE:

24-month SP ePTFE:

74% Infection Rate HAV/yr:

Infection Rate ePTFE/yr:

Number of HAV Rejections:

V007 Dialysis Access 2017 Phase III Prospective Randomized Blinded Target 240 total;

207 enrolled (as of December 31, 2021) Enrolling Trial is currently enrolling

V011 Dialysis Access 2019 Phase II (LUNA200 manufacturing system) 30 3-year follow-up ongoing 30-day PP:

Infection Rate HAV/yr:

Number of HAV Rejections:

Peripheral Arterial Disease

V002 Peripheral Arterial Disease 2013 Phase II Single-arm 20 10-year follow-up ongoing 30-day PP:

Infection Rate/yr:

Number of Rejections:

V004 Peripheral Arterial Disease 2016 Phase II Single-arm 15 5-year follow-up ongoing 30-day PP:

Infection Rate/yr:

Number of Rejections:

Number of Amputations:

___________________________

Primary Patency, which is the interval of time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis, or the time of measurement of patency, i.e.

patent without interventions.

Secondary Patency, which is the interval from the time of access placement until abandonment, i.e.

patent with or without interventions.

As of December 31, 2021, approximately 471 patients worldwide have received our HAVs for the treatment of trauma, AV access for hemodialysis, PAD, and in expanded access cases resulting in approximately 971 subject-years of exposure to the HAV.

Our cumulative HAV exposure is approximately 805 subject-years in the hemodialysis access population, 116 subject-years in the PAD population, and 50 subject-years in the arterial trauma population.

The longest our HAV has been in a patient and used for dialysis is more than eight years and there have been more than 100,000 estimated dialysis

sessions using our HAVs.

Additionally, a total of 17 expanded access/compassionate use cases have been granted by the FDA.

Throughout all of these trials, we have observed that our HAVs functioned as intended and provided functional blood flow to affected limbs.

We have also observed consistent durability with a strong tolerability profile.

Furthermore, we have observed no evidence of clinically relevant immunologic reactions to our HAVs, supporting the potential use of our HAVs as off-the-shelf, universally implantable, bioengineered human tissues.

Overall, the HAV has functioned well and as intended, across eight different clinical trials in three clinical indications.

The HAV has been implanted in approximately 471 patients, across approximately 79 clinical sites in six countries, over more than eight years (as of December 31, 2021).

Rates of primary and secondary patency were similar across trial designs and disease states, with 30-day primary patency ranging from 95% – 100%.

Six-month secondary patency ranges from 84% – 100%, and 12-month secondary patency ranges from 81% – 97%, across multiple clinical trials, disease states, and patient age ranges and demographics.

We have observed zero instances of clinical rejection of the HAV in any clinical trial over the past eight years, suggesting that the HAV was not immunologically rejected after implantation.

Based on clinical trial results to date, we have observed that the HAVs were highly resistant to infection, with an infection rate averaging approximately 1.3% per patient-year in our AV access trials, and low infection rates currently in our trauma and PAD trials.

Vascular graft infections are a potentially serious complication and can result in adverse outcomes such as sepsis, hospitalization, long-term antibiotic use, repeat procedures and even death.

HAVs Remodel with Host Cells After Implantation

Additionally, based on clinical samples obtained during our Phase II AV access trials and published in three peer reviewed journals, The Lancet in 2016, Science Translational Medicine in 2019, and in the Journal of Vascular Surgery in 2020, we observed that the HAV became populated with healthy, vascular cells from the patient.

As described in these publications, over time the patient’s cells have been observed to transform the HAV into a multi-layered living tissue similar to native blood vessels.

In these trials we have also observed ongoing cellular repair of HAV tissues that had been previously injured during cannulation with dialysis needles, which suggests that the recellularized HAV may be capable of self-healing.

The image below shows an HAV that had been implanted in a hemodialysis patient for 44 weeks, that had developed alpha-actin positive vascular smooth muscle cells throughout the wall (red staining in the left-hand panel), and had developed a layer of CD31+ endothelial cells on the inner luminal surface of the HAV (line of red endothelial cells indicated in the right-hand panel).

Histological Images of HAV Repopulated with the Patient’s Own Vascular Cells

Existing Options for Surgical Treatment of Vascular Disease Are Not Sufficient

The table below contains a summary of the efficacy of autologous veins, ePTFE grafts, cryopreserved human cadaveric veins, and preserved bovine veins.

For the treatment of vascular trauma, saphenous vein presents challenges in terms of time to procure the vein, and ePTFE grafts carry extremely high infection rates:

24% – 29% per patient year in the studies below.

Similarly, autogenous fistulas and ePTFE grafts for dialysis access have low functional patencies at six and 12 months, and ePTFE is burdened with high rates of annual infection:

3% – 17% in the studies below.

Both cryopreserved human cadaver vein, and preserved bovine veins, have low patency at 12 months, and also suffer from high rates of aneurysm formation.

Lastly, for bypass of PAD, vein has acceptable patency but is not available for all subjects, while ePTFE carries lower patencies and higher infection risk, and bovine vein becomes aneurysmal at unacceptably high rates.

Published Studies in Vascular Surgery

We derived the data in the table below from data contained in certain published papers on vascular trauma, hemodialysis and PAD between 2002 and the present.

These data are from different studies and thus are not directly comparable.

In addition, many of these papers reported on additional endpoints that are not included in the table below.

Indication Type of

Conduit Year Number of

Patients Published

Outcome Infection

(per patient-year) Rejection

Vascular Trauma Saphenous Vein (autologous) 2002 – 2012 24 12 months:

~78% function 4% N/A

2014 152 30 days:

~90% function N/A

ePTFE (synthetic graft) 2002 – 2012 25 12 months:

~50% function 24% N/A

2005 14 of 95 30 days:

~79% function 29%

Hemodialysis Access Fistula (autogenous) Post-2005 2,800 12 months:

2019 14892 6 months:

2017 6,439 N/A 4%

2018 602 6 months:

ePTFE (synthetic graft) 2013 128 6 months:

2019 > 400 N/A 3% – 17%

2020 > 3,000 12 months:

Cryovein (cryopreserved human cadaver vein) 2002 45 12 months:

2004 49 12 months:

~65% Aneurysm rate:

Procol (bovine vein) 2005 186 12 months:

66% Aneurysm rate:

3.2% 5.3% N/A

Peripheral Arterial Disease Saphenous Vein (autologous) 2008 60 12 months:

ePTFE (synthetic graft) 2008 61 12 months:

2013 101 12 months:

2011 273 12 months:

2013 496 N/A 3.8%

Procol (bovine vein) 2008 7 6 months:

50% 12 months:

50% Aneurysm Rate:

Proposed Indication #1:

Use of HAV to Repair Vascular Trauma

Overview of Vascular Trauma

Arterial injuries resulting from vascular trauma are common in military and civilian populations, frequently resulting in the loss of life or limb.

In civilian populations, trauma injuries are primarily caused by motor vehicle accidents, gun violence, mass casualty terrorist attacks, stabbings and blunt trauma.

Consequently, we believe there is an increasingly urgent unmet need for novel materials that are immediately available for permanent vascular repair for both civilian and military vascular trauma.

Options in Surgical Treatment of Vascular Trauma

Autologous vein is the preferred conduit for vascular repair.

However, harvesting of autologous vein is not always feasible, due to damage to vein or lower limb, prior vein harvest, inadequate size of the vein or venous disease.

Harvesting autologous vein is a serious operation that requires additional time and resources.

Delaying the time from injury to operative intervention from less than one hour, to three hours or greater, more than doubles the risk of limb amputation.

Limb amputation, in turn, almost triples the length of intensive care unit stay, nearly doubles the length of hospital stay, and is devastating to patient quality of life.

Additionally, the morbidity associated with saphenous vein harvest includes surgical site infections, chronic pain, and limb swelling.

Synthetic materials have been shown to be inferior to autologous vein in resistance to infection and durability and, therefore, are generally only used for vascular repair when autologous vein is not an option.

Our Solution for Vascular Trauma

We believe our HAVs will be a promising alternative that can address critical gaps in existing treatment options for acute vascular injuries due to trauma.

We are developing our HAVs with the goal of providing an effective solution in all time-constrained surgical environments and in resource-limited, infection prone battlefield environments.

Humacyte has a strong working relationship with the Department of Defense (“DoD”) that has led to a partnership over the last decade to support their unmet need to reconstruct and repair vascular injuries through the development of our HAVs.

As a result of this collaboration and partnership with the DoD, we anticipate Humacyte would supply HAVs for use in military hospitals to treat injured soldiers and veterans.

The DoD assigned a priority designation to the HAV technology under Public Law 115-92.

Under this law, FDA and DoD work together to expedite the development and review of critical technologies and therapies requested by DoD.

Additionally, we have received an approximately $7 million grant from the DoD for the continued development of our HAVs for vascular reconstruction and repair.

Our Current Phase II/III Trial for Vascular Trauma

Trial Design:

Our ongoing V005 trial is a single-arm, multi-center, non-randomized clinical trial to evaluate the efficacy, safety and tolerability of our 6 millimeter HAV in replacement or reconstruction of vascular tissues in patients with life or limb-threatening vascular trauma.

Since the V005 trial is a single-arm, non-randomized, open label study, we have the ability to track ongoing efficacy and safety.

The current primary efficacy endpoint evaluates primary patency of the HAV at 30 days.

Based on the results we have observed to date, and subject to discussions with the FDA regarding trial size, we expect that the final design of the trial will support the submission of a BLA in 2022 or 2023.

We anticipate that analysis of data from V005 will focus on patients with lower extremity injuries.

The final number of subjects to be enrolled and evaluated in the study is dependent on additional guidance from the FDA, but is currently estimated to approximate 75.

Status of Phase III Trial of HAV in Vascular Trauma (as of December 31, 2021)

Number Indication Begin

Enrollment Design/Phase Number of Subjects Status Outcomes**

___________________________

Primary Patency, which is the interval of time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis, or the time of measurement of patency, i.e.

patent without interventions.

Secondary Patency, which is the interval from the time of access placement until abandonment, i.e.

patent with or without interventions.

Current Trial Status:

During 2020, we increased the number of trial sites for the V005 trial in the United States, from seven to 20 sites.

We are currently working to further expand sites in the United States, as well as add additional sites in Poland and Israel.

Increasing the number of sites is expected to provide a broader patient cohort for enrollment in the trial, providing more extensive clinical exposure to differing types of vascular traumatic injury.

The range of trauma injuries in V005 has been broad, including penetrating trauma cases, blunt injury cases, and iatrogenic injuries.

Mechanisms of injury have included motor vehicle accidents, gunshot wounds, industrial accidents, falls, and iatrogenic injuries from other interventional or surgical procedures.

The HAVs have been placed throughout the body, including in the lower limbs, upper limb, and torso.

The HAV has been used to repair the axillary artery, femoral artery, popliteal artery and vein, and the brachial artery in the V005 trial.

Many of the injuries treated in the V005 trial, including industrial accidents, motor vehicle accidents, and some gunshot wounds, are contaminated injuries that are at elevated risk of graft infection.

Nonetheless, as of December 31, 2021, there has been only one report of HAV infection in any V005 subject, despite a number of instances where the HAV has been implanted into contaminated surgical fields of acute vascular wounds.

There have been several instances of local wound infections, but importantly only one of these instances has led to infection of the HAV material itself, which we believe represents a significant advantage of the HAV over ePTFE grafts, which have a higher propensity to become infected in contaminated or infected wound beds.

There have been no reports of limb amputation that occurred as a result of HAV malfunction or loss of patency.

The resistance to infection we have observed in trials to date is particularly important in traumatic injuries which are often caused by infected material (i.e., knife, car accident, blast injury).

In the figure below, a photograph is shown of an HAV that was used to repair both an artery and a vein in the knee of a patient who suffered a gunshot wound.

This patient was doing well at the 30-day follow-up visit with both repairs remaining patent and functional.

Intra-operative photograph of HAV repair of popliteal artery (left) and vein (right) in V005 subject.

Proposed Indication #2:

Use of the HAV for Arteriovenous Access for Hemodialysis

Overview of Hemodialysis and Existing Methods of Arteriovenous Access for Hemodialysis

End-stage renal disease (“ESRD”) develops when chronic kidney disease progresses to a point where either dialysis or a kidney transplant is required for the patient to survive.

For hemodialysis to be conducted, a point of vascular access to the patient’s circulatory system must be created, termed vascular access, so that blood can be transported from the body to the dialyzer and then back to the body.

The demand for vascular access conduits includes the need for both new hemodialysis patients who have progressed to ESRD requiring an initial access, and existing patients that require the replacement of their existing access.

There are currently three traditional methods for obtaining vascular access for hemodialysis:

an AV fistula, a synthetic graft, and a catheter.

Each of these vascular access methods has substantial limitations, as outlined below:

Three Traditional Methods for Obtaining Vascular Access for Hemodialysis

An AV fistula is created by surgically connecting a vein to an artery, typically in the patient’s arm.

Fistulae are often considered the preferred means of access for hemodialysis due to lower infection rates of approximately 0.5% – 1.5% per patient-year as well as long-term durability.

However, many patients are not suitable candidates for fistula placement, due to small vessel anatomy, advanced age, obesity or other comorbidities.

Approximately 40% of patients who undergo surgery for fistula creation will not gain any benefit from the surgery because the fistula lacks sufficient vein enlargement and increased blood flow, a process called fistula maturation, that is necessary for hemodialysis.

Additionally, during the period in which the fistula is maturing, catheters are generally used to provide the patient access for dialysis.

There is a high risk of infection and morbidity, and health care cost, associated with prolonged catheter dependence while waiting for the fistula to mature.

A catheter, which is tunneled underneath the skin and placed directly into a large vein in the patient, is generally the least desirable access solution.

Given the time necessary for fistulae to mature, the vast majority of patients in

the United States begin hemodialysis using a catheter while awaiting fistula maturation.

Catheters have rates of blood stream infections as high as 200% per patient-year, with high associated morbidity and health care costs.

Synthetic graft .

A synthetic graft, typically made from ePTFE and sewn between an artery and vein in the patient’s arm, is generally used in patients who are not candidates for fistulae.

The drawbacks of synthetic grafts include higher infection rates, which can be as high as 10% – 15% per patient-year, and gradual degradation of the non-healing ePTFE graft material caused by persistent needle punctures.

A recent systematic meta-analysis measuring the functional patency of ePTFE grafts shows that, on average, only 70% of ePTFE dialysis access grafts remain functional one year after implantation.

Distribution of Hemodialysis Access Modes in Use in the United States

Access Type Fistulae Catheters

Synthetic Grafts

Incident Patients:

At Initiation of Hemodialysis

16.7 % 80.3 % 3.0 %

Prevalent Patients:

For Ongoing Hemodialysis

64.5 % 18.9 % 16.6 %

Published Data in Hemodialysis Access

We derived the data in the table below from data contained in certain published papers on hemodialysis between 2002 and the present.

These data are from different studies and thus are not directly comparable.

In addition, many of these papers reported on additional endpoints that are not included in the table below.

Indication Type of

Conduit Year Number of

Patients Published Secondary

Patency Outcome Infection (per patient-year) Rejection Outcome

Fistula (autogenous) Post‑2005 2,800 12 months:

2019 14,892 6 months:

Hemodialysis Access 2017 6,439 N/A 4%

2018 602 6 months:

ePTFE (synthetic graft) 2013 128 6 months:

2019 > 400 N/A 3% – 17%

2020 > 3,000 12 months:

Cryovein (cryopreserved cadaver vein) 2002 45 12 months:

2004 49 12 months:

~65% Aneurysm rate:

Procol (bovine vein) 2005 186 12 months:

66% Aneurysm rate:

3.2% 5.3% N/A

Overview of HAV Experience in Hemodialysis Access:

A table listing our clinical trials of the HAV in hemodialysis access is included below.

We have implanted the HAV into approximately 372 total patients for hemodialysis access, for a total of more than 805 patient-years of exposure, as of December 31, 2021.

Throughout these trials, we have observed consistent and sustained high primary patency rates, ranging from 95% – 100% at 30 days.

Secondary patency of the HAV at 6 months ranges from 84% – 100%.

Consistently, we have observed zero instances of clinical rejection of any HAV in any hemodialysis access trial.

Implantation of HAV for Hemodialysis

We have also observed in multiple clinical trials that our HAVs had a low infection susceptibility during use for hemodialysis, with a rate lower than 1% per patient-year across all studies.

The low infection susceptibility we observed in our trials of our HAVs may be a result of the HAV’s potential to become a living tissue as it becomes populated by cells from the patient’s body.

Since living tissues are known to have resisted infection due to interactions with host white blood cells and immunological defense systems, it is possible that the repopulated HAV resists infection for the same reasons that native arteries and veins resist infections, as is observed with autogenous fistulas.

We have also observed early evidence of potential healing from the cells that repopulate the HAV after needle puncture for hemodialysis.

In examining HAV explanted segments we have observed healed needle cannulation tracts with cells expressing smooth muscle markers.

This self-healing indicates that the HAV may have repaired itself while being used as a hemodialysis access, which we believe is a distinct feature not present in synthetic materials, and, to our knowledge, has not been observed before for any other regenerative medicine product.

Our Current Phase II and Phase III Trials of the HAV in Hemodialysis Access

Clinical Trial

Number Indication Begin Enrollment Design/Phase Number of

Subjects Status Outcomes**

V001 Dialysis Access 2012 Phase II Single-arm 40 10‑year follow-up ongoing 30‑day PP:

Infection Rate/yr:

Number of Rejections:

V003 Dialysis Access 2013 Phase II Single-arm 20 Complete 2‑year follow-up 30‑day PP:

Infection Rate/yr:

Number of Rejections:

V006 Dialysis Access 2016 Phase III Prospective Randomized Blinded 355 total;

177 received HAV 178 received ePTFE 5‑year follow-up ongoing 30‑day PP HAV:

12‑month SP HAV:

24‑month SP HAV:

12‑month SP ePTFE:

24‑month SP ePTFE:

Infection Rate HAV/yr:

Infection Rate ePTFE/yr:

Number of HAV Rejections:

V007 Dialysis Access 2017 Phase III Prospective Randomized Blinded Target 240 total;

207 enrolled (as of December 31, 2021) Enrolling Trial is currently enrolling

V011 Dialysis Access 2019 Phase II (LUNA200 manufacturing system) 30 3‑year follow-up ongoing 30‑day PP:

Infection Rate HAV/yr:

Number of HAV Rejections:

___________________________

Primary Patency, which is the interval of time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis, or the time of measurement of patency, i.e.

patent without interventions.

Secondary Patency, which is the interval from the time of access placement until abandonment, i.e.

patent with or without interventions.

Long-Term Data from Early Phase II Trials in Hemodialysis:

V001 and V003

Phase II Trial Design and Current Outcomes:

We have completed or are in long-term follow-up on two open-label Phase II trials in 60 hemodialysis patients in the United States and Poland from December 2012 through May 2014, which we refer to as our V003 trial and V001 trial, respectively.

Both the V001 and V003 studies were designed as single-arm trials to assess the safety and efficacy of the HAV for hemodialysis access, with assessments of patency at 6, 12, 18 and 24 months.

In the 60 patients enrolled in these two studies, blood flow through all HAVs was appropriate for hemodialysis, averaging over 1,200 mL/minute.

Secondary patency for the two combined trials was 97% at six months, 89% at 12-months, and 81% at 18-months.

These results compare favorably to published reports of secondary patency for fistula of 51% – 61% at six months and 75% at 12 months.

Long-term results from the V001 trial showing five-year secondary patency of 58% were published in the European Journal of Vascular and Endovascular Surgery companion journal EJVES Vascular Forum in February 2022, and patients from the V001 trial are currently in a 10-year follow-up period.

Images and long-term results from Phase 2 V001 trial of HAV in AV Access

Phase III V006 AV Access Study

Trial Design:

Our V006 HUMANITY study is a prospective, multi-center, multinational, open-label, randomized, two-arm, comparative study.

Eligible study subjects were randomized to receive either a HAV or a commercially available ePTFE graft and followed to 24 months post-implantation by routine study visits.

After 24 months, subjects with a patent conduit are followed to five years post-implantation using a questionnaire at six-month intervals to ascertain patient and conduit status.

The primary endpoint for the V006 HUMANITY trial was a non-inferiority analysis of secondary patency compared to ePTFE, to be assessed when all subjects are at least 18 months post-implantation.

There were a total of 37 sites that participated in the study, enrolling a combined total of 355 subjects.

24-Month Results:

The V006 study enrolled 355 subjects who were roughly equally matched in terms of demographics and co-morbidities.

HAV subjects trended older (p=0.06) and had more prior strokes (p=0.02) than did ePTFE subjects.

Phase 3 V006 HUMANITY trial subject demographics

V006 Demographics

Age(years) 59.9 62.6 0.06

Male (%) 49.4% 49.7% NS

Caucasian (%) 65.2% 69.5% NS

Black (%) 27.5% 24.9% NS

Hispanic (%) 11.2% 14.7% NS

Asian / Other (%) 3.4% 2.3% NS

Body Mass Index (BMI) 29.2 28.9 NS

Hypertension (%) 79.8% 79.7% NS

Cardiac Disease (%) 50.6% 57.1% NS

Diabetes (%) 29.2% 32.8% NS

Prior Stroke (%) 5.6% 12.4% 0.02

The secondary patency of the HAV was greater than that of ePTFE at six and 12 months but lower at 18 and 24 months, an outcome that had not been modelled in the V006 trial design.

As per the pre-specified Cox Proportional Hazards test, the HAV did not achieve its primary efficacy endpoint regarding secondary patency.

In terms of safety, the HAV had a statistically significant lower rate of conduit infections compared to ePTFE.

Substantial differences in antibiotic use and need for hospitalization for infection were also noted in the V006 trial, all favoring the HAV.

The safety advantage of the HAV over ePTFE may be clinically important as infection and sepsis are the second most common cause of death in dialysis patients.

Phase 3 V006 HUMANITY trial secondary patency results

Secondary Patency 6 months 12 months 18 months 24 months

HAV HUMANITY [Mean (95% CI)]

92%(87 – 95%) 82% (75 – 87%) 73% (65 – 79%) 67% (59 – 74%)

ePTFE HUMANITY [Mean (95% CI)] 87% (81 – 85%) 80% (73 – 85%) 77% (70 – 83%) 74% (67 – 81%)

Cox Proportional Hazards Model for Time to Loss of Secondary Patency

Treatment Group

(HAV vs ePTFE) Hazard Ratio Non-inferiority

Margin Hazard Non-inferiority

Demonstrated (Yes/No)

Estimate 95% CI

12 months 0.869 (0.528, 1.431) 1.491 Yes

24 months 1.284 (0.867, 1.903) 1.488 No

Phase 3 V006 HUMANITY trial rates of infection

The reported SAEs related to the HAV and ePTFE in the V006 trial, in this patient population, which typically has a high prevalence of existing medical conditions, are detailed in the table below.

SAEs Reported in V006 Phase III Clinical Study in AV Access

Description of SAE Number of SAEs

(% of total subjects)

Number of subjects in V006 study 177 178

General disorders and administration conditions:

Implant site extravasation 0(0.0)% 1(0.6)%

Infections and infestations:

Vascular access site infection 0(0.0)% 5(2.8)%

Injury, poisoning and procedural complications:

Anastomotic stenosis 1(0.6)% (0.0)%

Vascular access site hematomas 1(0.6)% (0.0)%

Vascular access site hemorrhage 0(0.0)% 3(1.7)%

Vascular access site pain 1(0.6)% 0(0.0)%

Vascular access site pseudoaneurysm 10(5.6)% 0(0.0)%

Vascular access site rupture 2(1.1)% 0(0.0)%

Vascular access site thrombosis 41(23.2)% 28(15.7)%

Skin and subcutaneous tissue disorders:

Skin necrosis 0(0.0)% 1(0.6)%

Vascular disorders:

Steal syndrome 2(1.1)% 2(1.1)%

Subclavian vein occlusion 0(0.0)% 1(0.6)%

Vascular stenosis 34(19.2)% 27(15.2)%

Venous stenosis 3(1.7)% 9(0.0)%

Through an Analysis of Panel Reactive Antibodies (“PRA”) in the V006 trial, we observed that subjects that received the ePTFE grafts were more likely to develop antibodies against human tissues, and to become more difficult to crossmatch for a future kidney transplant, than were patients who received the HAV.

While the cause of this improvement in patient responses with the HAV is not clear, this may have been related to the lower number of severe infection events in HAV patients as compared to ePTFE patients in V006.

The percentage of women becoming sensitized (i.e.

cPRA values > 20%) was notably higher in the ePTFE group than the HAV group.

Phase 3 V006 HUMANITY trial % of patients developing antibodies against human tissues

We also observed differences in the remodeling of the HAV and ePTFE implants in the V006 trial.

Consistent with earlier observations from Phase II studies, microscopic examination of samples from HAV and ePTFE subjects suggest that the HAVs may have repopulated with host cells and microvasculature, while ePTFE grafts did not repopulate with cells and, in certain cases, fractured at sites of needle cannulation for hemodialysis (“G” is graft;

“D” is defect’ “T” is thrombus (clot);

“L” is lumen;

and “A” is adventitia):

Phase 3 V006 HUMANITY trial microscopic examination of samples from ePTFE and HAV subjects

Comparison of flow rates within the HAV and ePTFE conduits revealed similarities in blood flow and diameter over the 24-month period of the trial.

Bar graphs below display average blood flow rate, maximal blood flow rate, and mid-graft diameters, all of which were measured by periodic ultrasound examinations.

Diameters of the HAV remained close to the nominal 6.0 millimeter diameter.

Average blood flow rates exceeded 1.0 liters/minute, which is generally considered suitable for efficient hemodialysis.

Phase 3 V006 HUMANITY trial blood-flow rates and vessel diameters

Overall, although the primary efficacy endpoint concerning secondary patency was not met, the HAV performed in the V006 trial as was expected, based upon HAV performance in previous Phase II trials in hemodialysis and in other clinical applications.

This outcome was due at least in part to unexpectedly high patency of the ePTFE grafts, particularly after 12 months.

While the cause of this unexpectedly high patency is not clear, it is possible that study-mandated ultrasounds and examinations may have led to more aggressive vigilance with ePTFE grafts to maintain patency.

In addition, the age and comorbidities of HAV subjects in V006 was somewhat worse than for ePTFE subjects.

In the V006 trial, the HAV displayed significantly fewer infections than did the ePTFE grafts.

This was associated with fewer instances of immune sensitization in HAV subjects as compared to ePTFE subjects, which could translate to easier kidney transplantation at future times.

Similar to prior studies, we observed that the HAV had good durability, blood flow rates and diameters similar to ePTFE grafts, and also host cell remodelling that was superior to that of ePTFE grafts.

Phase III V007 AV Access Study

Trial Design:

We are currently enrolling a Phase III trial, called V007, in 240 patients with ESRD.

V007 is a Phase III, prospective, multi-center, open label, randomized, two-arm comparative study conducted in the United States.

The V007 trial is designed to assess the usability of the HAV for dialysis at six and 12 months as a comparison to autogenous fistulas, which are known to exhibit a high rate of early maturation failure of approximately 40% at six months.

Patients in the study are randomized to receive either the HAV for vascular access or an autogenous AV fistula.

The objective of V007 is to compare the safety and efficacy of our 6 millimeter HAV to autogenous AV fistula for functional hemodialysis access.

Eligible study subjects in V007 are randomized to receive either an HAV or an autogenous fistula and followed to 24 months post-implantation by routine study visits.

After 24 months, patients with functional accesses will be followed for up to five years.

Efficacy endpoints include useability for dialysis at six and 12 months, as well as a comparison of secondary patency via a time-to-event analysis of all subjects at 12 months.

Additional safety endpoints include the rate of dialysis access-related infections for HAV and fistula subjects.

Current Trial Status:

As of December 31, 2021, there were 207 patients enrolled in the V007 trial, out of a target enrollment of 240 total.

We currently expect to complete the V007 trial in time to support a BLA filing for the use of HAV in AV access for hemodialysis in 2023.

Proposed Indication #3:

Peripheral Arterial Disease

PAD involves partial or complete occlusion of blood vessels in the peripheral circulation and is a major cause of morbidity and mortality in the developed world.

Patients with severe PAD undergo peripheral arterial bypass surgery where a conduit is implanted above and below the area of the arterial obstruction, to provide a “bypass” route for blood to flow around the blocked artery.

The vast majority of these operations are performed in the lower limb.

Other surgical alternatives include minimally invasive approaches such as stenting and angioplasties that are suitable for smaller atherosclerotic lesions and can delay — but oftentimes not prevent — the ultimate need for surgical revascularization.

Published Data in PAD

We derived the data in the table below from data contained in certain published papers on PAD between 2008 and the present.

These data are from different studies and thus are not directly comparable.

In addition, many of these papers reported on additional endpoints that are not included in the table below.

Indication Type of

Conduit Year Number of

Patients Published Secondary Patency Outcome Infection (per patient-year) Rejection Outcome

Peripheral Arterial Disease Saphenous Vein (autologous) 2008 60 12 months:

– 86% N/A N/A

ePTFE 2008 61 12 months:

(synthetic graft) 2013 101 12 months:

76% – 89% N/A N/A

2011 273 12 months:

2013 496 N/A 3.8%

Procol 2008 7 12 months:

(bovine vein) Aneurysm Rate:

We have observed strong patency rates and no reported cases of infection for the HAV in PAD in clinical studies to date.

We are developing our 6 millimeter HAV for use as a bypass conduit for patients with PAD.

We are conducting two Phase II trials to evaluate the safety and efficacy of our 6 millimeter HAV for use as a bypass conduit with PAD, which we refer to as our V002 and V004 trials.

For both of these Phase II trials, the HAV is being implanted as a femoral popliteal bypass graft in patients with PAD.

Our Current Phase II Trials of the HAV in PAD

Number Indication Begin

Enrollment Design/

Phase Number of

Subjects Status Outcomes**

V002 Peripheral 2013 Phase II 20 10-year 30-day PP:

Arterial Disease Single-arm follow-up 6-month SP:

ongoing 12-month SP:

Infection Rate/yr:

Number of Rejections:

V004 Peripheral 2016 Phase II 15 5-year 30-day PP:

Arterial Disease Single-arm follow-up 6-month SP:

ongoing 12-month SP:

Infection Rate/yr:

Number of Rejections:

Number of Amputations:

___________________________

Primary Patency, which is the interval of time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis, or the time of measurement of patency, i.e.

patent without interventions.

Secondary Patency, which is the interval from the time of access placement until abandonment, i.e.

patent with or without interventions.

Trial Design:

Both our V004 and V002 trials are prospective, open-label, single treatment arm, multi-center studies.

We enrolled 20 patients in our V002 trial in Poland, and 15 patients in our V004 trial in the United States.

Both trials have the primary objectives of evaluating the safety of the HAV as a femoral-to-popliteal bypass graft, and determining the primary, primary assisted, and secondary patency over 12 and 24 months.

Current Trial Status and Outcomes:

V002 enrolled a total of 20 patients between the ages of 54 and 79 at three clinical sites.

24-month results of the V002 trial were published in 2020.

After censoring for three deaths (none of which were determined to be related to the HAV or the implant procedure), we observed 24-month primary, primary assisted and secondary patency rates of 58%, 58%, and 74%, respectively.

We observed through ultrasound data that the HAVs were mechanically stable during the follow-up period and did not develop aneurysmal dilatation in any patient.

Overall, we also determined through the histological assessment of explanted specimens that there were normal vascular cells within the HAV and there was no infection or signs of immunological reaction to the graft.

There have been no HAV-related infections reported during the V002 trial as of December 31, 2021, and no amputations of the treated extremity.

A sub-set of seven V002 subjects consented for long-term follow-up computerized tomography (“CT”) angiograms, which were obtained at 48 to 52 months after HAV implantation.

In all cases, the HAV maintained normal architecture and function.

A representative image is shown below, taken 50 months post-implantation.

Proximal and distal anastomoses of HAV with recipient’s vasculature are noted, as is the scale bar on the right-hand side of each image.

The image presents two views of the same subject, and shows uniform HAV diameter along the length of the implant.

A CT Angiogram from a V002 Subject at 51 months after HAV implantation

Patients in the V002 trial are currently in long-term follow-up out to ten years.

For the V002 trial, six-year long-term follow-up data were compiled in March 2021, which confirmed durability of the HAV in the arterial circulation.

For HAV patients in the V002 trial, there were also no reports of conduit infections, and no reports of amputations of the operative limb.

Long-term results from V002 Phase II study in PAD

Result from V002

Phase 2 Trial in PAD

(as of April 2021)

Pre-Op 1 yr 2 yr 3 yr 4 yr 5 yr 6 yr Avg

Secondary Patency — 84% 74% 73% 66% 60% 60% —

Ankle-Brachial Index (median) 0.64 0.90 0.96 — 1.07 0.98 0.94

HAV Infection Rate — 0% 0% 0% 0% 0% 0% 0%

The V004 trial enrolled 15 subjects in the United States, with the 12-month follow-up of the last enrolled patient occurring in December 2020.

Patients in the V004 trial included Rutherford 4 and 5 subjects, with severe, debilitating limb ischemia.

(Rutherford 4 and 5 patients are classified as patients with pain at rest due to limb ischemia (stage 4), and those patients suffering tissue loss in the limb as a result of ischemia (stage 5)).

In addition, enrollment in V004 required that no autologous vein be available for bypass.

Hence, the subjects enrolled in the V004 trial had severe and debilitating limb ischemia due to PAD and had no autologous vein that was suitable for lesion bypass and revascularization.

12-month results from V004 Phase II study in PAD

Result from V004 Trial (as of April 2021)

Pre-Op 6 mos 12 mos

Secondary Patency — 86% 64%

Ankle-Brachial Index (median) 0.51 0.85 0.90

Rate of Amputation — 0% 0%

VascuQol Quality of Life Assessment 3.1 5.6 5.9

In the V004 trial, HAV secondary patency was 86% at 6 months, and 64% at 12 months.

While lower than patency values observed in the V002 trial, patients in the V004 trial had more severe PAD, which is associated with poorer arterial “run-off” and higher propensity for conduit occlusion.

Assessment of Quality of Life by the validated VascuQol assessment demonstrated an increase in overall quality of life for V004 patients at 6 and 12 months.

In addition, ankle-brachial index, a measurement of blood pressure in the operative limb, was increased at 6 and 12 months.

There were no infections of the HAV reported in the V004 trial, despite the severity of the PAD and the often-associated tissue infection that can accompany this disease.

There were zero reports of clinical HAV rejection.

Lastly, there were zero reported amputations of any operative limb in the first 12 months of follow-up.

The SAEs reported for the HAV in our V002 and V004 Phase II clinical studies in PAD in 35 subjects, a patient population which typically has a high prevalence of existing medical conditions, are summarized in the table below.

SAEs Reported in V002 and V004 Phase II Clinical Studies in PAD

Description of SAE Number of SAEs

(% of total subjects)

Number of subjects in V002 and V004 studies

Arterial bypass thrombosis

Anastomotic stenosis

Graft Thrombosis

Vascular Graft Complication

Published literature reports of patients with Rutherford stage 4 and 5 PAD and no autologous vein available for revascularization show that outcomes can include amputation.

For Rutherford 4,5 patients with no vein and no revascularization procedure, amputation rates at 6 months are reported at 31%.

For stage 4,5 patients who do undergo saphenous vein revascularization, the amputation rate at one year is approximately 10%.

The lack of amputation for stage 4,5 patients in the V004 trial at one year, none of whom had saphenous vein for revascularization, supports the use of the HAV in severe PAD.

Examples of the Use of Our 6 millimeter HAVs in Expanded Access Cases

The FDA has granted use of the HAV in 17 special expanded access cases through December 31, 2021.

Each of these compassionate use cases was conducted under an individual, investigator-initiated IND with the FDA.

Two cases are highlighted below.

70-year-old with Critical Limb Ischemia

The patient is a 70-year-old male with critical limb ischemia and no vein available to perform a bypass, as the vein was previously used for a CABG.

He underwent a successful bypass with the HAV.

Imaging at one year demonstrated a patent graft.

42-year-old with Infected Dacron Graft

An HAV was used in a 42-year-old female to replace an 8 mm Dacron iliac artery bypass graft that had become infected.

The patient refused harvesting of the femoral vein for reconstruction and requested the HAV.

The patient was seen at one, three, six, nine, and 12 months after HAV implantation.

At all visits, the HAV appeared normal with unobstructed patency.

Flow and velocities were normal.

At three months, the patient was released to full activity.

At six and 12 months, the graft was functioning well.

At one-year imaging, the HAV was patent and appeared remarkably similar to the patient’s native blood vessels.

The patient had no signs of infection in the HAV and continues to have no limitations or complications during normal activity or exercise.

Preclinical Pipeline

Pancreatic Islet Transplantation for Type 1 Diabetes (“Biovascular Pancreas”)

The Biovascular Pancreas (“BVP”) is a modification of Humacyte’s HAV product, leveraging the HAV to deliver therapeutic cells to within close proximity of the patient’s bloodstream.

We believe that the HAV extracellular matrix material is both highly biocompatible, as evidenced by adaptive cellular repopulation after implantation, and also highly angiogenic, as evidenced by extensive formation of microvessels surrounding the HAV in vivo.

These attributes mean that the HAV may serve as a suitable conduit for delivering large numbers of therapeutic cells to a patient.

Pancreatic islets, which sense blood glucose and respond by secreting insulin, are destroyed by an auto-immune attack in patients with Type I diabetes.

The outer surface of our 42cm HAV has sufficient surface area to accommodate a monolayer of approximately 800,000 human pancreatic islets, which is approximately the number in an entire adult pancreas, and can reverse diabetes and restore glucose control.

We have performed mathematical modelling studies that predict, we believe, that a 42cm HAV could maintain viability of a therapeutic number of islets after implantation of the HAV into the arterial bloodstream, or after implantation as an AV conduit similar to that used for hemodialysis access.

Bioreactor experiments have confirmed these mathematical conclusions.

Furthermore, we have implanted rat-sized BVPs into the aortas of diabetic rats, and observed that the BVP could restore normal glucose levels in all treated animals, while control animals (“No Flow” in red in figure below) did not restore glucose control.

Studies in large animal models are planned as the next step in the development of this product candidate.

Coronary Artery Bypass Graft (CABG)

Evaluation of 3- and 4mm diameter HAVs for coronary artery bypass is ongoing at Humacyte.

Our initial pilot studies have included the use of our engineered vessels for CABG in canines, demonstrating functional patency and adequate blood flow for up to one month.

To further evaluate the utility and durability of the HAV in a large animal model, we have initiated a preclinical study at Duke University to evaluate the use of our small diameter HAV for CABG in adult primates (baboons).

The goal of this study is to assess patency and function for six to 12 months, as well as host responses and cellular remodeling.

We anticipate that this study will provide sufficient in vivo data to support an IND filing for a Phase I clinical trial in adult CABG.

As of December 31, 2021, we have implanted a 3.5mm HAV CABG from the aorta to the left anterior descending coronary artery in five baboons.

HAVs are followed by ultrasound imaging of the heart, and angiographic imaging of the conduits.

In January 2022, results from this preclinical study were presented at Advanced Therapies Week where we reported that the HAV maintained patency and exhibited host-cell remodeling and regeneration in the non-human primate model.

Before (left) and after (right) implantation of HAV CABG in baboon

Pediatric Heart Surgery:

Modified Blalock-Taussig-Thomas (mBTT) Shunt

Tetrology of Fallot is a relatively common congenital heart defect, that is often treated using a modified Blalock-Taussig-Thomas (“mBTT”).

To support a potential future IND filing with the FDA, we have evaluated the use of our HAV as an mBTT shunt for up to six months in juvenile primates at the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio.

BT Shunt Implant Schematic

In November 2021, the results for this preclinical study were presented at the American Heart Association’s Scientific Sessions 2021 meeting.

In this study, five non-immunosuppressed juvenile primates were surgically implanted with the 3.5mm diameter HAVs as mBTT shunts.

The 3.5mm HAVs were implanted into primates as mBTT shunts using standard surgical techniques, and the animals were studied for three to six months.

Each of the HAVs remained parent during the study and exhibited repopulation with vascular cells.

Two of the primates showed a stronger xenogeneic to the human HAV material.

The 3.5mm diameter HAV has smaller product dimensions but is manufactured using a similar process as Humacyte's 6mm HAV system currently being evaluated in clinical trials in vascular trauma, AV access for hemodialysis, and PAD.

We believe that the production of the functional 3.5mm HAV is indicative of the potentially broad application of our proprietary bioengineered tissue platform and manufacturing processes.

Imaging of 3.5mm HAV mBTT shunt in juvenile primate followed for 6 months

Engineered Trachea for Treatment of Severe Airway Injuries

Each year in the United States, approximately 4,000 operations are performed to repair or reconstruct the trachea or mainstem bronchi.

But unlike most other connective tissues in the body — such as blood vessel, bone, skin and tendon — there currently are no replacements for tracheal tissue that are in widespread clinical use.

For long tracheal or bronchial defects, some sort of tracheal replacement is often needed, yet none exists currently.

The lack of a functional tracheal conduit commits patients to, sometimes, slow suffocation.

We have modified the HAV production process to enable the embedding of a biocompatible medical-grade stent within the wall of the engineered vessel.

Combining a non-degradable stent with the degradable polymer scaffold used for HAV production results in a composite scaffold that can be seeded with smooth muscle cells and grown in culture.

After decellularization, the engineered trachea consists of the extracellular matrix contained in the HAV, along with an embedded stent that prevents the collapse of the engineered airway with inspiration or neck movements.

Summary of Process to Generate Engineered Tracheas

In models where engineered tracheas were implanted into rats and non-human primates, we have observed that the implants repopulate with cells from the host, including cuboidal respiratory epithelium that lines the native airway progressively from two to eight weeks after implantation.

We have further observed that the engineered tracheas can function out to two months.

Future studies in large animal models are planned.

Photograph (A) of Implantation of Engineered Trachea into Non-Human Primate Airway;

Microscope Imaging of Cells Repopulating the Trachea after 2 and 8 weeks (B, C)

Engineered Whole Lung Organs

End-stage lung disease is the fourth leading cause of death in the U.S., and lung transplantation remains severely limited by donor organ shortages.

Niklason’s laboratory at Yale University has pioneered the development of using decellularized native lungs, combined with targeted recellularization of the lung scaffolds within biomimetic bioreactors, to produce whole lungs that are capable of exchanging gas.

Gas exchange for several hours has been observed in studies in rodents.

Efforts to scale-up the technology to human-sized organs are ongoing.

Structure of Lung, Scaffold for Lung Engineering, and Implanted Engineered Lung

Manufacturing

We have developed a novel paradigm for manufacturing human tissues that mimics key aspects of human physiology.

Recognizing that commercial scale production capacity of bioengineered tissue has been non-existent, we prioritized the development of a scalable, reproduceable, commercial biomanufacturing process.

At our 83,000 square foot manufacturing facility in Durham, North Carolina, we have industrialized this concept and created a scalable modular manufacturing process that enables us to engineer our HAVs in commercial quantities in a system designed for cGMP compliance.

The system used in our clinical trials since 2016, including all Phase III trials, utilizes a single tray within one growth drawer holding ten HAVs per batch.

These batches were manufactured at a contract manufacturer.

The current, commercial-scale LUNA200 system utilizes 20 growth drawers holding ten HAVs each for a total of 200 HAVs per batch.

This system is planned to be utilized for ongoing Phase III trials and for subsequent anticipated commercial launches once approved.

Our manufacturing process utilizes our LUNA200 system, consisting of 20 “growth drawers.” Each growth drawer is capable of producing ten 42cm HAVs and each HAV remains contained within an individual bioreactor bag.

Inside a LUNA200, a closed tubing network connects all 20 growth drawers as well as the ten bioreactor bags in each drawer, allowing the entire system to share cells and nutritive media.

In this way, a single LUNA200 can produce up to 200 HAVs per batch while maintaining the critical operating parameters that direct growth, creating a gross capacity of approximately 900 HAVs per system annually.

A thorough comparability assessment was performed to evaluate HAV batches produced in the single drawer system and used in Phase III studies versus the 20-drawer LUNA200 system.

The study assessed 22 separate comparisons on the identity, strength, quality, purity, and potency of the HAV product.

In this study, we observed that HAVs produced in the LUNA200 system were comparable to HAVs used in our Phase III trials.

Thus far in this trial we have observed comparable safety profile between HAV used in previous studies and the HAV manufactured in the LUNA200 commercial system.

The results of the comparability assessment and the 30-day results from the V011 crossover study were submitted to the FDA.

In 2021, the FDA authorized the use of HAVs produced in the commercial LUNA200 system to supply our ongoing clinical trials.

We plan to also use the LUNA200 system for anticipated commercial launches of the HAV if it is approved.

We have designed the LUNA200 to have the ability to produce HAVs in diameter sizes from 3mm to 10mm and lengths from 10cm to 42cm, making the equipment suitable for the varied array of product candidates in our pipeline.

We intend to introduce a 13cm HAV line extension after commercial launch of the 42cm HAV.

Using our existing LUNA manufacturing equipment, we can generate 400 13cm HAVs per batch.

Our modular manufacturing platform can be scaled without impacting the operating parameters that support the HAV growth process.

We have designed our manufacturing system to be functionally closed, to utilize single-use disposable materials with aseptic connections, and to be fully automated.

Modular Manufacturing Platform Allows for Production of Multiple Product Lengths Using the Same Equipment

We currently have eight LUNA200 systems installed, commissioned and qualified in our manufacturing facility, creating an annual gross HAV capacity of approximately 7,200 HAVs.

Our manufacturing facility contains space to increase capacity in future years to approximately 40 LUNA200 systems in total.

As we continue to expand production, we believe that we will have the ability to take advantage of economies of scale and reduce production costs.

The initiation and pace of the expansion of vessel capacity will be determined based on our assessment of market opportunity.

We initiate HAV production using primary human aortic vascular cells from a working cell stock (“WCS”) that is isolated from FDA-compliant donor tissues and cryopreserved.

The WCS vials are stored at two separate qualified facilities to mitigate the risk of single site storage.

We qualify all new WCSs for use in HAV manufacturing utilizing biochemical and gene expression assays.

Each qualified primary isolation can produce approximately 500,000 to one million HAVs.

The WCS expanded using traditional cell culture techniques, and the cells are transferred onto a biocompatible, biodegradable polymer mesh within a flexible, single-use bioreactor bag.

Cells inoculated onto this tubular mesh are cultured utilizing a proprietary culture medium and subjected to cyclic mechanical stretch for a period of approximately eight weeks.

During this period, the cells proliferate and build extracellular matrix while the polymer mesh degrades.

The resulting bioengineered vessel is comprised of the aortic vascular cells and their deposited extracellular matrix.

After completion of the culture period, we decellularize the bioengineered vessel using a proprietary combination of salts, enzymes and detergents, followed by numerous washes in excipient grade neutral pH buffered saline.

The resulting HAV retains the human extracellular matrix constituents and, therefore, the biomechanical properties of the bioengineered vessel, but cells and cellular components, which could induce a foreign body response or immune rejection following implantation, are removed.

After decellularization, our HAVs are packaged for distribution inside the same flexible bioreactor bag in which they were produced, with sterile phosphate buffered saline as the excipient.

Once the package is delivered to the operating room, the HAV is removed from the bioreactor bag by the surgical staff.

We source critical components and necessary raw materials from vendors that have been approved and qualified through our vendor management program.

SeraCare, which was subsequently acquired by LGC Clinical Diagnostics, Inc.

(“SeraCare”), is the current single source supplier of human plasma used in our manufacturing process and Confluent Medical Technologies, Inc.

(“Confluent”) is the current single source supplier of the polymer mesh we use.

We source custom, Humacyte-designed, pre-sterilized (gamma irradiated) assemblies and single-use tubing sets through multiple approved vendors.

We source bioprocess solutions, including culture media and decellularization buffers, from a division of Thermo Fisher Scientific, which has a second production site to provide redundant media/buffer production capacity.

We are in the process of developing redundant vendors for all critical materials and we manage all vendor changes through a robust change control process.

Supply Agreement with SeraCare

In January 2014, we entered into a supply agreement with SeraCare for the supply of human plasma, which was amended in October 2018.

We refer to the supply agreement, as amended, as the SeraCare Agreement.

Under the SeraCare Agreement, we agreed to purchase at least a substantial majority of our human plasma requirements from SeraCare.

In the event SeraCare is unable to fulfill our requirements, and subject to certain conditions, we may engage another plasma supplier during the period in which SeraCare is unable to fulfill our requirements.

The SeraCare Agreement is subject to annual price modifications in the case of significant changes in SeraCare’s cost of raw materials, with any modification to be determined at least three months prior to the end of the relevant year.

The initial term of the SeraCare Agreement expires on October 12, 2023, but automatically extends for subsequent one-year periods unless terminated by either party at least 18 months prior to the end of the initial term.

Either party may terminate the SeraCare Agreement for uncured material breach or for the insolvency of the other party at any time.

In addition, either party may terminate the SeraCare Agreement without cause upon 12 months’ written notice.

We may also terminate the agreement in the event of certain supply interruptions.

Each party also agreed to indemnify the other against certain third-party claims up to a specified cap.

Supply Agreement with Confluent

In August 2015, we entered into an agreement for the supply of polymer mesh, which we refer to as the mesh supply agreement, with Biomedical Structures LLC.

Biomedical Structures’ rights and obligations under the mesh supply agreement were subsequently assigned to Confluent in connection with Confluent’s acquisition of Biomedical Structures in 2016.

In 2020, the agreement was amended to align with the growth expected with the transition to commercial distribution following FDA approval.

Pursuant to the mesh supply agreement, the price of polymer mesh we purchase from Confluent is subject to potential adjustment if Confluent’s cost of raw materials increases above a specified threshold pursuant to good faith negotiations from both parties, which negotiation Confluent may not request more than once in a 12-month period.

The 2020 amendment also provided volume driven discounts.

Confluent is obligated to partner with Humacyte in order to establish redundant facilities for the manufacture of the polymer mesh at established contractual volume thresholds.

The amended mesh supply agreement has a term of three years, which can be automatically extended for subsequent one-year periods and will continue to do so unless either party provides notice of non-renewal at least 120 days prior to the end of the then-current term or otherwise terminates in accordance with the agreement.

We and Confluent are each also permitted to terminate the mesh supply agreement for convenience, however Confluent must provide us with at least 365 days written notice and we are obligated to provide 180 days’ notice, prior to such a termination.

In addition, each party is permitted to terminate the mesh supply agreement for an uncured material breach by the other party following failure to remedy the breach during a sixty-day cure period.

Both parties have agreed to indemnify one another for certain third-party claims.

Commercialization Strategy Within United States and for Earlier-Stage Pipeline Programs

For our vascular repair and replacement applications of our technology, including renal replacement therapy for dialysis access, the treatment of PAD, and the treatment of vascular trauma, we have retained the right to commercialize our HAV within the United States, and expect to commercialize the HAV through a combination of our own direct sales and marketing team combined with our partnership with Fresenius Medical Care described below.

We plan to own end-to-end commercialization while pursuing collaborations with appropriate strategic partners who have established distribution channels for supplying customer care centers.

Our first expected market launch, in the treatment of vascular trauma, is a highly concentrated market of approximately 190 Level I Trauma Centers that may be reached with a small field sales forces of no more than 20 representatives.

Many of the major trauma centers already have familiarity with our HAV product candidate through their participation in our clinical trials.

Our sales effort will include dual targeting of surgeons to create pull-through demand and hospital administration (trauma center Value Analysis Committees) to assure adoption and uptake of the HAV in vascular trauma.

We expect that the large market potential of earlier-stage applications of our technology platform such as CABG and biovascular pancreas for diabetes will provide additional collaboration opportunities, and we expect explore strategic partnerships for these product candidates as preclinical and clinical results providing additional proof of concept are generated.

Distribution Agreement with Fresenius Medical Care

We entered into a distribution agreement with Fresenius Medical Care in June 2018 which, as amended as of February 16, 2021, granted Fresenius Medical Care and its affiliates exclusive rights to develop outside the United States and European Union (the “EU”) and commercialize outside of the United States our 6 millimeter x 42cm HAV and all improvements thereto, and modifications and derivatives thereof (including any changes to the length, diameter or configuration of the foregoing), for use in vascular creation, repair, replacement or construction, including renal replacement therapy for dialysis access, the treatment of peripheral arterial disease, and the treatment of vascular trauma, but excluding coronary artery bypass graft, pediatric heart surgery, or adhering pancreatic islet cells onto the outer surface of the distribution product for use in diabetic patients.

Within the United States, Fresenius Medical Care will collaborate with Humacyte in its commercialization of the product in the field, including adoption of the distribution product as a standard of care in patients for which such use is supported by clinical results and health economic analyses.

We are responsible for developing and seeking regulatory approval for the distribution product in the field in the United States.

For countries outside the United States, the parties agreed to use commercially reasonable efforts to satisfy certain agreed minimum market entry criteria for the distribution product in the field in such country.

For the EU, once such criteria have been satisfied for the applicable country, or if the parties otherwise mutually agree to obtain regulatory

approval for the distribution product in the field in the applicable country, we agreed to use commercially reasonable efforts to obtain such regulatory approval (other than pricing approval), and Fresenius Medical Care agreed to use commercially reasonable efforts to obtain the corresponding pricing approval.

For the rest of the world (i.e., outside the United States and the EU), once such criteria have been satisfied for the applicable country, or if the parties otherwise mutually agree to obtain regulatory and pricing approval for the distribution product in the field in the applicable country, Fresenius Medical Care agreed to use commercially reasonable efforts to obtain such approvals, and we agreed to use commercially reasonable efforts to support Fresenius Medical Care in its efforts.

Under the distribution agreement, we grant an exclusive, sublicensable license to Fresenius Medical Care under the patents, know-how and regulatory materials controlled by us during the term to commercialize the distribution product in the field outside the United States, subject to our retained rights to carry out our obligations under the distribution agreement.

We also grant a non-exclusive, sublicensable license to Fresenius Medical Care under the patents, know-how and regulatory materials controlled by us during the term to develop the distribution product in accordance with the terms of the distribution agreement.

In addition, we grant to Fresenius Medical Care, among other things, a perpetual, irrevocable, non-exclusive sublicensable license under the patents and know-how that primarily relate to the distribution product or its manufacture and that were created, conceived or developed solely or jointly by or on behalf of Fresenius Medical Care in the performance of its activities under the distribution agreement.

The distribution agreement provides that we will own all know-how and patents that primarily relate to the distribution product or its manufacture that are created, conceived or developed by or on behalf of either party in the performance of activities under the distribution agreement.

Ownership of all other know-how, patents, materials and other intellectual property created, conceived or developed during the performance of activities under the distribution agreement will be determined in accordance with U.S.

patent laws for determining inventorship.

We are obligated to make payments to Fresenius Medical Care based on a share of aggregate net sales by or on behalf of us of the distribution product in the United States in the field.

Such revenue-share payments will be a percentage of net sales in the low double digits, without regard to the calendar year in which such net sales are attributable, until such time that we have paid to Fresenius Medical Care a certain total amount, at which time the revenue-share will decrease to a percentage of net sales in the mid-single digits.

The amounts that Fresenius Medical Care will be obligated to pay us under the distribution agreement for sales of the distribution product in the field outside of the United States will vary.

Fresenius Medical Care agreed to pay us initially, on a country-by-country basis for sales outside of the United States, the amount equal to the average cost of manufacturing our distribution product plus a fixed dollar amount per unit.

Following a specified period, on a country-by-country basis outside of the United States, Fresenius Medical Care will pay us a fixed percentage of net sales for each unit sold in such country, such that the Company will receive more than half of such net sales.

The distribution agreement will generally continue on a country-by-country basis until the later of the tenth anniversary of the launch date of the distribution product in the relevant country or (b) the expiration of the last-to-expire valid claim of specified patents in such country.

Each party is permitted to terminate the distribution agreement for insolvency of, or, under certain circumstances, including various cure periods, material breach by the other party.

Subject to a cure period, Fresenius Medical Care may also terminate the distribution agreement in its entirety or on a country-by-country basis (i) for certain withdrawals of regulatory approval or (ii) for termination or expiration of any of our in-licenses that is necessary for the exercise of Fresenius Medical Care’s rights, or the satisfaction of its obligations, under the distribution agreement.

In addition, Fresenius Medical Care may terminate the distribution agreement for convenience on a country-by-country basis upon not less than 12 months’ written notice to us, although Fresenius Medical Care is not permitted to give such notice prior to the end of the second year following launch of the distribution product in such country.

Each party is required to indemnify one another for certain third-party claims.

Third-Party Reimbursement

We anticipate that coverage and reimbursement by the Centers for Medicare and Medicaid Services (“CMS”) and private payors will be essential for most patients and health care providers to afford our treatments, particularly in the applications of renal replacement therapy for dialysis access and the treatment of PAD.

Accordingly, sales of our products will depend substantially, both domestically and abroad, on reimbursement by government authorities, private health coverage insurers and other third-party payors.

Our strategy around HAV reimbursement focuses on achieving alignment and agreement from CMS on coding and payment pathways;

both are critical to influencing and achieving optimal reimbursement payment from private payor sources.

Therefore, Humacyte continues to develop a comprehensive reimbursement strategy including CMS, private payors, and other key stakeholders to ensure a clear and sustainable reimbursement path for all HAV product opportunities.

We are pursuing a dual regulatory and legislative reimbursement strategy to ensure separate Medicare payment for the HAV at an appropriate price.

The regulatory strategy includes (1) engaging CMS political and career staff directly on coverage, payment, and coding followed by (2) submission of formal applications in these areas once FDA approval is obtained.

Currently, no RMAT tissue engineered product has established coverage and reimbursement by CMS, and it is difficult to predict what CMS will decide with respect to coverage and reimbursement for fundamentally novel products.

See “Risk Factors — Risks Related to the Development and Commercialization of Our Product Candidates” for further information.

Even if we receive marketing approval for our HAVs, there is uncertainty with respect to third-party coverage and reimbursement of our HAVs.

They may also be subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, any of which could harm our business, prospects, operating results and financial condition.

Intellectual Property

We strive to protect and enhance the proprietary technology, inventions and improvements that are commercially important to the development of our business, including seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties.

We also rely on trade secrets relating to our proprietary technology platform and on know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen and maintain our proprietary position that may be important for the development of our business.

We additionally may rely on regulatory protection afforded through data exclusivity, market exclusivity and patent term extensions where available.

Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for commercially important technology, inventions and know-how related to our business, defend and enforce our patents, preserve the confidentiality of our trade secrets, and operate without infringing the valid and enforceable patents and proprietary rights of third parties.

As of December 31, 2021, our patent estate is comprised of 15 families of patents.

Of these families, nine are solely owned by Humacyte, one is jointly owned by Humacyte and Global Life Sciences Solutions USA LLC, one is jointly owned by Humacyte and Yale University, two are exclusively licensed to Humacyte from Duke University and two are exclusively licensed to Humacyte from Yale University.

For more information regarding these license agreements, see “— License Agreement with Duke University” and “— License Agreements with Yale University.”

Our 15 families of patents are comprised of:

(i) eight issued U.S.

patents, 64 foreign patents in Austria, Belgium, Canada, China, Cyprus, Denmark, France, Germany, Hong Kong, Hungary, Ireland, Italy, Japan, Liechtenstein, Netherlands, Spain, Sweden, Switzerland, Turkey, and the UK, five pending U.S.

non-provisional patent applications, one pending PCT patent application and two pending foreign applications in Europe and Hong Kong, which are solely owned by us,

(ii) three issued U.S.

patents, 18 issued foreign patents in Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Japan, Liechtenstein, Netherlands, Spain, Sweden, Switzerland, Turkey, and the UK, one pending U.S.

non-provisional patent application, and three pending foreign patent applications in Europe and Canada, which we co-own, and

(iii) two issued U.S.

patents, 23 issued foreign patents in Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Liechtenstein, Netherlands, Spain, Sweden, Switzerland, Turkey, and the UK, one pending U.S.

non-provisional patent application, and seven pending foreign patent applications in Australia, Canada, Europe, Japan, China, and Hong Kong, which we exclusively license.

Many of these patents and patent applications generally relate to the scaffolds used to make our vessels, the composition of our vessels, and systems and methods of manufacturing our vessels.

Excluding any patent term adjustment or patent term extension, the U.S.

patent relating to the scaffold used to make our vessels expires in 2032, the U.S.

patents relating to the composition of our vessels expire in 2032 and the U.S.

patents relating to the systems and methods of manufacturing our vessels expires in 2032.

patent relating to the entangler machinery used to make tubular scaffolds expires in 2035.

Included in our patent portfolio are three pending, Humacyte-owned non-provisional applications relating to the manufacturing of engineered tissues at commercial scale.

If these three non-provisional applications are allowed, such additional patents issuing therefrom would be expected to expire around 2040.

As with other biotechnology and pharmaceutical companies, our ability to maintain and solidify our proprietary and intellectual property position for our product candidates will depend on our success in obtaining effective patent claims and enforcing those claims if granted.

However, our owned and licensed pending patent applications, and any patent

applications that we may in the future file or license from third parties, may not result in the issuance of patents.

For more information, see “Risk Factors — Risks Related to Our Intellectual Property.”

We have also registered trademarks for use in connection with our products.

These include registrations for HUMACYL™ in the United States, Europe, Australia, Canada, China, and Israel;

HUMAGRAFT™ in Australia, China, Europe, and Israel;

HUMAPASS™ in Europe, Australia, and Israel;

and HUMACYTE, in the United States, Europe, Australia, Canada, and Israel.

We may pursue additional registrations for future products in markets of interest.

In addition to the above, we have established expertise and development capabilities focused in the areas of preclinical research and development, manufacturing process scale-up, cGMP manufacturing, quality control, quality assurance, compliance, regulatory affairs and clinical trial design and execution.

We believe that our focus and expertise will help us develop and expand technology-based applications leveraging our proprietary intellectual property.

Finally, we rely, in some circumstances, on trade secrets to protect our technology.

We seek to protect our proprietary technology and processes, in part, by entering into confidentiality agreements with our employees, consultants, scientific advisors and contractors.

We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems.

In addition to the intellectual property that we have developed internally, we license rights to certain intellectual property that is material to our business prospects.

We have summarized our material license agreements below.

License Agreement with Duke University

In March 2006, we entered into a license agreement with Duke University (“Duke”), which was subsequently amended in 2011, 2014, 2015, 2018, 2019 and January 2022.

We refer to the license agreement, as amended, as the Duke License Agreement.

Under the Duke License Agreement, Duke granted us a worldwide, exclusive, sublicensable license to certain patents related to decellularized tissue engineering, which we refer to as the patent rights, as well as a non-exclusive license to use and practice certain know-how related to the patent rights.

The relevant licensed patent on decellularization of tissue expired in 2021.

We have agreed to use commercially reasonable efforts to develop, register, market and sell products utilizing the patent rights, which we refer to as the licensed products.

Any services provided to a third party utilizing licensed products are referred to as licensed services.

We have also agreed to meet certain benchmarks in our development efforts, including as to development events, clinical trials, regulatory submissions and marketing approval, within specified timeframes.

Under the Duke License Agreement, Duke retains the right to use the patent rights for its own educational and research purposes, and to provide the patent rights to other non-profit, governmental or higher-learning institutions for non-commercial purposes without paying royalties or other fees.

In connection with our entry into the Duke License Agreement, we granted equity consideration to Duke in the form of 52,693 shares of our post-Merger common stock.

Under the Duke License Agreement, we have also agreed to pay Duke:

a low single-digit percentage royalty on eligible sales of licensed products and licensed services, plus a low double-digit percentage of any sublicensing revenue;

an annual minimum royalty beginning in 2012, which increases in the calendar year immediately following the first commercial sale of licensed products or licensed services (whichever occurs first);

and an additional amount in license fees, as certain scientific milestones are met.

The Duke License Agreement remains effective until the latter of (i) the last of the patent rights expires or (ii) four years after our first commercial sale, unless earlier terminated.

Either party may terminate the agreement for fraud, willful misconduct or illegal conduct, or uncured material breach.

Duke may terminate the agreement if we become insolvent.

Duke may also terminate the license, convert the license into a non-exclusive license or seek assignment of any sublicense if we fail to reach diligence milestones within the applicable time period.

If we abandon any claim, patent or patent application, our rights under the license with respect to such patent rights will be terminated in the territory in which we abandon such rights.

We may terminate the Duke License Agreement unilaterally upon three months’ prior notice to Duke.

We agree to indemnify Duke against certain third-party claims.

License Agreements with Yale University

Large Diameter HAV

In August 2019, we entered into a license agreement with Yale University (“Yale”) that granted us a worldwide license to the patents jointly owned with us related to tubular prostheses which are large diameter versions of our vessels, which may or may not contain a stent.

The license granted under the agreement is exclusive in the field of engineered urinary conduits, engineered tracheae/airways and engineered esophagi, except that it is subject to Yale’s non-exclusive right, on

behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes.

We have agreed to use reasonable commercial efforts to develop and commercialize the licensed patents and any licensed products and methods, and to use reasonable efforts to make the licensed products available to patients in low and low-middle income countries.

We are also obligated to provide Yale periodically an updated and revised copy of our plan, which must indicate progress of our development and commercialization.

We may also sublicense our rights without Yale’s prior written consent, but such sublicense is subject to certain conditions.

In connection with our entry into the Yale License Agreement, we paid Yale an upfront cash fee of less than $0.1 million.

We have also agreed to pay to Yale:

an annual maintenance fee, increasing between the first anniversary of the agreement until the fifth anniversary up to a maximum of less than $0.1 million per year;

milestone payments upon achievement of certain regulatory and commercial milestones of $0.2 million and $0.6 million for this license;

a low single-digit percentage royalty on worldwide net sales, subject to reductions for third-party license fees;

and a low double-digit percentage of sublicensing income.

If we or any of our future sublicensees bring a patent challenge against Yale or assist another party in bringing a patent challenge against Yale, the license fees described above will be subject to certain increases and penalties.

The agreement expires on a country-by-country basis on the date on which the last of the patents in such country expires, lapses or is declared invalid.

Issued patents and additional patents issuing from this licensed portfolio will expire no earlier than 2032, and the term of each patent may be extended by patent term adjustment, patent term extension, or foreign equivalents thereof.

10,172,707 will expire no earlier than 2035.

Yale may terminate the agreement if we fail to (i) provide written diligence reports, (ii) provide a commercially reasonable diligence plan, (iii) implement the plan in accordance with the obligations under the agreement, or (iv) reach certain research and development milestones within the scheduled timeframe set forth in the agreement;

however, any such termination right would be limited in scope to the country or countries to which such failure relates.

Yale may also terminate for our non-payment, uncured material breach, failure to obtain adequate insurance, bringing or assisting in bringing of a patent challenge against Yale, abandonment of the research and development of our product or insolvency.

We may terminate the license agreement (i) on 90 days’ prior written notice to Yale, provided we are not in breach of the license agreement and have made all required payments to Yale thereunder and (ii) on written notice to Yale following an uncured material breach.

Under certain circumstances, Yale may, at its option, convert the exclusive license to a non-exclusive license if we decline to initiate certain infringement or interference proceedings with respect to the licensed patents.

We have agreed to indemnify Yale against certain third-party claims.

Small Diameter HAV Coating

In February 2014, we entered into a license agreement with Yale that granted us a worldwide license to the patents related to coatings for small-diameter vessels to inhibit clotting.

The license granted under the agreement is exclusive in the field of engineered vascular tissues and tissues and extracellular matrix-based implants used for vascular repair, reconstruction and replacement (provided that all uses are vascular tissues within the range of 1-12mm in diameter), except that it is subject to Yale’s non-exclusive right, on behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes.

We are also obligated to provide Yale periodically an updated and revised copy of our plan, which must indicate progress of our development and commercialization.

We may also sublicense our rights without Yale’s prior written consent, but such sublicense is subject to certain conditions.

In connection with our entry into the Yale License Agreement, we paid Yale an upfront cash fee of less than $0.1 million.

We have also agreed to pay to Yale:

an annual maintenance fee, increasing between the first anniversary of the agreement until the fifth anniversary up to a maximum of less than $0.1 million per year;

milestone payments upon achievement of certain regulatory and commercial milestones of $0.2 million and $0.6 million for this license;

a low single-digit percentage royalty on worldwide net sales, subject to reductions for third-party license fees;

and a low double-digit percentage of sublicensing income.

The agreement expires on a country-by-country basis on the date on which the last of the patents in such country expires, lapses or is declared invalid.

Issued patents and additional patents issuing from this licensed portfolio will expire no earlier than 2034, and the term of each patent may be extended by patent term adjustment, patent term extension, or foreign equivalents thereof.

however, any such termination right would be limited in scope to the country or countries to which such failure relates.

Our rights under the license agreement will also terminate automatically with respect to a patent application or patent within the licensed patents in a specified country if, upon receipt of written notice from Yale, we do not agree to pay the patent filing, prosecution and maintenance fees incurred by Yale for such patent applications or patents in the specified country.

We have agreed to indemnify Yale against certain third-party claims.

Biovascular Pancreas

In August 2019, we entered into a license agreement with Yale that granted us a worldwide license to its patents related to a biovascular pancreas.

The license granted under the agreement is exclusive in the field of acellular vascular tissues that deliver pancreatic islet cells to patients, except that it is subject to Yale’s non-exclusive right, on behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes.

We are also obligated to provide Yale periodically an updated and revised copy of our plan, which must indicate progress of our development and commercialization.

We may also sublicense our rights without Yale’s prior written consent, but such sublicense is subject to certain conditions.

In connection with our entry into the Yale License Agreement, we paid Yale an upfront cash fee of less than $0.1 million.

We have also agreed to pay to Yale:

an annual maintenance fee, increasing between the first anniversary of the agreement until the fifth anniversary up to a maximum of less than $0.1 million per year;

milestone payments upon achievement of certain regulatory and commercial milestones of $0.1 million and $0.2 million for this license;

a low single-digit percentage royalty on worldwide net sales, subject to reductions for third-party license fees;

and a low double-digit percentage of sublicensing income.

If we or any future sublicensees bring a patent challenge against Yale or assist another party in bringing a patent challenge against Yale, the license fees described above will be subject to certain increases and penalties.

The agreement expires on a country-by-country basis on the date on which the last of the patents in such country expires, lapses or is declared invalid.

Patents issuing from this licensed portfolio will expire no earlier than 2039, and the term of each patent may be extended by patent term adjustment, patent term extension, or foreign equivalents thereof.

however, any such termination right would be limited in scope to the country or countries to which such failure relates.

We may terminate the license agreement (i) on 90 days’ prior written notice to Yale, provided we are not in breach of the license agreement and have made all required payments to Yale thereunder and on written notice to Yale following an uncured material breach.

Under certain circumstances, Yale may, at its option, convert the exclusive license to a non-exclusive license if we decline to initiate certain infringement or

interference proceedings with respect to the licensed patents.

We have agreed to indemnify Yale against certain third-party claims.

Despite the magnitude and critical nature of the diseases and conditions we are targeting, no significant advances in the open surgical market have been made in the last 35 years, and current treatment and products used in vascular repair, reconstruction and replacement suffer from various drawbacks.

The large majority of vascular repair, reconstruction and replacement procedures rely on either harvesting autologous veins or using synthetic grafts.

However, each method presents significant limitations as discussed below:

Autologous Veins

The harvest of autologous veins is a serious operation that can result in numerous complications, including infection, chronic pain, and limb swelling that severely impact the patient’s quality of life.

In addition, this procedure can often result in long recovery times, increased hospital stays, and increased risk of hospital readmission.

In order to obtain an autologous vein, such as a saphenous vein, for use in a surgical procedure, a second operation must be performed on the patient to harvest the vein.

The harvesting process must be completed before the bypass procedure occurs and can take significant time to complete, which increases costs related to the additional operative time and staff required to perform the operation.

Even if successful, the patient’s recovery time could increase as the patient must recover from two surgical procedures instead of one, further increasing morbidity and cost.

Additionally, a significant percentage of patients are not suitable for vein harvesting either due to vein or limb damage, limited vein supply from prior harvest, venous disease or the surgeon’s desire to preserve the vein for future coronary or other bypass procedures.

In acute trauma, the time to restore blood flow to injured limbs is delayed when a vein must be harvested from the patient, which puts the limbs at greater risk of reduced function or amputation.

For patients suffering from vascular trauma, some types of injury preclude the harvesting of autologous saphenous vein due to concomitant injuries of one or both legs.

Furthermore, time is required to prepare the vein harvest site and to remove the vein from the leg, which adds to ischemia time and can increase the risk of tissue and limb loss.

Rates of traumatic limb loss are strongly tied to ischemia time, and therefore rapid revascularization using an off-the-shelf HAV conduit may decrease ischemia time and lead to better outcomes.

The use of autologous vein for creating an AV fistula for use in hemodialysis is often limited by vein size and location.

The vast majority of veins must go through a process of enlargement, known as maturation, prior to use for hemodialysis.

For approximately 40% of patients receiving fistulae, the vein does not mature sufficiently to allow for hemodialysis even after six months.

Even in patients having adequate veins for fistula creation, the fistula often becomes large, tortuous and disfiguring and can be at risk for sometimes fatal rupture.

Synthetic Grafts

Use of synthetic materials, such as ePTFE and Dacron, while widely available, have known complications, such as continuous chronic risk of infection and clotting inside the graft.

Risk of infection is significantly increased in acute battlefield and civilian injuries, as well as in contaminated wounds.

The body recognizes any synthetic materials as foreign and, therefore, can mount a host foreign body response following implantation.

Synthetic materials also have been shown to be inferior to autologous vein in resisting infection, and generally only are used for vascular repair when autologous vein is not an option.

In hemodialysis access, persistent puncture presents an ongoing risk of graft infection.

The annual risk of infection of ePTFE grafts in hemodialysis patients can be as high as 10% – 15% per patient-year.

Furthermore, gradual degradation of the non-healing ePTFE graft material caused by persistent needle punctures can eventually lead to graft failure.

In traumatic vascular injury, ePTFE grafts are generally contraindicated, due to the high rates of contamination of the wound that can lead to synthetic graft infection and failure.

Two lesser used products, cryopreserved human blood vessels, known as allografts, and animal-derived vessels, known as xenografts, also involve significant limitations.

Cryopreserved Blood Vessels

To eliminate the need for harvesting autologous vein, some surgeons use allogeneic vessels that have been previously harvested from cadavers and cryogenically preserved.

These allogeneic vessels are stored at -80 degrees Celsius and must be thawed prior to use, which can take up to 60 minutes.

The supply of cryopreserved vessels is limited by the number of cadaveric donors available, and the vessels are often non-uniform in size.

In addition, because the vessels contain human

cells from a donor, they can generate an immune rejection response that can lead to aneurismal degradation or catastrophic failure.

Furthermore, development of antibodies to the implanted cryopreserved human vessel frequently has a detrimental impact on the ability of the patient to receive a transplant in the future.

Cryopreserved blood vessels are only rarely used in the treatment of vascular trauma, due to the time required for procurement and thawing, and the high rates of rejection response.

Animal-Derived Vessels

Xenogeneic tissues, including cow, pig or sheep-derived vessels, are used less frequently in vascular surgery, in part due to the risk of thrombosis and structural deterioration over time.

The limited clinical data that are available for existing xenografts in vascular reconstruction indicates lower patency rates and higher incidence of complications when compared to autologous vein.

Xenografts are all chemically treated in efforts to minimize rejection to animal components, and therefore do not respond like living tissue.

Some of these products require rinsing to remove toxic chemicals used for storage.

We believe our HAVs combine the off-the-shelf availability of synthetic grafts with the regenerative capabilities of autologous vessels.

We believe these and other attributes have the potential to address unmet clinical needs in a range of disease states, including atherosclerosis, end-stage kidney disease, coronary artery disease, vascular trauma, pediatric congenital heart disease, airway disease, and others.

We believe that the HAV’s multiple key characteristics will drive rapid clinical adoption amongst surgeons and the broader healthcare community:

• Off-the-Shelf :

Our “cabinet” of HAVs of varying diameters and lengths is designed to be stored on-site at facilities such as hospitals, trauma centers and outpatient surgical centers.

• Immediately Available :

When needed, our HAVs are available for immediate use by opening and removing the HAV from its original flexible bioreactor bag.

Since our HAV does not need flushing, harvesting or thawing, as is common with other vascular substitute alternatives, we believe hospitals will be able to use our HAVs for vascular surgery more quickly with smaller surgical teams, reduced logistics and decreased overall cost.

• No Surgical Harvesting :

The use of our HAVs does not subject patients to the serious operation of harvesting an autologous vein, which can result in greater procedure and recovery time, potential scarring and disfigurement, increased costs, and numerous potential health complications.

• Non-Immunogenic and No Foreign Body Response :

Given their acellular nature, our HAVs have the potential to be universally implantable and durable across patients.

Because our HAVs are derived from human tissue (but cleansed of all cells and cellular components), we believe (and have observed in clinical trials to date) that they do not generate the foreign body response associated with the use of synthetic grafts, or the immune response associated with cryopreserved vessels.

• Low Infection Susceptibility :

In clinical trials to date, we have observed reduced rates of infection in our HAVs as compared to synthetic materials.

As a result, we believe our HAVs may be used in complicated and potentially contaminated wounds with fewer patient complications following the initial procedure.

• Uniform and Predictable Size, Structure and Quality :

Harvested veins vary in size, structure and quality by donor.

We manufacture our HAVs to precise specifications under controlled quality standards, which will allow surgeons the flexibility to quickly and easily select an HAV in the appropriate size and shape for each indication.

• Regenerative Potential :

Our HAVs repopulate with the patient’s own vascular cells, creating a living vascular tissue with the associated long-term benefits of self-healing and infection resistance.

If approved, we expect our HAVs would compete with the use of a patient’s own blood vessels, as well as a variety of marketed products, such as conventional synthetic grafts, xenografts, and allografts, as well as developing technologies.

We expect the key competitive factors affecting the commercial success of our HAVs to likely be efficacy, safety, convenience, pricing and reimbursement.

Other Commercial Entities

There are several conventional synthetic grafts made of ePTFE or Dacron presently on the market from companies such as Bard Peripheral Vascular, Inc., W.L.

Gore & Associates, Inc., Terumo Medical Systems, and Atrium (Maquet Getinge Group) that are used for both AV access for hemodialysis and vascular repair.

Xenograft and allograft products are also available, but not widely used.

Xenografts, such as Artegraft ® and Procol ® , are processed animal-derived vessels, while allografts are processed allogeneic cellular vessels, such as CryoVein ® and AngioGRAFT ® .

There are also a number of companies of which we are aware that have preclinical and early clinical-stage research programs underway to develop products that could potentially compete with our HAVs, including NovaHep AB, Xeltis AG, Hancock Jaffe, and Vascudyne Inc.

We may face competition from these and other emerging technologies such as bioabsorbable polymetric implants and electrospun or 3D printed tubular conduits.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are more effective, safer, have fewer or less severe side effects, are more convenient or are less expensive than the products that we develop.

Our competitors also may obtain FDA or other marketing approval for their products more rapidly than we may obtain the same approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

Government Regulation

The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements on the research, development, testing, manufacture, quality control, safety, effectiveness, packaging, labeling, storage, record keeping, marketing, advertising and promotion, import/export, and distribution of our vessels.

In the United States, the FDA regulates pharmaceutical drugs, medical devices and biologic products under the Federal Food, Drug, and Cosmetic Act (“FDCA”), the Public Health Service Act (“PHSA”), FDA implementing regulations, and other laws.

Our vessels are subject to regulation by the FDA as biologics.

Biologics require the submission of a BLA and approval by the FDA before being marketed in the United States.

None of our vessels have been approved by the FDA for marketing in the United States, and we currently have no BLAs pending.

If we fail to comply with applicable FDA or other requirements at any time during the product development process, clinical testing, and the approval process or after approval, we may become subject 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, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties or criminal prosecution.

Any FDA enforcement action could have a material adverse effect on us.

Marketing Approval — Biological Products in the United States

Before a biologic is approved in the United States, an applicant must submit a BLA that includes sufficient evidence to establish the safety, purity, and potency of the product candidate for its intended indications, including from the results of preclinical studies and clinical trials.

A BLA must also contain extensive information about manufacturing and product quality control testing, and the applicant must pass an FDA preapproval inspection of the manufacturing facility or facilities at which the biologic product is produced and distributed from to assess compliance with current good manufacturing practices, or cGMPs.

The steps for obtaining FDA approval of a BLA to market a biologic product in the United States generally include:

• Completion of extensive preclinical laboratory tests and preclinical animal studies performed in accordance with the FDA’s current good laboratory practice (“GLP”) regulations;

• Submission to the FDA of an Investigational New Drug application (“IND”), which must become effective before human clinical trials in the United States may begin;

• Approval of the protocol and related documentation by an Institutional Review Board (“IRB”) or ethics committee representing each clinical site before each clinical trial may be initiated;

• Performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as GCPs and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the product candidate for each proposed indication;

• Submission to the FDA of a BLA;

• Satisfactory completion of an FDA inspection of the manufacturing facility or facilities and distribution site at which the product is produced:

to assess compliance with cGMP regulations;

to assure that the facilities, production methods, testing and controls are adequate;

and, if applicable, to assure compliance with cGTP requirements for human cellular and tissue-derived products;

• Potential FDA audit of the nonclinical study and clinical trial sites that generated the data in support of the BLA;

• Review of the product candidate by an FDA advisory committee, if applicable;

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

• FDA review and approval, or licensure, of the BLA prior to any commercial marketing, sale or shipment of the product.

Biological Products Development Process

The testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for our vessels will be granted on a timely basis, if at all.

Once a product candidate is identified for development, that biologic candidate enters the preclinical testing stage.

Preclinical studies include laboratory evaluations of product chemistry, toxicity, formulation and stability, as well as animal studies to evaluate the product’s potential safety and activity.

The results of the preclinical studies, together with manufacturing information, analytical data, and at least one protocol for clinical study, are submitted to the FDA as part of an IND.

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 clinical trial, including concerns that human research subjects will be exposed to unreasonable health risks.

This is known as a “clinical hold.” In such a case, the IND sponsor must resolve all of the FDA’s concerns to the agency’s satisfaction before the clinical trial can begin.

Submission of an IND may result in the FDA not allowing the clinical trials to commence or not allowing the clinical trials to commence on the terms originally specified in the IND.

A separate submission to an existing IND must also be made for each successive clinical trial conducted during product development, and the FDA must grant permission, either explicitly or implicitly by not objecting, before each clinical trial can begin.

Even after a clinical trial has begun, the FDA can issue a clinical hold at any time if it concludes that certain conditions exist, such as patients may be exposed to an unreasonable and significant risk of illness or injury.

Clinical trials involve the use of the product candidate in human subjects under the supervision of qualified investigators.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be used.

Each protocol must be submitted to the FDA as part of the IND.

An independent IRB for each medical center proposing to conduct a clinical trial must also review and approve a plan for any clinical trial before it can begin at that center and the IRB must monitor the clinical trial until it is completed.

The IRB must review and approve, among other things, the study protocol and informed consent information to be provided to study subjects.

Some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee.

This group provides authorization as to whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the study.

Clinical testing also must satisfy extensive GCP requirements, including the requirements for informed consent.

Information about clinical trials must be submitted within specific timeframes to the National Institutes of Health (“NIH”) for public dissemination on its ClinicalTrials.gov website.

For purposes of BLA submission and approval, clinical trials are typically conducted in three sequential phases, which may overlap or be combined.

For Humacyte’s development of product candidates, Phase I and Phase II trials have heretofore been combined into a single trial design.

For the V005 trauma trial, we are in discussions with FDA about converting a Phase II/III study into a Phase III pivotal study.

The biological product is initially introduced into human subjects and tested for safety.

These initial trials to evaluate the potential toxicity and pharmacological activity of the investigational product (including pharmacokinetics, if applicable), and, if possible, gain early evidence on effectiveness.

The biological product is evaluated in a limited patient population to identify potential adverse events and safety risks, to evaluate preliminarily the efficacy of the product candidate for specific targeted indications in patients with the disease or condition under trial, and, when applicable, to evaluate dosage tolerance and appropriate dosage.

The biological product is administered to an expanded patient population, often large numbers of patients of several hundred to several thousand and generally at geographically dispersed clinical trial sites.

These trials are designed to generate enough data to statistically evaluate clinical effectiveness and safety as well as to establish the overall benefit-risk relationship of the investigational new biological product, and to provide an adequate basis for product approval.

FDA typically requires at least two Phase III trials to support approval, but in some cases may approve an application on the basis of one trial.

In some cases, the FDA may condition approval of a BLA on the sponsor’s agreement to conduct additional clinical trials to further assess the biologic’s safety and effectiveness after BLA approval.

Such post-approval clinical trials are typically referred to as Phase IV clinical trials.

During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical trial investigators.

Annual progress reports detailing the progress of the clinical trials must be submitted to the FDA.

Written IND safety reports must be promptly submitted to the FDA and the investigators detailing serious and unexpected adverse events, any findings from other studies that suggest a significant risk to human patients, tests in laboratory animals or in vitro testing that suggest a significant risk for human patients, or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting.

The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.

The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research patients are being exposed to an unacceptable health risk, including risks inferred from other trials on other products.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biological product has been associated with unexpected serious harm to patients.

Concurrent with clinical trials, companies usually complete additional animal trials and must also develop additional information about the characteristics of the biologic and finalize a process for manufacturing the biologic in commercial quantities in accordance with cGMP and, when applicable, GTP requirements.

The manufacturing process must be capable of consistently producing quality batches of the product candidate.

Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

BLA Review Process

The results of preclinical studies and of the clinical trials, together with other detailed information, including extensive manufacturing information, information on the composition of the biologic, and proposed labeling, are submitted to the FDA in the form of a BLA requesting approval to market the biologic in the United States for one or more specified indications.

The FDA reviews a BLA to determine, among other things, whether a biologic is safe and effective for its intended use.

The FDA has 60 days from its receipt of a BLA to determine whether the application will be accepted for filing based on the FDA’s threshold determination that the application is sufficiently complete to permit substantive review.

The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information.

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

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

After the BLA submission is accepted for filing, the FDA reviews the BLA to determine, among other things, whether the proposed product is safe and potent, or effective, for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMPs (and, where applicable, GTPs) to assure and preserve the product’s identity, safety, strength, quality, potency, and purity, and biological product standards.

The FDA may refer applications for novel biological products or biological

products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes outside clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and, if so, under what conditions.

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

Before approving an application, the FDA will, among other things, inspect the facility or the facilities at which the biologic product is manufactured and distributed, and will not approve the product unless cGMP compliance is satisfactory.

The FDA may also inspect the sites at which the clinical trials were conducted to assess their compliance, and may refuse to approve the biologic if compliance with GCP requirements is found to be unsatisfactory.

For a human cellular or tissue product the FDA also may refuse to approve the product if the manufacturer is not in compliance with GTP requirements, in addition to cGMPs.

The FDA also has authority to require a Risk Evaluation and Mitigation Strategy (“REMS”) from manufacturers to ensure that the benefits of a biological product outweigh its risks.

A sponsor may also voluntarily propose a REMS as part of the BLA submission.

The need for a REMS is determined as part of the review of the BLA.

Based on statutory standards, elements of a REMS may include “dear doctor letters,” a medication guide, more elaborate targeted educational programs, and in some cases restrictions on distribution and/or use.

These elements are negotiated as part of the BLA approval, and in some cases may delay the approval date.

Once adopted, REMS are subject to periodic assessment and modification.

The testing and approval processes require substantial time, effort and financial resources, and each may take several years to complete.

The FDA may not grant approval on a timely basis, or at all.

Even if we believe a clinical trial has demonstrated safety and efficacy of one of our vessels for the treatment of a disease, the results may not be satisfactory to the FDA.

Preclinical and clinical data may be interpreted by the FDA in different ways, which could delay, limit or prevent regulatory approval.

We may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing our vessels.

The FDA may limit the indications for use or place other conditions on any approvals that could restrict the commercial application of the products.

Biologics may be marketed only for the FDA approved indications and in accordance with the provisions of the approved labeling.

Further, if there are any modifications to the biologic, including changes in indications, labeling, or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new BLA or BLA supplement, which may require developing additional data or conducting additional preclinical studies and clinical trials.

As with new BLAs, the review process is often significantly extended by FDA requests for additional information or clarification.

The Biologics Price Competition and Innovation Act (“BPCIA”), amended the PHSA to authorize the FDA to approve similar versions of innovative biologics, commonly known as biosimilars.

A competitor seeking approval of a biosimilar must file an application to establish its product as highly similar to an approved innovator biologic, among other requirements.

The BPCIA, however, bars the FDA from approving biosimilar applications for 12 years after an innovator biological product receives initial marketing approval.

This bar does not apply to submission or approval of full BLAs.

Because FDA has determined that our HAVs are regulated as biologics and require a BLA for marketing, we believe that our lead product will be entitled to 12 years of exclusivity upon approval.

Nevertheless, the BPCIA is complex and is only beginning to be interpreted and implemented by the FDA.

As a result, its ultimate impact, implementation and meaning is subject to uncertainty.

Expedited Development and Review Programs

The FDA offers various programs, including Fast Track designation, Breakthrough Therapy Designation, accelerated approval, priority review and RMAT designation, that are intended to expedite the process for the development and FDA review of biological products that are intended for the treatment of serious or life-threatening diseases or conditions.

To be eligible for Fast Track designation, biological product candidates must be intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.

Fast Track designation applies to the combination of the product and the specific indication for which it is being studied.

The sponsor of a biological product candidate may request the FDA to designate the biologic as a Fast Track product at any time during the clinical development of the product.

The sponsor of a Fast Track product has opportunities for more frequent interactions with the applicable FDA review team during product development and, once a BLA is submitted, the product candidate may be eligible for priority review.

A Fast Track product may also be eligible for rolling review, where the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and

determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.

A biological product candidate may be eligible for Breakthrough Therapy Designation if it is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

Breakthrough Therapy Designation provides all the features of Fast Track designation in addition to intensive guidance on an efficient development program beginning as early as Phase I, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where appropriate.

Any marketing application for a biological product submitted to the FDA for approval, including a product candidate with a Fast Track designation and/or Breakthrough Therapy Designation, may be eligible for other types of FDA programs intended to expedite the FDA review and approval process, such as priority review and accelerated approval.

Any product candidate is eligible for priority review if it is designed to treat a serious or life-threatening disease or condition, and if approved, would provide a significant improvement in safety or effectiveness compared to available alternatives for such disease or condition.

The FDA will attempt to direct additional resources to the evaluation of an application for a biological product candidate designated for priority review in an effort to facilitate the review.

Under priority review, the FDA’s goal is to review an application within six months of the 60-day filing date, compared to ten months for a standard review.

Additionally, FDA may grant accelerated approval to a product candidate intended to treat a serious or life-threatening disease or condition upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, 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.

As a condition of approval, the FDA may require that a sponsor of a biological product receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit.

Products receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails to conduct the required post-marketing studies or if such studies fail to verify the predicted clinical benefit.

In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

In 2017, the FDA established a new RMAT designation as part of its implementation of the 21st Century Cures Act.

The RMAT designation program is intended to fulfill the 21st Century Cures Act requirement that the FDA facilitate an efficient development program for, and expedite review of, any biological product that meets the following criteria:

(i) the biological product qualifies as an RMAT, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, with limited exceptions;

(ii) the biological product is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition;

and preliminary clinical evidence indicates that the biological product has the potential to address unmet medical needs for such a disease or condition.

RMAT designation provides all the benefits of Breakthrough Therapy Designation, including more frequent meetings with the FDA to discuss the development plan for the product candidate and eligibility for rolling review and priority review.

Product candidates granted RMAT designation may also be eligible for accelerated approval on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of clinical trial sites, including through expansion of trials to additional sites.

Fast Track designation, Breakthrough Therapy Designation, priority review, accelerated approval, and RMAT designation do not change the standards for approval but may expedite the development or approval process.

Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Additionally, on December 12, 2017, Public Law No.

115-92 amended the FDCA to, among other things, allow the DoD to request, and FDA to provide assistance to expedite development and the FDA’s review of products to diagnose, prevent, treat or mitigate a specific and life-threatening risk to the U.S.

Similar to the designations described above that FDA may grant, a priority designation by the DoD does not change the standards for approval but may expedite the development or approval process.

Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a biological product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a biological product available in the United States for this type of disease or condition will be recovered from sales of the product.

Orphan product designation must be requested before submitting a BLA.

After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

Orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biological product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity, or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated.

Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.

A designated orphan drug many not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation.

In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if a second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Regulatory Requirements

For biologics that are human cells, tissues, and cellular and tissue-based products (“HTC/Ps”), manufacturers must also comply with the FDA’s HCT/P regulations at 21 C.F.R.

These regulations impose a variety of specialized requirements as follows:

HCT/P registration and listing.

Every establishment that manufactures an HCT/P must register with the FDA and provide a list of every HCT/P that the establishment manufactures.

The definition of manufacture is broad and includes any and all steps in the recovery, processing, storage, labeling, packaging or distribution of any human cell or tissue and the screening or testing of the cell or tissue donor.

Donor eligibility.

HCT/P manufacturers must maintain procedures for testing, screening and determining the eligibility of donors of cells and tissues used in HCT/Ps.

An HCT/P may not be transferred or implanted into an individual until the donor has been determined to be eligible under these procedures.

These procedures must involve, among other things, testing donors for certain communicable diseases and the use of quarantines for HCT/Ps that have not yet been shown to meet the eligibility requirements.

Manufacturers must keep detailed records regarding donor eligibility determinations.

Current Good Tissue Practices.

HCT/Ps must be recovered, processed, stored, labeled, packaged and distributed in a manner that is consistent with the FDA’s cGTP regulations.

Cells and tissues must also be screened and tested according to these regulations.

The goal of cGTPs is to prevent the introduction, transmission or spread of communicable diseases.

The FDA’s cGTPs regulations require companies to establish a comprehensive quality program and to comply with rules related to personnel, facilities and equipment used to manufacture HCT/Ps, as well as rules on how these HCT/Ps are processed, labeled and stored.

Companies must also keep detailed manufacturing records and product complaint files.

Adverse Reaction Reports.

Manufacturers of nonreproductive HCT/Ps must investigate and report to the FDA certain adverse reactions.

Establishments that manufacture HCT/Ps must allow the FDA to inspect the establishment and company records.

Post-Approval Requirements

Any biologics manufactured or distributed by us or our collaborators pursuant to FDA approvals would be subject to continuing post-approval regulation by the FDA, including recordkeeping requirements and reporting of adverse experiences associated with the product, as well as any post-marketing surveillance requested by the FDA as a condition to BLA approval.

Manufacturers and 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 and certain state agencies for compliance with ongoing regulatory requirements, including cGMPs, which impose certain procedural and documentation requirements upon us and our third-party manufacturers.

Failure to comply with the statutory and regulatory requirements can subject a manufacturer to possible legal or regulatory action, such as warning letters, suspension of manufacturing, seizure of product, injunctive action or possible civil penalties.

We cannot be certain that we or our present or future third-party manufacturers or suppliers will be able to comply with the cGMP regulations and other ongoing FDA regulatory requirements.

If we or our present or future third-party manufacturers or suppliers are not able to comply with these requirements, the FDA may halt our clinical trials, require us to recall our product from distribution or withdraw approval of the BLA for that product.

The FDA closely regulates the post-approval marketing and promotion of biologics to healthcare professionals, including standards and regulations for direct-to-consumer advertising, false or misleading claims, off-label promotion, industry-sponsored scientific and educational activities, and promotional activities involving the Internet.

Failure to comply with these requirements can result in adverse publicity, warning letters, corrective advertising, and potential civil and criminal penalties.

Physicians may prescribe legally available biologics for uses that are not described in the product’s labelling and that differ from those tested by us and approved by the FDA.

Such off-label uses are common across medical specialties.

Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.

The FDA does not regulate the behavior of physicians in their choice of treatments.

The FDA does, however, impose stringent restrictions on manufacturers’ communications regarding off-label use.

Healthcare Reform

Political, economic and regulatory influences are subjecting the healthcare industry in the United States to fundamental changes.

There have been, and we expect there will continue to be, legislative and regulatory proposals to significantly change the healthcare system.

For example, the Patient Protection and Affordable Care Act (the “ACA”) was enacted to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.

In December 2017, portions of the ACA dealing with the individual mandate insurance requirement were effectively repealed by the Tax Cuts and Jobs Act of 2017.

Third-Party Payor Coverage and Reimbursement

Although none of our vessels have been commercialized for any indication, if they are approved for marketing, commercial success of our vessels will depend, in part, upon the availability of coverage and reimbursement from third-party payors at the federal, state and private levels.

Government payor programs, including Medicare and Medicaid, private health care insurance companies and managed-care plans have attempted to control costs by limiting coverage and the amount of reimbursement for particular procedures or treatments.

Congress and state legislatures from time to time propose and adopt initiatives aimed at cost-containment.

Ongoing federal and state government initiatives directed at lowering the total cost of health care will likely continue to focus on health care reform and on the reform of the Medicare and Medicaid payment systems.

Examples of how limits on coverage and reimbursement in the United States may cause reduced payments for products in the future include:

changing Medicare reimbursement methodologies;

fluctuating decisions on which drugs to include in formularies;

allowing the federal government to negotiate drug prices for federal healthcare programs;

revising drug rebate calculations under the Medicaid program;

and reforming drug importation laws.

Some third-party payors also require pre-approval of coverage for new or innovative devices or therapies before they will reimburse health care providers who use such therapies.

While we cannot predict whether any proposed cost-containment measures will be adopted or otherwise implemented in the future, the announcement or adoption of these proposals could have a material adverse effect on our ability to obtain adequate prices for our vessels and operate profitably.

Significant cost containment pressure and downward pricing pressures exist in the U.S.

and around the world, which may negatively affect reimbursement at any time.

Other Healthcare Laws and Regulations

We are also subject to healthcare regulation and enforcement by the federal government and the states and foreign governments in which we conduct our business.

The laws that may affect our ability to operate include but are not limited to:

• the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in exchange for or to induce either the referral of an individual for, or the purchase, order or recommendation of, any good or service for which payment may be made under federal healthcare programs such as the Medicare and Medicaid programs;

• federal false claims laws which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent;

• federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

• the federal Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act (collectively, “HIPAA”), which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information;

• the federal Physician Payments Sunshine Act, which requires drug and device companies to annually report to CMS all payments and transfers of value provided to physicians and teaching hospitals for posting on a public website;

• state law equivalents of many of the above federal laws, including anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payor, including commercial insurers.

If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, the curtailment or restructuring of our operations, the exclusion from participation in federal and state healthcare programs and imprisonment, any of which could adversely affect our ability to operate our business and impact our financial results.

International Regulation

In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our future products.

Whether or not we obtain FDA approval for a product, we must obtain approval of a product by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries.

The approval process varies from country to country, and the time may be longer or shorter than that required for FDA approval.

The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country.

EU Requirements Applicable to Medicinal Products

In the EU, medicinal products are subject to extensive pre-and post-market regulation by regulatory authorities at both the EU and national levels.

Clinical Trials

Clinical trials of medicinal products in the EU must be conducted in accordance with EU (previously, Directive 2001/20/EC applied;

as of January 31, 2022, Regulation EU No 536/2014 applies) and national regulations and the International Conference on Harmonization (“ICH”) guidelines on GCP.

Prior to commencing a clinical trial, the sponsor must obtain a clinical trial authorization from the competent authority, and a positive opinion from an independent ethics committee of the relevant EU Member State in which the clinical trial will be carried out.

Any substantial changes to the trial protocol or other information submitted with the clinical trial applications must be notified to or approved by the relevant competent authorities and ethics committees.

The sponsor of a clinical trial must register the clinical trial in advance, and certain information related to the clinical trial will be made public as part of the registration.

The results of the clinical trial must be submitted to the competent authorities and, with the exception of non-pediatric Phase I trials, will be made public at the latest within 12 months after the end of the trial.

During the development of a medicinal product, the European Medicines Agency (“EMA”) and national medicines regulators within the EU provide the opportunity for dialogue and guidance on the development program.

At the EMA level, this is usually done in the form of scientific advice, which is given by the Scientific Advice Working Party of the Committee for Medicinal Products for Human Use (“CHMP”).

Advice is not legally binding with regard to any future marketing authorization application of the product concerned.

To date, we have not initiated any scientific advice procedures with the EMA, but we have obtained confirmation from the EMA that our HAVs would be eligible for the EMA’s scientific advice procedures.

Marketing Authorizations

After completion of the required clinical testing, we must obtain a marketing authorization before we may place a medicinal product on the market in the EU.

There are various application procedures available, depending on the type of product involved.

All application procedures require an application in the common technical document format, which includes the submission of detailed information about the manufacturing and quality of the product, and non-clinical and clinical trial information.

There is an increasing trend in the EU towards greater transparency and, while the manufacturing or quality information is currently generally protected as confidential information, the EMA and national regulatory authorities are now liable to disclose much of the non-clinical and clinical information in marketing authorization dossiers, including the full clinical study reports, in response to freedom of information requests after the marketing authorization has been granted.

The centralized procedure gives rise to marketing authorizations that are valid throughout the EU.

Applicants file marketing authorization applications with the EMA, where they are reviewed by a relevant scientific committee, in most cases the CHMP (although other specialist committees may also be involved;

for example, the Committee for Advanced Therapies will also be involved in the review of advanced therapy medicinal products (“ATMP”), and HAVs could potentially be classified as an ATMP).

The EMA forwards CHMP opinions to the European Commission, which uses them as the basis for deciding whether to grant a marketing authorization.

The centralized procedure is compulsory for medicinal products that (1) are derived from biotechnology processes, (2) contain a new active substance (not yet approved on 20 November 2005) indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders, viral diseases or autoimmune diseases and other immune dysfunctions, (3) are orphan medicinal products or (4) are advanced therapy medicinal products.

For medicines that do not fall within these categories, an applicant may voluntarily submit an application for a centralized marketing authorization to the EMA, as long as the CHMP agrees that (i) the medicine concerned contains a new active substance (not yet approved on November 20, 2005), (ii) the medicine is a significant therapeutic, scientific, or technical innovation, or if its authorization under the centralized procedure would be in the interest of public health.

For those medicinal products for which the centralized procedure is not available, the applicant must submit marketing authorization applications to the national medicines regulators through one of three procedures:

(1) a national procedure, which results in a marketing authorization in a single EU member state;

(2) the decentralized procedure, in which applications are submitted simultaneously in two or more EU member states;

and (3) the mutual recognition procedure, in which the EU member states are required to grant an authorization recognizing an existing authorization in another EU member state, unless they identify a serious risk to public health.

Data Exclusivity

Marketing authorization applications for generic medicinal products do not need to include the results of preclinical and clinical trials, but instead can refer to the data included in the marketing authorization of a reference product for which regulatory data exclusivity has expired.

If a marketing authorization is granted for a medicinal product containing a new active substance or to a different marketing authorization holder that has carried out a complete set of pre-clinical tests and clinical trials, that product benefits from eight years of data exclusivity, during which generic marketing authorization applications referring to the data of that product may not be accepted by the regulatory authorities, and a further two years of market exclusivity, during which such generic products may not be placed on the market.

The two-year period may be extended to three years if during the first eight years a new therapeutic indication with significant clinical benefit over existing therapies is approved.

There is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product, for example, because of differences in raw materials or manufacturing processes.

For such products, while a full set of pre-clinical tests and trials are not necessary, the results of appropriate preclinical or clinical trials must be provided, and guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product.

Pediatric Development

In the EU, companies developing a new medicinal product must agree to a Pediatric Investigation Plan (“PIP”) with the EMA and must conduct pediatric clinical trials in accordance with that PIP.

The marketing authorization application for the product must ordinarily include the results of pediatric clinical trials conducted in accordance with the PIP.

It is possible to obtain a deferral, in which case the pediatric clinical trials must be completed at a later date, or a complete waiver from the obligation to conduct pediatric clinical trials (e.g., because the relevant disease or condition occurs only in adults).

Post-Approval Controls

The holder of a marketing authorization is subject to various post-approval controls, such as obligations to maintain a pharmacovigilance system and report adverse reactions, and requirements relating to promotional activities, including a prohibition on the promotion of prescription medicines to the general public.

Manufacturers/importers and distributors of medicinal products must obtain authorizations from the competent national authorities and are subject to periodic inspections for compliance with cGMPs and current good distribution practices (“cGDPs”), respectively.

The regulatory authorities may also impose specific obligations as a condition of the marketing authorization, such as additional safety monitoring or the conduct of additional clinical trials or post-authorization safety studies.

EU Requirements Applicable to Medical Devices

Under the previous medical devices directive, Directive 93/42/EEC, our HAVs were not classified as medical devices in the EU because, with limited exceptions, products incorporating or derived from tissues or cells of human origin are expressly excluded from the scope of the EU medical devices rules under Directive 93/42.

However, as of May 26, 2021, Regulation (EU) 2017/745 applies, and this will bring us within the scope of the EU medical device rules products containing or derived from tissues or cells of human origin that are non-viable or are rendered non-viable.

Medical devices are generally governed by Regulation (EU) 2017/745 on Medical Devices that directly applies in all EU Member States and harmonizes the conditions for placing medical devices on the EU market.

This Regulation, however, does not regulate certain important marketing aspects, such as pricing and reimbursement, which remain governed by national law.

Additionally, certain areas, such as advertising, may be governed by additional national requirements.

A medical device may be placed on the market within the EU if it conforms to certain “general product safety requirements” or “GSPRs.” These are general in nature and broad in scope.

A fundamental GSPR, for example, is that a device must be designed and manufactured in such a way that it will not compromise the clinical condition or safety of patients, or the safety and health of users or other persons.

The manufacturer is obliged to demonstrate that the device conforms to the relevant GSPRs through a conformity assessment procedure.

Once the appropriate conformity assessment procedure for a medical device has been completed, the manufacturer must draw up a written declaration of conformity and affix the CE mark to the device.

The device can then be marketed throughout the EU.

The nature of the conformity assessment depends upon the classification of the device.

The classification rules are mainly based on three criteria:

the length of time the device is in contact with the body, the degree of invasiveness, and the extent to which the device affects the anatomy.

As a general rule, Class I (low risk) devices are those that do not enter or interact with the body;

Class IIa and IIb (medium risk) devices are invasive or implantable or interact with the body;

and Class III (high risk) devices are those that affect the vital organs.

Conformity assessment procedures for all but the lowest risk classification of device involve a notified body, which are non-governmental, private entities licensed to provide independent certification of certain classes of medical device.

EU regulatory bodies are not involved in the premarket approval of medical devices, with only very limited exceptions (such as medical devices that incorporate a medicinal product as an ancillary substance, in which case these regulatory bodies

review the medicinal product).

The onus of ensuring a device is safe enough to be placed on the market is ultimately the responsibility of the manufacturer and the notified body.

As part of the conformity assessment procedure, the manufacture will need to conduct a clinical evaluation of the device.

This clinical evaluation may consist of an analysis of the scientific literature relating to similar devices, new clinical investigations of the device, or a combination of the two.

For Class III and implantable devices, the conduct of clinical investigations is mandatory (with limited exceptions).

If a manufacturer wishes to conduct a clinical investigation in the EU, the manufacturer must notify the competent national regulatory authorities in advance and obtain ethics committee approval of the study.

EU Requirements Applicable to Human Cells and Tissues

EU rules, notably Directive 2004/23/EC and other implementing directives, govern the donation, procurement, testing and storage of human cells and tissues intended for human application, whether or not they are medicinal products.

These rules also cover the donation, testing, processing, preservation, storage and distribution of human cell and tissues that are not medicinal products.

Establishments that conduct such activities must be licensed and are subject to inspection by regulatory authorities.

Such establishments must implement appropriate quality systems and maintain appropriate records to ensure that cells and tissues can be traced from the donor to the recipient and vice versa.

There are also requirements to report SAEs and reactions linked to the quality and safety of cells and tissues.

More detailed rules may exist at the national level.

In addition to regulations in Europe and the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial distribution of our future products.

Our corporate headquarters, manufacturing, and research and development facilities are located in Durham, North Carolina where we lease approximately 83,000 square feet of space.

This space includes approximately 55,000 square feet for production and distribution operations including manufacturing, bioprocessing, quality control, mechanical space and inventory.

The remainder of the facility consists of offices, laboratories, and common spaces.

Employees and Human Capital Management

As of December 31, 2021, we had 146 employees, including 145 full-time employees.

None of our employees are represented by a collective bargaining agreement, and we have never experienced any work stoppage.

We believe we have good relations with our employees.

Financing Arrangements

In March 2021, Legacy Humacyte entered into a Loan Agreement with Silicon Valley Bank and SVB Innovation Credit Fund VIII, L.P., which provides a term loan facility of up to $50.0 million with a maturity date of March 1, 2025.

We became a co-borrower under the Loan Agreement in connection with the Merger.

The obligations of Humacyte and Legacy Humacyte under the Loan Agreement are secured by substantially all of their assets, except for their intellectual property.

In connection with the Loan Agreement, the lenders were each granted a warrant to purchase Legacy Humacyte common stock, with an exercise price of $2.699 per share, subject to customary adjustments.

In connection with the closing of the Merger, these warrants were exchanged for warrants to purchase 287,704 shares of our common stock at an exercise price of $10.28 per share.

On October 13, 2021, we borrowed an additional $10.0 million under the Loan Agreement, and in connection with that borrowing, issued Silicon Valley Bank and SVB Innovation Credit Fund VIII, L.P.

warrants to purchase an aggregate of 123,302 shares of our common stock at an exercise price of $10.28 per share.

The Loan Agreement contains certain customary covenants, including, but not limited to, those relating to additional indebtedness, liens, asset divestitures, and affiliate transactions.

We may use the proceeds of borrowings under the Loan Agreement as working capital and to fund our general business requirements.

As of February 28, 2022, we had borrowed $30.0 million of principal under the Loan Agreement.

Additional Information

We were incorporated in Delaware on July 1, 2020, under the name Alpha Healthcare Acquisition Corp.

(“AHAC”), in order to effectuate a merger, capital stock exchange, asset acquisition, stock purchase, reorganization or similar business combination with one or more businesses or entities.

AHAC completed its initial public offering on September 22, 2020.

On August 26, 2021, AHAC and Legacy Humacyte consummated the transactions contemplated by the Merger Agreement.

In connection with the closing of the Merger, we changed our name to Humacyte, Inc.

Our principal executive office is located at 2525 East North Carolina Highway 54, Durham, North Carolina 27713, and our telephone number is (919) 313-9633.

Our website address is www.humacyte.com and our investor relations website is located at https://investors.humacyte.com.

The information posted on our website is not incorporated into this Annual Report on Form 10-K.

Securities and Exchange Commission (“SEC”) maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC at http://www.sec.gov.

Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Securities Exchange Act of 1934, as amended, (the “Exchange Act”) are also available free of charge on our investor relations website as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

We provide notifications of news or announcements regarding our financial performance, including SEC filings, investor events, and press releases, as part of our investor relations website.

The contents of these websites are not intended to be incorporated by reference into this report or in any other report or document we file.

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