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Item 1A. Risk Factors

2025-03-31 compared with 2024-03-28 · 258 added, 217 removed, 713 unchanged (40% of the section changed)

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We will need to raise additional capital to finance our operations, which we may not be able to do on acceptable terms or at all.

• Our near-term prospects are dependent on the success of Symvess, our sole FDA-approved product, and if we are unable to successfully commercialize it in the vascular trauma indication and obtain regulatory approval for Symvess in additional indications, our business, operating results and financial condition will be materially harmed.

• Symvess and our product candidates, if approved, may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

• We face and will continue to face substantial competition, which may result in others discovering, developing or commercializing competing products before or more successfully than we do, which may adversely affect our ability to successfully market or commercialize Symvess or our product candidates.

• If our clinical trials fail to demonstrate safety and efficacy to the satisfaction of the FDA or similar regulatory authorities outside the United States or do not otherwise produce favorable results, we may incur significant additional costs or experience significant delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates.

• Our near-term prospects are dependent on the success of our 6 millimeter HAV, and if we are unable to successfully develop and commercialize it, our business, operating results and financial condition will be materially harmed.

• We may experience delays or difficulties in the enrollment of patients in our clinical trials, which may delay or prevent additional clinical trials and our receipt of necessary marketing approvals.

• Lack of experience by investigators and surgeons with our HAVs can lead to incorrect implantation or follow-up procedures which could harm the results of our clinical trials and market acceptance of our HAVs, if approved.

• Lack of experience by investigators and surgeons with our ATEVs can lead to incorrect implantation or follow-up procedures which could harm the results of our clinical trials and market acceptance of Symvess and our product candidates, if approved.

• We may not be successful in our efforts to use our proprietary scientific technology platform to build a pipeline of additional product candidates.

• Even if our HAVs receive marketing approval in the future for one or more of our product candidates, they may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

• 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.

• The sizes of the market opportunities for Symvess and 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.

• Our distribution agreement with Fresenius Medical Care imposes obligations on us that may restrict our ability to operate our business in ways we believe to be in our long-term best interest.

• If we receive approval for a product candidate that is not subject to our distribution agreement with Fresenius Medical Care, and we are unable to establish our own marketing, sales and distribution capabilities or are unable to enter into agreements with third parties do so, we may not be able to generate product revenue and will have to alter our development and commercialization plans.

• The manufacture of our product candidates is complex, we have not manufactured commercial product, and we may encounter difficulties in production.

If we or any third-party manufacturer encounter such difficulties, our ability to supply our product candidates for clinical trials or, if approved, for commercial sale could be delayed or halted entirely.

• The terms of the Purchase Agreement may limit our ability to incur future debt.

• If we receive approval for a product candidate that is not subject to our distribution agreement with Fresenius Medical Care, and we are unable to establish our own marketing, sales and distribution capabilities or are unable to enter into agreements with third parties to do so, we may not be able to generate product revenue and will have to alter our development and commercialization plans.

• The manufacture of Symvess and our product candidates is complex, we have limited experience manufacturing commercial product, and we have in the past and may in the future encounter difficulties in production.

If we or any third-party manufacturer encounter such difficulties, our ability to supply Symvess for commercial sale or Symvess and our product candidates for clinical trials could be delayed or halted entirely.

• The terms of the Purchase Agreement (defined below) may limit our ability to incur future debt.

• We rely on third parties to conduct and support our clinical trials, and those third parties may not perform satisfactorily, including by failing to adhere to regulatory requirements or our stated protocols or to meet deadlines for the completion of such trials.

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Disruption of this arrangement could materially adversely affect our business, prospects, operating results and financial condition.

• Our ability to successfully commercialize our products may be impaired if we are unable to obtain and maintain effective intellectual property rights for our proprietary scientific technology platform and product candidates.

• Our ability to successfully commercialize Symvess and our product candidates may be impaired if we are unable to obtain and maintain effective intellectual property rights for our proprietary scientific technology platform and product candidates.

• We may be required to take write-downs or write-offs, restructuring and impairment or other charges that could have a significant negative effect on our financial condition, results of operations and stock price, which could cause you to lose some or all of your investment.

Risks Related to the Development and Commercialization of Our Product Candidates

Risks Related to the Development of Symvess and Commercialization of Our Product Candidates

Our near-term prospects are dependent on the success of Symvess, our sole FDA-approved product, and if we are unable to successfully commercialize it in the vascular trauma indication and obtain regulatory approval for Symvess in additional indications, our business, operating results and financial condition will be materially harmed.

Our business currently depends heavily on our ability to successfully commercialize Symvess in the United States and in other jurisdictions where we may obtain marketing approval.

Symvess currently is our only product approved for sale in the US and, while we are developing a number of product candidates, we have invested and continue to invest a substantial portion of our efforts and financial resources in the development of Symvess.

None of our remaining product geometries and modifications have advanced beyond preclinical development.

As a result, in the near term we are dependent on the success of Symvess, and if we are unable to successfully commercialize it in the vascular trauma indication and obtain regulatory approval for Symvess in additional indications, our business, along with our operating results and financial condition, will be materially harmed.

We may never be able to successfully commercialize Symvess or our product candidates or meet our expectations with respect to revenues for a number of reasons, including:

• a lack of acceptance of Symvess by physicians, patients, third-party payors and other members of the medical community;

• our limited experience in marketing, selling and distributing Symvess or any other product;

• our limited experience in the commercial manufacturing of Symvess or any other product;

• reimbursement and coverage policies of government and private payors such as Medicare, Medicaid, group purchasing organizations, insurance companies, health maintenance organizations and other plan administrators;

• our ability to expand the current FDA-approved indications for Symvess into treatment of pediatric patients, treatment of a broader set of traumas, or indications outside of trauma;

• emergence of new AEs associated with Symvess once the product is in commercial use or data suggesting that known AEs are more frequent or severe than originally thought;

• changed or increased regulatory restrictions in the United States, EU and other foreign territories;

• a lack of adequate financial or other resources to commercialize Symvess successfully.

For example, during its review of the Symvess BLA, the FDA identified concerns relating to mid-graft rupture or anastomotic failure of Symvess post-implantation.

As a result, the FDA approved package insert for Symvess contains a boxed warning relating to mid-graft rupture or anastomotic failure, and as a condition of Symvess approval we are obliged to conduct a post-approval long-term observational study to further characterize these and other risks.

If our post-approval study demonstrates that these or other risks associated with Symvess are more severe and/or more prevalent than currently understood, this may have adverse impacts on our business, including lack of market acceptance of our product, imposition of further warnings or limitations on distribution and/or use of Symvess, or revocation of our marketing authorization.

There is no guarantee that the infrastructure, systems, processes, policies, relationships, and materials we have built for the launch and commercialization of our approved product in the United States will be sufficient for us to achieve success at the levels we expect.

Even our ability to generate product revenue and become profitable from Symvess depends on our assumptions regarding the relevant market opportunity and the degree of market acceptance for Symvess, and if approved, our other products, for which our estimates may prove inaccurate, and market acceptance in any approved indication, which may never occur.

Symvess and our product candidates, if approved, may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

The commercial success of Symvess and our product candidates will depend, in part, on the acceptance of physicians, patients and health care payors, as medically necessary, cost-effective and safe.

Symvess and any other product that we commercialize may not gain acceptance by physicians, patients, health care payors and others in the medical community due to ethical, social, medical, cost and legal concerns.

If these products do not achieve an adequate level of acceptance, we may not generate significant product revenue and may not become profitable.

The degree of market acceptance of Symvess or any of our product candidates that receives marketing approval will depend on a number of factors, including:

• the efficacy and potential advantages of Symvess or our product candidates compared with alternative products or methods, including convenience and ease of administration;

• the prices we charge for Symvess or our other products, if approved;

• the availability of third-party coverage and adequate reimbursement;

• the willingness of the target patient population to try new products and methods and of physicians to use these products and methods;

• the strength of marketing and distribution support;

• the availability of the product and our ability to meet market demand;

• the prevalence and severity of any side effects, or the emergence of new, previously unknown side effects;

• any restrictions on the use of Symvess and our other products, if approved.

If our clinical trials are delayed, do not produce favorable results, or otherwise fail to demonstrate safety and efficacy to the satisfaction of the FDA or similar regulatory authorities outside the United States, we may incur significant additional costs or experience significant delays in completing, or ultimately be unable to complete, the development, approval, and commercialization of our product candidates.

If we experience significant delays or significant additional costs, our business will be materially harmed.

Before obtaining marketing approval for any of our product candidates, we must conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans.

Before obtaining marketing approval for any of our product candidates, and before gaining approval for additional indications for our approved Symvess product, we must conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans.

Clinical testing is expensive and time-consuming, and its outcomes are uncertain.

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The scientific discoveries that form the basis for our efforts to develop our product candidates are relatively new, and the scientific evidence to support the feasibility of developing product candidates based on these discoveries is both preliminary and limited.

At this time, no products based on HAVs have been approved in the United States, Europe or in any other jurisdiction.

At this time, Symvess has been approved in the United States in an initial indication, and none of our product candidates have been approved in the United States, Europe or in any other jurisdiction.

The clinical trial requirements of the FDA and other regulatory agencies and the criteria these regulators use to determine the safety and efficacy of a product candidate vary substantially according to the type, complexity, novelty and intended use and market of the potential product.

In addition, because of the nature of the HAVs, many of our clinical trials are “open label,” meaning that both the patient and the investigator know whether the patient is receiving the investigational product candidate.

In addition, because of the nature of the ATEVs, many of our clinical trials are “open label,” meaning that both the patient and the investigator know whether the patient is receiving the investigational product candidate.

These studies often require the use of historical control arms consisting of patients previously treated with alternative therapies in the normal course of medical care.

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If our studies are not successful, we be delayed in obtaining marketing approval or may not receive marketing approval at all.

For example, our V006 trial did not meet its primary endpoint, which has delayed development of the HAV for the hemodialysis access indication.

For example, our V006 trial did not meet its primary endpoint, which has delayed development of the ATEV for the hemodialysis access indication.

If we fail to achieve the primary endpoint of our other ongoing or future clinical trials, or if safety issues arise, or the results from our clinical trials are otherwise inadequate to support regulatory approval of our product candidates, we may incur significant additional costs or experience significant delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates.

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In such a circumstance, the FDA may require that we design and conduct new, additional clinical trials to demonstrate safety and effectiveness, or may determine not to approve our products at all.

Additionally, even if we receive FDA approval for our HAVs, we may face a number of difficulties if the results of our clinical trials are unfavorable, inconclusive, or only modestly favorable or if there are safety concerns, such as adverse events (“AEs”) or SAEs, which could include clotting, mechanical failure, immunological rejection or infection, that could outweigh potential benefits associated with such product candidates.

Additionally, even though we received FDA approval for Symvess in trauma, we may face a number of difficulties if the results of our clinical trials for additional Symvess indications or for our product candidates are unfavorable, inconclusive, or only modestly favorable or if there are safety concerns, such as AEs or SAEs, which could include clotting, mechanical failure, immunological rejection or infection, that could outweigh potential benefits associated with such product candidates.

This could result in:

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Any of these events could cause us to incur significant additional costs, significant delays and prevent us from achieving or maintaining market acceptance of or commercializing one or more of our product candidates.

Our progress in early stage clinical trials may not be indicative of long-term efficacy in late stage clinical trials, and our progress in trials for one product candidate may not be indicative of progress in trials for another product candidate.

Our progress in early stage clinical trials may not guarantee success in late stage clinical trials, and our progress in trials for one product candidate or the FDA’s approval of Symvess may not be indicative of progress in trials for another product candidate.

The product candidates in our pipeline are at various stages of development.

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A number of companies in the biotechnology industry have suffered significant setbacks in late-stage clinical trials even after achieving promising results in earlier stage clinical trials, and we may experience similar setbacks.

Favorable results in clinical trials for one of our product candidates also do not necessarily indicate that we will obtain positive results in clinical trials related to other product candidates.

The novelty of our proprietary scientific technology platform adds another layer of risk that early-stage clinical trials may not be indicative of long-term efficacy in our late-stage clinical trials.

Favorable results in clinical trials for, or the FDA’s approval of, one of our product candidates also do not necessarily indicate that we will obtain positive results in clinical trials related to product candidates.

The novelty of our proprietary scientific technology platform adds another layer of risk that early-stage clinical trials may not guarantee success in our late-stage clinical trials.

If we are unable to demonstrate favorable results in future clinical trials for our various product candidates, we expect that our business, prospects, operating results and financial condition will be materially adversely affected.

Additionally, several of our past, planned and ongoing clinical trials utilize an “open-label” trial design.

An “open-label” clinical trial is one where both the patient and investigator know whether the patient is receiving the investigational product candidate.

Some open-label clinical trials test only the investigational product candidate without a comparator.

Open-label clinical trials are subject to various limitations that may exaggerate any therapeutic effect as patients in open-label clinical trials are aware when they are receiving treatment.

Open-label clinical trials may be subject to a “patient bias” where patients perceive their symptoms to have improved merely due to their awareness of receiving an experimental treatment.

In addition, open-label clinical trials may be subject to an “investigator bias” where those assessing and reviewing the physiological outcomes of the clinical trials are aware of which patients have received treatment and may interpret the information of the treated group more favorably given this knowledge.

The results from an open-label trial may not be predictive of future clinical trial results with any of our product candidates when studied in an environment with an active control.

Interim, “topline,” and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, we may publicly disclose preliminary or topline data from our clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial.

From time to time, we may publicly disclose preliminary or topline data from our clinical trials, which is based on a preliminary analysis of then-available data.

However, the final results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial.

We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, although we may not have received or had the opportunity to fully and carefully evaluate all data at the time such preliminary or topline results are released.

As a result, the topline or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.

As a result, the topline or preliminary results that we report may differ from final results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated.

Topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published.

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In addition, the information we choose to publicly disclose regarding a particular clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure.

If SAEs occur at an unacceptable rate or other unacceptable side effects are identified in our HAVs we may need to delay, abandon or limit development and marketing of our product candidates.

Our HAVs may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude us from obtaining marketing approval.

If our HAVs are associated with undesirable side effects in clinical trials or have negative characteristics that are unexpected, we may need to perform additional clinical trials, abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective.

Even if one of our product candidates is approved, the FDA and other regulatory authorities may limit the scope of that approval, require us to include detailed warnings and/or contraindications in product labeling, and/or implement a REMS, which may include restrictions on distribution or use of the product.

If SAEs occur at an unacceptable rate or other unacceptable side effects are identified in our ATEVs we may need to delay, abandon or limit development and marketing of our product candidates.

Our ATEVs may prove to have undesirable or unintended side effects, toxicities or other characteristics.

If our ATEVs are associated with undesirable side effects in clinical trials or in commercial marketing, or have negative characteristics that are unexpected, we may need to perform additional clinical trials, abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective.

For approved products, such as Symvess, the FDA and other regulatory authorities may limit the scope of that approval, require us to include detailed warnings and/or contraindications in product labeling, and/or implement a REMS, which may include restrictions on distribution or use of the product.

If serious safety concerns emerge after product approval, FDA and other regulatory authorities may take steps to withdraw the product from the market.

Any of these events could cause us to delay, abandon or limit the development and, if approved, marketing of our product candidates.

Any of these events could cause us to delay, abandon or limit the development and marketing of Symvess and our product candidates, if approved.

For more information, see the section of this Annual Report on Form 10-K titled “Business."

We may experience delays or difficulties in the enrollment of patients in our clinical trials, which may delay or prevent additional clinical trials and our receipt of necessary marketing approvals.

We are currently enrolling patients in several clinical trials, including in our V012 trial, which is a Phase 3 clinical trial comparing the safety and efficacy of our 6 millimeter HAV to AV fistula for hemodialysis access in women.

We are currently enrolling patients in several clinical trials, including in our V012 trial, which is a Phase 3 clinical trial comparing the safety and efficacy of our 6 millimeter ATEV to AV fistula for hemodialysis access in women.

Identifying and qualifying patients to participate in clinical trials of our product candidates is critical to our success.

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• size of the patient population and process for identifying subjects;

• availability of clinical trial research resources at clinical sites due to ongoing effects of the COVID-19 pandemic;

• design of the trial protocol;

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• proximity and availability of clinical trial sites for prospective subjects;

• the ongoing impact of the COVID-19 pandemic or future pandemics or similar events on patients’ willingness and ability to participate in clinical trials or on study site policies;

• the impact of pandemics or similar events on patients’ willingness and ability to participate in clinical trials or on study site policies;

• ability to obtain and maintain subject consent;

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If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit or terminate ongoing or planned clinical trials, any of which would have an adverse effect on our business, financial condition, results of operations and prospects.

Lack of experience by investigators and surgeons with our HAVs can lead to incorrect implantation or follow-up procedures which could harm the results of our clinical trials and market acceptance of our HAVs, if approved.

Our HAVs are currently in various stages of preclinical and clinical testing.

We do not have the personnel capacity to directly conduct or manage all of the clinical trials that are necessary for the development of our HAVs.

Lack of experience by investigators and surgeons with our ATEVs can lead to incorrect implantation or follow-up procedures which could harm the results of our clinical trials and market acceptance of Symvess and our product candidates.

Our ATEV product, Symvess, is FDA approved as a vascular conduit for extremity arterial injury when urgent revascularization is needed to avoid imminent limb loss, and autologous vein graft is not feasible.

For other indications, our ATEVs are currently in various stages of preclinical and clinical testing.

We do not have the personnel capacity to directly conduct or manage solely with our own personnel all of the clinical trials that are necessary for the development of further indications for our ATEVs.

Therefore, we rely, and will continue to rely, on third parties to assist us in managing, monitoring and conducting our clinical trials.

Some of the investigators in our clinical trials have not been, and, if our HAVs receive marketing approval, surgeons may not be, previously exposed to the implantation and follow-up procedures related to their use.

As a result, our HAVs may be, and have been in the past, incorrectly implanted and follow-up procedures may be performed incorrectly, resulting in increased interventions or failure of the HAV, and complicating interpretation of clinical trial results.

Our efforts to educate investigators, surgeons and interventionalists regarding the proper techniques for use of our HAVs both during clinical trials and following potential commercialization may be costly, prove unsuccessful and could materially harm our ability to continue the clinical trials or commence marketing of our HAVs.

Regulatory authorities may also seek to impose restrictive labeling or proactive communication obligations on any marketing approval granted for use of our HAVs as a result, which could reduce market acceptance of any of our HAVs that receive marketing approval.

Our near-term prospects are dependent on the success of our 6 millimeter HAV, and if we are unable to successfully develop and commercialize it, our business, operating results and financial condition will be materially harmed.

We currently have no products approved for sale and, while we are developing a number of product candidates, we have invested and continue to invest a substantial portion of our efforts and financial resources in the development of our 6 millimeter HAV.

None of our remaining product geometries and modifications have advanced beyond preclinical development.

As a result, in the near term we are dependent on the success of our 6 millimeter HAV, and if we are unable to successfully develop, obtain marketing approval for, and commercialize it, our business, along with our operating results and financial condition, will be materially harmed.

Even if we succeed with the development of our 6 millimeter HAV, our ability to generate product revenue and become profitable from our 6 millimeter HAV depends on our assumptions regarding the relevant market opportunity and the degree of market acceptance for our products, once approved, for which our estimates may prove inaccurate, and market acceptance in any approved indication, which may never occur.

Some of the investigators in our clinical trials have not been, and, with regard to Symvess, surgeons may not be, previously exposed to the implantation and follow-up procedures related to their use.

As a result, our ATEVs may be, and have been in the past, incorrectly implanted and follow-up procedures may be performed incorrectly, resulting in increased interventions or failure of the ATEV, and complicating interpretation of clinical trial results.

Our efforts to educate investigators, surgeons and interventionalists regarding the proper techniques for use of our ATEVs both during clinical trials and in commercial use may be costly, prove unsuccessful and could materially harm our ability to continue the clinical trials or commence marketing of Symvess.

Regulatory authorities may also seek to impose

restrictive labeling or proactive communication obligations on any marketing approval granted for use of our ATEVs as a result, which could reduce market acceptance of any of our ATEVs that receive marketing approval.

For example, the FDA approved package insert for Symvess contains a boxed warning relating to mid-graft rupture or anastomotic failure.

We may not be successful in our efforts to use our proprietary scientific technology platform to build a pipeline of additional product candidates.

A key element of our strategy is to use our proprietary scientific technology platform to expand our pipeline of HAVs and to progress other product candidates into and through clinical development.

A key element of our strategy is to use our proprietary scientific technology platform to expand our pipeline of ATEVs and to progress product candidates into and through clinical development.

We may not be able to identify or develop future product candidates that are safe and effective.

Even if we are successful in building our pipeline, the potential product candidates that we identify may not be suitable for clinical development, including if they have harmful side

effects or other characteristics that render them unlikely to receive marketing approval or achieve market acceptance.

Even if we are successful in building our pipeline, the potential product candidates that we identify may not be suitable for clinical development, including if they have harmful side effects or other characteristics that render them unlikely to receive marketing approval or achieve market acceptance.

Research programs to identify new product candidates require substantial technical, financial and human resources, and we may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful.

If we do not successfully develop and commercialize additional product candidates based upon our technology, we may have difficulty generating product revenue in the future, which could result in significant harm to our business, prospects, operating results and financial condition and adversely affect our stock price.

Even if our HAVs receive marketing approval in the future for one or more of our product candidates, they may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

Even with the requisite approvals from the FDA in the United States, the European Commission in the EU and other regulatory authorities internationally, the commercial success of our HAVs will depend, in part, on the acceptance of physicians, patients and health care payors, as medically necessary, cost-effective and safe.

Any product that we commercialize may not gain acceptance by physicians, patients, health care payors and others in the medical community due to ethical, social, medical and legal concerns.

If these products do not achieve an adequate level of acceptance, we may not generate significant product revenue and may not become profitable.

The degree of market acceptance of any of our product candidates that receives marketing approval will depend on a number of factors, including:

• the efficacy and potential advantages of our product candidates compared with alternative products or methods, including convenience and ease of administration;

• the prices we charge for our products, if approved;

• the availability of third-party coverage and adequate reimbursement;

• the willingness of the target patient population to try new products and methods and of physicians to use these products and methods;

• the quality of our relationships with patient advocacy groups;

• the strength of marketing and distribution support;

• the availability of the product and our ability to meet market demand;

• the prevalence and severity of any side effects;

• any restrictions on the use of our products, if approved.

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.

The sizes of the market opportunities for Symvess or our product candidates have not been established with precision and are estimates that management believes to be reasonable.

Our estimates of the market opportunity for certain of our product candidates are based on a number of internal and third-party estimates.

Our estimates of the market opportunity for Symvess and certain of our product candidates, if approved, are based on a number of internal and third-party estimates.

While we believe our assumptions and the data underlying these estimates are reasonable, they may be inaccurate or based on imprecise data.

In addition, the assumptions and conditions underlying the estimates may change at any time.

For example, the number of patients who ultimately use our product candidates, if approved by regulatory authorities, and our total market opportunities for such product candidates, will depend on, among other things, pricing and reimbursement, market acceptance of those product candidates and patient access, and may be lower than we estimate.

Additionally, any approval we receive for our product candidates may be based on a narrower definition of the relevant patient population than we have estimated.

Either of these circumstances could materially harm our business, financial condition, results of operations and prospects.

We face and will continue to face substantial competition, which may result in others discovering, developing or commercializing competing products before or more successfully than we do, which may adversely affect our ability to successfully market or commercialize our HAVs.

For example, the number of patients who ultimately use Symvess or our product candidates, if approved by regulatory authorities, and our total market opportunities for Symvess or such product candidates, will depend on, among other things, pricing and reimbursement, market acceptance of those product candidates and patient access, and may be lower than we estimate.

Additionally, the approval we received for Symvess in trauma includes only adults as a vascular conduit for extremity arterial injury when urgent revascularization is needed to avoid imminent limb loss, and autologous vein graft is not feasible.

Any approval that we receive for our product candidates also may be based on a narrower definition of the relevant patient population than we have estimated.

These and similar limitations on future products could materially harm our business, financial condition, results of operations and prospects.

The development and commercialization of new biological products is highly competitive and subject to rapid change and technological advancements.

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 that Symvess will, and that our product candidates would, if approved, 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 to face competition with respect to any additional product candidates that we may seek to develop or commercialize in the future from a variety of sources, including major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies, hospital product-focused companies, as well as public and private universities and research organizations.

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These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, 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.

We plan to seek marketing approval for our HAVs in the United States as a biologic and in the EU as a medicinal product.

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 provide them with further competitive advantage.

We have obtained initial marketing approval for Symvess in the United States for vascular repair in adults with certain extremity trauma injuries.

We plan to seek marketing approval for our product candidates in the United States as biologics and for Symvess and our product candidates in the EU as a medicinal product.

In both the United States and the EU, our competitors may try to market vascular conduits similar to our product candidates as medical devices.

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Our distribution agreement with Fresenius Medical Care imposes obligations on us that may restrict our ability to operate our business in ways we believe to be in our long-term best interest.

We expect to rely on our strategic, global relationship with Fresenius Medical Care for the development and commercialization of certain of our product candidates.

As discussed in more detail in the section of this Annual Report on Form 10-K titled “Business — Distribution — Distribution Agreement with Fresenius Medical Care,” Fresenius Medical Care will have the exclusive right to develop outside of the United States and EU and commercialize outside of the United States, among other things, our 6 millimeter x 42 centimeter HAV and all improvements thereto, and modifications and derivatives thereof (including any changes to the length, diameter, or configuration of the foregoing), which we refer to as the distribution product, for use in vascular creation, repair, replacement or construction (including renal replacement therapy for dialysis access, the treatment of vascular trauma, and the treatment of PAD, 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).

We expect to rely on our strategic, global relationship with Fresenius Medical Care for the development and commercialization of Symvess and certain of our product candidates.

As discussed in more detail in the section of this Annual Report on Form 10-K titled “Business — Distribution — Distribution Agreement with Fresenius Medical Care,” Fresenius Medical Care will have the exclusive right to develop outside of the United States and EU and commercialize outside of the United States, among other things, our 6 millimeter x 42 centimeter ATEV and all improvements thereto, and modifications and derivatives thereof (including any changes to the length, diameter, or configuration of the foregoing), which we refer to as the distribution product, for use in vascular creation, repair, replacement or construction (including renal replacement therapy for dialysis access, the treatment of vascular trauma, and the treatment of PAD, 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).

We refer to these indications wherein Fresenius Medical Care has rights to develop and commercialize Humacyte’s products as the field.

The distribution agreement also imposes a number of restrictions on our business.

For instance, outside the United States, the distribution agreement restricts our ability to engage a distributor for the distribution product outside the field or for HAV products other than the distribution product:

we have granted Fresenius Medical Care (i) an exclusive right of first negotiation for exclusive distribution rights outside the United States for the distribution product for use outside the field, and (ii) an exclusive right of first negotiation for exclusive distribution rights outside the United States for our other HAV products, if any, subject, in each case, to certain conditions.

For instance, outside the United States, the distribution agreement restricts our ability to engage a distributor for the distribution product outside the field or for ATEV products other than the distribution product:

we have granted Fresenius Medical Care (i) an exclusive right of first negotiation for exclusive distribution rights outside the United States for the distribution product for use outside the field, and (ii) an exclusive right of first negotiation for exclusive distribution rights outside the United States for our other ATEV products, if any, subject, in each case, to certain conditions.

These and other obligations may restrict our ability to operate our business in ways we believe are in our long-term best interest, which could harm our business and our prospects.

If we receive approval for a product candidate that is not subject to our distribution agreement with Fresenius Medical Care, and we are unable to establish our own marketing, sales and distribution capabilities or are unable to enter into agreements with third parties do so, we may not be able to generate product revenue and will have to alter our development and commercialization plans.

We recently received FDA approval to commercialize Symvess in the United States.

As a company, we had no prior experience commercializing a product.

We currently have limited internal marketing, sales or distribution capabilities, and our management team has limited experience commercializing products following marketing approval.

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Further, whether we commercialize any such product candidate on our own or rely on a third party to do so, our ability to generate revenue will be dependent on the effectiveness of the organization performing these functions.

Even if we receive marketing approval for our HAVs, there is uncertainty with respect to third-party coverage and reimbursement of our HAVs.

There is uncertainty with respect to third-party coverage and reimbursement of Symvess and our product candidates, if approved.

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.

There is uncertainty around third-party coverage and reimbursement of newly approved regenerative medicine type products, even those with the RMAT designation from FDA, such as our 6 millimeter HAV for urgent arterial repair following extremity vascular trauma, which received the RMAT designation in 2023, and our 6 millimeter HAV for AV access for performing hemodialysis, which received the RMAT designation in 2017.

There is uncertainty around third-party coverage and reimbursement of newly approved regenerative medicine type products, including Symvess.

In the United States, third-party payors, including government payors such as the Medicare and Medicaid programs, play an important role in determining the extent to which medical products and biologics will be covered and reimbursed.

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Currently, no RMAT tissue engineered product has established coverage and reimbursement by the CMS.

Even if our HAVs receive approval from regulatory authorities, it is difficult to predict what CMS or any comparable foreign regulatory agency will decide with respect to coverage and reimbursement for novel products such as ours, as there is no body of established practices and precedents for these types of products.

It is difficult to predict what CMS or any comparable foreign regulatory agency will decide with respect to coverage and reimbursement for novel products such as Symvess or our product candidates, as there is no body of established practices and precedents for these types of products.

The healthcare industry is acutely focused on cost containment, both in the United States and elsewhere.

Government authorities and third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement.

These payors may not view our products, if any, as cost-effective, and coverage and reimbursement may not be available to our customers or may not be sufficient to allow our products, if any, to be marketed on a competitive basis.

Cost-control initiatives could also cause us to decrease any price we might establish for products, which could result in lower than anticipated product revenue.

Moreover, eligibility for reimbursement does not imply that any product will be paid for in all cases or at a rate that covers our costs, including our costs related to research, development, manufacture, sale and distribution.

Reimbursement rates may vary, by way of example, according to the use of the product and the clinical setting in which it is used.

These payors may not view Symvess and our other products, if approved, as cost-effective, and coverage and reimbursement may not be available to our customers or may not be sufficient to allow our products to be marketed on a competitive basis.

Cost control initiatives could also cause us to decrease any price we might establish for our products, which could result in lower than anticipated product revenue.

Moreover, eligibility for reimbursement does not imply that any such product will be paid for in all cases or at a rate that covers our costs, including our costs related to research, development, manufacture, sale and distribution.

Reimbursement rates may vary, by way of example, according to the use of Symvess or our other products, if approved, and the clinical setting in which it is used.

If the prices for our products, if any, decrease or if governmental and other third-party payors do not provide adequate coverage or reimbursement, our business, prospects, operating results and financial condition will suffer, perhaps materially.

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The IRA contains statutory exclusions to the negotiation program, including for certain orphan designated drugs for which the only approved indication (or indications) is for the orphan disease or condition.

Should our product candidates be approved and covered by Medicare Part B or Part D, and fail to fall within a statutory exclusion, such as that for an orphan drug, those products could, after a period of time, be selected for negotiation and become subject to prices representing a significant discount from average prices to wholesalers and direct purchasers.

Should Symvess or our other products, if approved, be covered by Medicare Part B or Part D, and fail to fall within a statutory exclusion, such as that for an orphan drug, Symvess or our other products could, after a period of time, be selected for negotiation and become subject to prices representing a significant discount from average prices to wholesalers and direct purchasers.

The IRA also establishes a rebate obligation for drug manufacturers that increase prices of Medicare Part B and Part D covered drugs at a rate greater than the rate of inflation.

The inflation rebates

may require us to pay rebates if we increased the cost of a covered Medicare Part B or Part D approved product faster than the rate of inflation.

The inflation rebates may require us to pay rebates if we increase the cost of a product covered by Medicare Part B or Part D faster than the rate of inflation.

In addition, the law eliminates the “donut hole” under Medicare Part D beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and requiring manufacturers to subsidize, through a newly established manufacturer discount program, 10% of Part D enrollees’ prescription costs for brand drugs below the out-of-pocket maximum and 20% once the out-of-pocket maximum has been reached.

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If reimbursement of our products, if approved, is unavailable or more limited in scope or amount than we anticipate, or if pricing is set at even lower levels than we anticipate, our business could be harmed, possibly materially.

Product liability lawsuits against us could cause us to incur substantial liabilities that may not be covered by our limited product liability insurance and may limit the development, approval and commercialization of our HAVs and any other product candidates that we develop in the future.

We face an inherent risk of product liability exposure related to the testing of our product candidates in human clinical trials and will face an even greater risk, if and when we commercially sell our HAVs and any other product candidates that we may develop.

If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we will incur substantial liabilities.

Product liability lawsuits against us could cause us to incur substantial liabilities that may not be covered by our limited product liability insurance and may limit the development, approval and commercialization of Symvess and any product candidates that we develop in the future.

We face an inherent risk of product liability exposure related to the testing of Symvess and our product candidates in human clinical trials.

As we begin to sell Symvess, we will face an even greater risk of such exposure.

If we cannot successfully defend ourselves against claims that Symvess or our product candidates caused injuries, we will incur substantial liabilities.

Regardless of merit or eventual outcome, product liability claims may result in:

• decreased demand for any product candidates or products that we develop or sell, leading to loss of revenue;

• decreased demand for Symvess or any product candidates that we develop or sell, leading to loss of revenue;

• injury to our reputation and significant negative media attention;

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• substantial monetary awards to trial participants or patients;

• inability to further develop or commercialize our product candidates.

• inability to further develop or commercialize Symvess or our product candidates.

We currently hold limited product liability insurance coverage, and it may not be adequate to cover all liabilities that we may incur.

We also may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.

Risks Related to Manufacturing Our Product Candidates

The manufacture of our product candidates is complex, we have not manufactured commercial product, and we have in the past and may in the future encounter difficulties in production.

The process of manufacturing our HAVs is complex, highly regulated and subject to multiple risks.

The manufacture of biologics such as our HAVs has been, and continues to be, susceptible to product loss due to a range of factors including contamination, equipment failure, temporary power outages, improper installation or operation of equipment, damage to facilities, vendor or operator error, inconsistency in yields, variability in product characteristics and difficulties in scaling the production process.

Even minor deviations from normal manufacturing processes has resulted, and could in the future result, in reduced production yields, product defects and other supply disruptions.

If microbial, viral or other contaminations are discovered in our product candidates or in the manufacturing facilities in which our product candidates are made, manufacturing may be delayed for an extended period of time to investigate and remedy the contamination, which would harm our business, operating results and financial condition as well as our reputation.

We depend on cell banks in our manufacturing process, and the loss of our master cell banks would result in significant disruptions to that process.

We currently manufacture the 6 millimeter HAVs for our clinical trials at our manufacturing facility in Durham, North Carolina, where we have created a scalable modular manufacturing process, which we refer to as the LUNA200 system, that we believe will enable us to manufacture our HAVs, if approved, in commercial quantities in compliance with cGMPs.

Risks Related to Manufacturing Symvess and Our Product Candidates

The manufacture of Symvess and our product candidates is complex, we have limited experience manufacturing commercial product, and we have in the past and may in the future encounter batch failures and difficulties in production.

If we or any third-party supplier encounter such difficulties, our ability to supply Symvess for commercial sale or our product candidates for clinical trials could be delayed or halted entirely.

The process of manufacturing our ATEV s, including Symvess, is complex, highly regulated and subject to multiple risks.

The manufacture of biologics such as our ATEV s has been, and continues to be, susceptible to product loss and batch failures due to a range of factors including raw material and other component deficiencies, contamination, equipment failure, temporary power outages, improper installation or operation of equipment, damage to facilities, vendor or operator error, inconsistency in yields, variability in product and raw material characteristics and difficulties in scaling the production process.

Even minor deviations from normal manufacturing processes has resulted, and could in the future result, in reduced production yields, batch failures, product defects and other supply disruptions.

For example, from time to time we have had multiple batch failures in succession.

We believe we have identified the root cause of those failures and have implemented appropriate corrective actions.

However, if our corrective actions are not successful, or if the FDA disagrees with our root cause analysis or our corrective actions, it may delay or disrupt our manufacturing operations or delay or prevent the filing or approval of marketing applications for our ATEV s.

If microbial, viral or other contaminations are discovered in Symvess or our product candidates, or in the manufacturing facilities in which our products are made, manufacturing may be delayed or disrupted for an extended period of time to investigate and remedy the contamination, which would harm our business, operating results and financial condition as well as our reputation.

We depend on cell banks in our manufacturing process, and the loss or alteration of our master cell banks would result in significant disruptions to that process.

We currently manufacture Symvess for initial commercial distribution and our 6 millimeter ATEV s for our clinical trials at our manufacturing facility in Durham, North Carolina, where we have created a scalable modular manufacturing process, which we refer to as the LUNA200 system, that we believe will enable us to manufacture Symvess in commercial quantities in compliance with cGMPs.

Our efforts to scale out our manufacturing operations may not succeed.

Scaling out a biologic manufacturing process is a difficult task, as there are risks including, among others, cost overruns, process reproducibility, stability issues, lot consistency and timely availability of raw materials.

We have limited years of experience manufacturing our HAVs in-house with the LUNA200 system, and no experience manufacturing the volume that we anticipate will be required to supply all of our clinical trials or to achieve planned levels of commercial sales following marketing approval, if received.

We have limited years of experience manufacturing our ATEV s in-house with the LUNA200 system, and no experience manufacturing the volume of Symvess and our ATEV product candidates that we anticipate will be required to achieve planned levels of commercial sales and to supply all of our clinical trials.

Additionally, our manufacturing process has evolved over time and we may not have the experience, resources, or facility capacity to handle adoption of future changes or expansion of capacity.

The forecasts of demand we plan to use to determine order quantities and lead times for components from outside suppliers may be incorrect, and we may be unable to obtain such components when needed and at a reasonable cost.

We also have experienced interruptions in the supply of the raw materials required to manufacture our product candidates, and increased costs due to supply chain disruptions or inflation in the cost of goods, services or other operating inputs.

Likewise, supply chain interruptions could affect the transport of clinical trial materials, such as our HAVs and other supplies used in our clinical trials, which would negatively impact our ability to conduct our clinical trials.

In addition, we may not be able to develop and implement efficient manufacturing capabilities and processes to manufacture our HAVs in sufficient volumes that also satisfy the legal, regulatory, quality, price, durability, engineering, design and production standards required to commercialize our HAVs successfully.

If we are unable to produce sufficient quantities of our HAVs for our clinical trial needs or commercialization, we may need to make additional changes to our manufacturing processes and procedures.

We also have experienced interruptions in the supply of the raw materials required to manufacture our products, and increased costs due to supply chain disruptions or inflation in the cost of goods, services or other operating inputs.

Likewise, supply chain interruptions could affect the transport of Symvess or our clinical trial materials, such as our investigational ATEV s and other supplies, which would negatively impact our ability to conduct our clinical trials or commercialize our product.

In addition, we may not be able to develop and implement efficient manufacturing capabilities and processes to manufacture our ATEV s in sufficient volumes that also satisfy the legal, regulatory, quality, price, durability, engineering, design and production standards required to commercialize our ATEV s, including Symvess, successfully.

If we are unable to produce sufficient quantities of Symvess for commercialization or our investigational ATEV s for our clinical trial needs, we may need to make additional changes to our manufacturing processes and procedures.

Such changes to our manufacturing platform could trigger the need to conduct additional bridging studies between our prior clinical supply and that of any new manufacturing processes and procedures.

Should we experience delays or be unable to produce sufficient quantities of our HAVs utilizing our current or a modified version of our manufacturing system, we expect that our development and commercialization efforts would be impaired as a result, which would likely materially adversely affect our business, prospects, operating results and financial condition.

Should we experience delays or be unable to produce sufficient quantities of our ATEV s, including Symvess, utilizing our current or a modified version of our manufacturing system, we expect that our development and commercialization efforts would be impaired as a result, which would likely materially adversely affect our business, prospects, operating results and financial condition.

Manufacturing facilities are subject to significant government regulations and approvals, which are often costly and could result in adverse consequences to our business if we fail to comply with the regulations or maintain the approvals.

Our manufacturing facility is subject to ongoing regulation and periodic inspection by the FDA and other regulatory authorities to ensure compliance with cGMPs.

Failure to follow and document adherence to such regulations or other regulatory requirements may (i) lead to significant delays in the availability of product for our clinical trials, (ii) result in the termination of or a hold being placed on one or more of our clinical trials, (iii) require significant modifications to our manufacturing facility, personnel, and procedures, (iv) delay or prevent filing or approval of marketing applications for our HAVs, (v) result in temporary or permanent closures of our manufacturing facilities, and/or (vi) result in other civil or criminal penalties.

Failure to follow and document adherence to such regulations or other regulatory requirements may (i) lead to significant delays in the availability of Symvess for commercial sale or of product for our clinical trials, (ii) result in the termination of or a hold being placed on one or more of our clinical trials, (iii) require significant modifications to our manufacturing facility, personnel, and procedures, (iv) delay or prevent filing or approval of marketing applications for our product candidates, (v) result in temporary or permanent closures of our manufacturing facilities, and/or (vi) result in other civil or criminal penalties.

Risks Related to Our Reliance on Third Parties

We rely on third parties to conduct and support our clinical trials, and those third parties may not perform satisfactorily, including by failing to adhere to regulatory requirements or our stated protocols or to meet deadlines for the completion of such trials.

We do not independently conduct clinical trials for our product candidates and instead rely on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, to perform various functions, including implanting our HAVs and monitoring patients.

The FDA and other regulatory authorities require us and these third parties to comply with GCP and, where applicable, cGTPs for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of patients in clinical trials are protected;

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Failure by us or these third parties to do so could require us to enroll additional trial subjects beyond those we anticipate, could require us to modify our protocol, which may cause us to lose previously established Special Protocol Assessment (“SPA”) agreements with the FDA or similar agreements with other regulatory authorities concerning whether the design and size of our clinical trial adequately addresses scientific and regulatory requirements to support marketing approval, or could materially harm our ability to complete our clinical trials, including as a result of the need to remove trial sites and participants from the trial, and could result in civil or criminal penalties.

We have in the past and may in the future need to terminate trial sites due to failure to conduct a trial in accordance with its protocol, applicable regulations, GCPs, and generally accepted research standards.

The performance of the sites for our clinical trials may also be adversely affected by various other issues, including the lack of familiarity with the properties of our HAVs, intervention rates, insufficient training of personnel, variances in medical infrastructure, lack of familiarity with conducting clinical trials in accordance with international regulatory standards, communication difficulties or changes in local regulations.

If these third parties do not successfully conduct our clinical trials in accordance with regulatory requirements or our stated protocols, carry out their contractual duties, or meet expected deadlines, we may not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates and may not be able to, or may be delayed in our efforts to, successfully commercialize our products if approved by regulatory authorities.

We rely on third-party suppliers, including sole source suppliers, to provide certain components for our product candidates.

Any failure by a third-party supplier to supply these components for manufacture may delay or impair our ability to complete our clinical trials and to commercialize our product candidates.

We currently rely, and expect to continue to rely, on third parties for the supply of certain components necessary for our product candidates, such as donor tissue, other biologically derived substances, the PGA polymer mesh and the bioreactor bags in which our HAVs are grown.

We have in the past and may in the future need to terminate trial sites due to

failure to conduct a trial in accordance with its protocol, applicable regulations, GCPs, and generally accepted research standards.

The performance of the sites for our clinical trials may also be adversely affected by various other issues, including the lack of familiarity with the properties of our ATEVs, intervention rates, insufficient training of personnel, variances in medical infrastructure, lack of familiarity with conducting clinical trials in accordance with international regulatory standards, communication difficulties or changes in local regulations.

If these third parties do not successfully conduct our clinical trials in accordance with regulatory requirements or our stated protocols, carry out their contractual duties, or meet expected deadlines, we may not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates and may not be able to, or may be delayed in our efforts to, successfully commercialize Symvess or our product candidates, if approved by regulatory authorities.

We rely on third-party suppliers, including sole source suppliers, to provide certain components for Symvess and our product candidates.

Any failure by a third-party supplier to supply these components for manufacture may delay or impair our ability to commercialize Symvess and to complete our clinical trials for our product candidates.

We currently rely, and expect to continue to rely, on third parties for the supply of certain components necessary for Symvess and our product candidates, such as donor tissue, other biologically derived substances, human serum, the PGA polymer mesh and the bioreactor bags in which our ATEVs are grown.

Our suppliers for certain of these materials, including SeraCare for the supply of human plasma and Confluent for the supply of polymer mesh, are sole source suppliers.

Failure of one or more of our suppliers, including these sole source suppliers, to deliver components necessary for the production of our HAVs in a timely and sufficient manner, whether due to shortages of such materials, difficulties in scaling up supply to satisfy our clinical trial and commercial needs, contamination, recall, the COVID-19 pandemic or otherwise, or to source or manufacture such components in accordance with cGMPs and cGTPs, as applicable, could delay our ability to complete our clinical trials, obtain marketing approval and commercialize our product candidates.

Failure of one or more of our suppliers, including these sole source suppliers, to deliver components necessary for the production of our ATEVs in a timely and sufficient manner, whether due to shortages of such materials, difficulties in scaling up supply to satisfy our clinical trial and commercial needs, contamination, recall, pandemics or otherwise, or to source or manufacture such components in accordance with cGMPs and cGTPs, as applicable, could delay our ability to commercialize Symvess, which would reduce revenue from our sole approved product, or to complete our clinical trials, obtain marketing approval for and commercialize our product candidates.

Establishing additional or replacement suppliers for these components could take a substantial amount of time and it may be difficult to establish replacement suppliers who meet regulatory requirements.

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We expect to continue to incur losses for the foreseeable future and may never generate product revenue or be profitable.

Since inception, we have generated no product revenue, and prior to receipt of marketing approval from regulatory authorities, we will be unable to do so.

Since inception, we have generated no product revenue.

We incurred net losses of $148.7 million and $110.8 million for the years ended December 31, 2024 and 2023, respectively.

As of December 31, 2024 and 2023, we had an accumulated deficit of $686.0 million and $537.3 million, respectively.

We have historically financed our operations primarily through the sale of equity securities and convertible debt, proceeds from the Merger and related PIPE Financing, borrowings under loan facilities, the Purchase Agreement and, to a lesser extent, through grants from governmental agencies.

We have historically financed our operations primarily through the sale of equity securities and convertible debt, proceeds from our going public transaction, borrowings under loan facilities, the Purchase Agreement and, to a lesser extent, through grants from governmental agencies.

We have devoted substantially all of our financial resources and efforts to research and development, including preclinical studies and clinical trials and development of manufacturing technology, and we anticipate that our expenses will continue to increase over the next several years as we continue these activities.

To become and remain profitable, we must succeed in obtaining marketing approval for our HAVs in the United States, in commercializing our HAVs, and in developing and commercializing additional product candidates that generate significant revenue.

To become and remain profitable, we must succeed in commercializing Symvess, obtaining marketing approval for Symvess outside of the United States, obtaining marketing approval for our product candidates, and in developing and commercializing additional product candidates that generate significant revenue.

We may never succeed in these activities and, even if we do, may never generate revenue that is sufficient to achieve profitability.

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We expect to need to raise additional funding, which may not be available on acceptable terms, or at all, and any failure to obtain capital when needed may force us to delay, limit or terminate our product development or commercialization efforts.

We expect to incur significant expenses in connection with our ongoing activities as we seek to (i) scale out our manufacturing facility to satisfy potential demand if our HAVs receive marketing approval in the United States, (ii) continue our preclinical and clinical development efforts, including the ongoing clinical trials, and (iii) obtain marketing approval for our 6 millimeter HAV, and, if marketing approval is obtained, to commercialize our HAVs for one or more approved indications.

We expect to incur significant expenses in connection with our ongoing activities as we seek to (i) scale out our manufacturing facility to satisfy potential demand for Symvess in the United States, (ii) continue our preclinical and clinical development efforts, including the ongoing clinical trials, and (iii) to commercialize Symvess in the United States and to obtain marketing approval for our 6 millimeter ATEV outside of the United States for one or more approved indications.

We will need additional funding in connection with these activities.

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• the progress and results of our clinical trials and interpretation of those results by the FDA and other regulatory authorities;

• the cost, timing and outcome of regulatory review of our product candidates, particularly for approval of our HAVs in the United States;

• the cost, timing and outcome of regulatory review of our product candidates, particularly for approval of Symvess outside of the United States and of our product candidates in the United States;

• the scope, progress, results and costs of preclinical development, laboratory testing and clinical trials for our additional product candidates;

• the cost and timing of our future commercialization activities, including product manufacturing, marketing and distribution for our HAVs if approved by the FDA, and any other product candidate for which we receive marketing approval in the future;

• the amount and timing of revenues, if any, that we receive from commercial sales of any product candidates for which we receive marketing approval;

• the cost and timing of our future commercialization activities, including product manufacturing, marketing and distribution for Symvess in the United States, and any other product candidate for which we receive marketing approval in the future;

• the amount and timing of revenues, if any, that we receive from commercial sales of Symvess and any product candidates for which we receive marketing approval;

• the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims.

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If we are unable to raise capital, we could be forced to delay, reduce, suspend or cease our research and development programs or any future commercialization efforts, which would have a negative impact on our business, prospects, operating results and financial condition.

As of December 31, 2023, we had cash and cash equivalents of $80.4 million and as of December 31, 2022, we had cash and cash equivalents and short-term investments of $151.9 million.

Subsequent to December 31, 2023, in March 2024 we completed the Offering (defined below), which provided approximately $43.1 million in net proceeds and received an additional $20.0 million under the Purchase Agreement (defined below).

As of December 31, 2024, we had cash and cash equivalents of $44.9 million and restricted cash of $50.4 million , and as of December 31, 2023, we had cash and cash equivalents of $80.4 million and restricted cash of $0.4 million.

Subsequent to December 31, 2024, in March 2025 we completed a public offering of common stock which provided approximately $46.6 million in net proceeds.

Based upon our current operating plan, we believe that our cash and cash equivalents will be sufficient to fund our operations, including clinical trial expenses and capital expenditure requirements, for at least 12 months from the date of this Annual Report on Form 10-K.

Pursuant to the terms of the Purchase Agreement, we may be limited in our ability to incur future debt.

On May 12, 2023, the Company and Global entered into the Purchase Agreement with the Purchasers and another affiliate of Oberland, as agent for the Purchasers (the “Agent”), to obtain financing with respect to the further development and commercialization of the Company’s HAV, to repay the Company’s credit facility with Silicon Valley Bank (“SVB”), and for other general corporate purposes.

On May 12, 2023, the Company and Global entered into the Purchase Agreement with the Purchasers and another affiliate of Oberland, as agent for the Purchasers (the “Agent”), to obtain financing with respect to the further development and commercialization of the Company’s ATEV, to repay the Company’s credit facility with Silicon Valley Bank (“SVB”), and for other general corporate purposes.

Pursuant to the terms of the Purchase Agreement, we are limited in our ability to incur additional indebtedness without the prior written consent of the Purchasers.

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We cannot assure you that our business will generate sufficient cash flow from operations, that we will be able to incur future debt on favorable terms or at all, or that future financing will be available to us in amounts sufficient to fund our operations.

To date, we have not obtained marketing approval for, or commercialized, any of our product candidates, which may make it difficult for you to evaluate the success of our business to date and to assess our future viability.

We are a development-stage company.

To date, we have obtained marketing approval for, and begun commercializing, only one product, which may make it difficult for you to evaluate the success of our business to date and to assess our future viability.

We recently began commercializing Symvess, our sole approved product in the United States.

Our operations to date, with respect to the development of our product candidates, have been limited to organizing and staffing our company, business planning, raising capital, identifying markets for our product candidates, undertaking preclinical studies and clinical trials of our product candidates for various potential indications and establishing research and development, manufacturing and distributing collaborations.

We have not yet demonstrated the ability to obtain marketing approval for a product, to manufacture an approved product at commercial scale or to successfully commercialize an approved product.

Consequently, any predictions you make about our financial prospects may not be as accurate as they could be if we had received marketing approval and begun commercializing a product.

We have not yet demonstrated the ability to manufacture an approved product at commercial scale or to successfully commercialize an approved product.

Consequently, any predictions you make about our financial prospects may not be as accurate as they could be if we already had commercialized a product.

Risks Related to Government Regulation

Even though we received marketing approval for Symvess, we continue to be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense and subject us to significant penalties if we fail to comply with applicable regulatory requirements.

Symvess and any other product candidates for which we also obtain marketing approval in the United States, will be subject to ongoing regulatory requirements from the FDA and, if approved elsewhere, from applicable non-U.S.

regulatory authorities.

Any marketing approval that we receive for our product candidates may be subject to limitations on the indicated uses for which the product may be marketed or contain requirements for potentially costly post-marketing follow-up trials to monitor the safety and efficacy of the product.

For example, the FDA’s approval of Symvess includes requirements to conduct an open-label study to assess the safety and efficacy of Symvess in certain patients 17 years of age or younger, as well as a long-term observational study to further characterize the risk of graft failure and infection in patients with extremity vascular injury who have received Symvess for the approved indication.

The FDA could also approve our product candidates with a REMS, which could include significant restrictions on distribution and/or use of our products.

In addition, we are subject to extensive and ongoing post-approval regulatory requirements for Symvess by the FDA, and if approved elsewhere, by other non-U.S.

regulatory authorities, with regard to the manufacturing, labelling, packaging, AE reporting, storage, advertising, distribution, promotion and recordkeeping for Symvess and any other product candidates that may receive marketing approval.

If we fail to comply with regulatory requirements of the FDA and, if relevant, other non-U.S.

regulatory authorities, we could be subject to administrative or judicially imposed sanctions, including the following:

• issuance of warning letters or untitled letters by regulatory authorities asserting that we are in violation of the law;

• imposition of injunctions or significant civil monetary penalties or pursuit by regulatory authorities of civil or criminal prosecutions and fines or other civil and/or criminal penalties against us or our responsible officers;

• suspension or withdrawal of marketing approval;

• suspension of any ongoing clinical trials or refusal by regulatory authorities to approve pending marketing applications or supplements to approved applications;

• seizure of products or refusal to allow us to enter into supply contracts, including government contracts, or to import or export products;

• voluntary or mandatory product recalls and publicity requirements;

• restrictions on operations, including marketing efforts, or restrictions that mandate costly new manufacturing requirements.

Any of these events could reduce market acceptance of Symvess or any of our product candidates that had received marketing approval, substantially reduce our revenue, increase the costs of operating our business, and cause us significant reputational damage, among other consequences.

If we ultimately receive approval for Symvess or any of our product candidates in jurisdictions outside the United States, we expect to be subject to similar ongoing regulatory oversight by the relevant foreign regulatory authorities.

Our products may be subject to product recalls that could harm our reputation and could materially and adversely affect our business, financial condition, operating results, cash flows and prospects.

The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about approved products.

In particular, while the FDA permits the dissemination of truthful and non-misleading information about an approved product, the FDA restricts our ability to promote a product for uses that are not approved by the FDA.

The misuse or off-label use of our product may harm our reputation in the marketplace, result in injuries that lead to product liability suits or result in costly investigations, fines or sanctions by regulatory authorities if we are deemed to have engaged in the promotion of these uses, any of which could be costly to our business.

We may also face risks in other non-U.S.

jurisdictions from product recalls and advertising/promotion rules.

We could also face product liability suits or regulatory delays due to defects in our products, which could be expensive and time-consuming and result in substantial damages payable by us and increases in our insurance rates.

We may not obtain marketing approval from the FDA for any of our product candidates even if we successfully complete our clinical trials, which failure would materially harm our business, prospects, operating results and financial condition.

Prior to commercialization, biologics, like our HAVs, require the submission of a BLA to, and approval of the BLA by, the FDA.

Prior to commercialization, biologics, like our ATEVs, require the submission of a BLA to, and approval of the BLA by, the FDA.

A BLA must be supported by extensive preclinical and clinical data, as well as extensive information regarding chemistry, manufacturing and controls (“CMC”), sufficient to demonstrate the safety, purity, potency and effectiveness of the applicable product candidate to the satisfaction of the FDA.

In February 2024, the FDA accepted and granted priority review for our first BLA seeking approval of our HAV for urgent arterial repair following extremity vascular trauma when synthetic graft is not indicated and autologous vein use is not feasible, but there can be no assurance that we will obtain FDA approval for that indication or for any of our product candidates.

The BLA approval process is expensive and uncertain, it may take several years to complete, and we may not be successful in obtaining such approval.

In December 2024, the FDA approved Symvess as a vascular conduit for extremity arterial injury when urgent revascularization is needed to avoid imminent limb loss, and autologous vein graft is not feasible, but there can be no assurance that we will obtain approval outside of the United States for that indication or marketing approval for any of our product candidates.

The BLA approval process is expensive and uncertain, it may take several years to complete, and we may not be successful in obtaining approval for our product candidates.

The FDA has substantial discretion in the approval process and decisions made by the FDA can be unpredictable.

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Even highly significant and favorable clinical trial results are no guarantee of approval.

Even if we obtain and maintain approval for our HAVs from the FDA, we may never obtain approval for our HAVs outside of the United States, where the regulatory process is also complex and subject to significant uncertainty.

Even though we obtained approval for Symvess from the FDA, we may never obtain approval for our ATEVs outside of the United States, where the regulatory process is also complex and subject to significant uncertainty.

Failure to do so would limit our market opportunities and adversely affect our business.

Even if we receive FDA approval to market any biologic in the United States, we must comply with the numerous and varying regulatory and compliance related requirements of other countries, including the submission of extensive preclinical and clinical data, manufacturing and quality information regarding the process and facility, scientific data characterizing the relevant product candidate and other supporting data in order to establish safety and effectiveness.

Even though we received FDA approval to market Symvess in the United States, we must comply with the numerous and varying regulatory and compliance related requirements of other countries, including the submission of extensive preclinical and clinical data, manufacturing and quality information regarding the process and facility, scientific data characterizing the relevant product candidate and other supporting data in order to establish safety and effectiveness.

Approval procedures vary among countries and can involve additional product testing and additional administrative review periods, including obtaining reimbursement and pricing approval in select markets.

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The marketing approval process for novel product candidates such as ours may take longer to complete and be more expensive than the process for other, better known or extensively studied pharmaceutical or other product candidates.

On December 12, 2023, we submitted our BLA for the HAV in urgent arterial repair following extremity vascular trauma when synthetic graft is not indicated and autologous vein use is not feasible.

On December 12, 2023, we submitted our BLA for the ATEV in urgent arterial repair following extremity vascular trauma when synthetic graft is not indicated and autologous vein use is not feasible.

We submitted our BLA using a “rolling review,” which means we may submit completed modules of a BLA rather than waiting until every module of the BLA is completed before submitting the full BLA for FDA review.

Such “rolling review” is common for indications that are part of one of FDA’s expedited programs, such as our 6 millimeter HAV, which has received Fast Track and RMAT designations for AV access in hemodialysis, and RMAT designation for urgent arterial repair following extremity vascular trauma.

Such “rolling review” is common for indications that are part of one of FDA’s expedited programs, such as our 6 millimeter ATEV, which has received Fast Track and RMAT designations for AV access in hemodialysis, and RMAT designation for urgent arterial repair following extremity vascular trauma.

In February 2024, the FDA accepted our BLA in the vascular trauma indication and granted priority review of that BLA.

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We are not permitted to commercialize our product candidates in the United States until they have been approved by the FDA, and if we experience a lengthier review period than expected, our ability to generate product revenues would be materially harmed.

We may in the future seek orphan drug designation for the use of our HAVs to treat congenital pediatric heart defects.

We may in the future seek orphan drug designation for the use of our ATEVs to treat congenital pediatric heart defects.

We may be unable to obtain such designation or to maintain the benefits associated with orphan drug designation, including market exclusivity, which may cause our revenue, if any, to be reduced.

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Inadequate funding for the FDA and other government agencies, including from government shut downs, global health concerns or other disruptions to these agencies’ operations, could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.

The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and statutory, regulatory, policy changes, and the effects of the COVID-19 pandemic.

Average review times at the FDA have fluctuated in recent years as a result.

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Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

Even if we receive marketing approval for a product candidate, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense and subject us to significant penalties if we fail to comply with applicable regulatory requirements.

If we obtain marketing approval for any of our product candidates, the approved product will be subject to ongoing regulatory requirements from the FDA and, if applicable, non-U.S.

regulatory authorities.

The FDA could also approve our product candidates with a REMS, which could include significant restrictions on distribution and/or use of our products.

In addition, if the FDA and non-U.S.

regulatory authorities approve any of our product candidates, we will be subject to extensive and ongoing regulatory requirements by the FDA and other regulatory authorities with regard to the manufacturing, labelling, packaging, AE reporting, storage, advertising, distribution, promotion and recordkeeping for our products.

If we, our product candidates or the manufacturing facilities for our product candidates fail to comply with regulatory requirements of the FDA and, if relevant, other non-U.S.

regulatory authorities, we could be subject to administrative or judicially imposed sanctions, including the following:

• issuance of warning letters or untitled letters by regulatory authorities asserting that we are in violation of the law;

• suspension or withdrawal of marketing approval;

• suspension of any ongoing clinical trials or refusal by regulatory authorities to approve pending marketing applications or supplements to approved applications;

• seizure of products or refusal to allow us to enter into supply contracts, including government contracts, or to import or export products;

• voluntary or mandatory product recalls and publicity requirements;

• restrictions on operations, including marketing efforts, or restrictions that mandate costly new manufacturing requirements.

Any of these events could reduce market acceptance of any or our product candidates that had received marketing approval, substantially reduce our revenue, increase the costs of operating our business, and cause us significant reputational damage, among other consequences.

If we ultimately receive approval for any product candidates in jurisdictions outside the U.S., we expect to be subject to similar ongoing regulatory oversight by the relevant foreign regulatory authorities.

Our products may be subject to product recalls that could harm our reputation and could materially and adversely affect our business, financial condition, operating results, cash flows and prospects.

The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products, if approved.

We may also face risks in other non-U.S.

jurisdictions from product recalls and advertising/promotion rules.

Designation of our product candidates for expedited programs, such as Fast Track designation, Breakthrough Therapy Designation, or RMAT designation, or accelerated approval by the FDA, or priority designation by the Department of Defense, may not lead to a faster development or regulatory review or approval process, and even if granted, will not increase the likelihood that our product candidates will receive marketing approval.

In 2014, the FDA granted Fast Track designation for our 6 millimeter HAV for use in the creation of AV access for hemodialysis, in 2017, the FDA granted RMAT designation for our 6 millimeter HAV for the creation of vascular access for performing hemodialysis and in 2023, the FDA granted RMAT designation for our 6 millimeter HAV for urgent arterial repair following extremity vascular trauma.

We have not received designations pursuant to any of the FDA’s expedited programs for PAD or our other indications, although we may in the future seek such designations if such product candidates meet the criteria for that designation.

In 2014, the FDA granted Fast Track designation for our 6 millimeter ATEV for use in the creation of AV access for hemodialysis, in 2017, the FDA granted RMAT designation for our 6 millimeter ATEV for the creation of vascular access for performing hemodialysis, in 2023, the FDA granted RMAT designation for our 6 millimeter ATEV for urgent arterial repair following extremity vascular trauma, and in 2024, the FDA granted RMAT designation for the ATEV for patients with advanced PAD.

We have not received designations pursuant to any of the FDA’s expedited programs for our other indications, although we may in the future seek such designations if such product candidates meet the criteria for that designation.

In addition, even with one or more of these designations, we may not experience a faster development process, or faster review or approval, for our product candidates compared to product candidates that are not part of the expedited programs.

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The loss of a designation under an expedited program, including a Fast Track designation, Breakthrough Therapy Designation, or RMAT designation, could significantly increase the costs of development and length of time required before we could seek marketing approval of such a product candidate.

In addition, in 2018, our HAV product candidate was assigned a priority designation by the Secretary of Defense under Public Law 115-92.

In addition, in 2018, our ATEV product candidate was assigned a priority designation by the Secretary of Defense under Public Law 115-92.

Similar to the designations described above that FDA may grant, a priority designation by the Department of Defense does not change the standards for approval but may expedite the development or approval process.

Healthcare reform measures could hinder or prevent our product candidates’ commercial success.

Our industry is highly regulated, and changes in or revisions to laws and regulations that make gaining coverage of and adequate reimbursement for our product candidates more difficult or subject to different criteria and standards may adversely impact our business, prospects, operating results and financial condition.

In the United States, there have been and we expect there will continue to be a number of legislative, regulatory and other changes to the healthcare system to contain or reduce healthcare costs that may adversely affect our ability to set a price we believe is fair for our product candidates, our ability to generate revenues and achieve or maintain profitability, and the availability of capital.

Healthcare reform measures could hinder or prevent commercial success of Symvess or our product candidates.

Our industry is highly regulated, and changes in or revisions to laws and regulations that make gaining coverage of and adequate reimbursement for Symvess or our product candidates more difficult or subject to different criteria and standards may adversely impact our business, prospects, operating results and financial condition.

In the United States, there have been and we expect there will continue to be a number of legislative, regulatory and other changes to the healthcare system to contain or reduce healthcare costs that may adversely affect our ability to set a price we believe is fair for Symvess or our product candidates, our ability to generate revenues and achieve or maintain profitability, and the availability of capital.

Federal and state lawmakers regularly propose and, at times, enact legislation that would result in significant changes to the healthcare system, some of which are intended to contain or reduce the costs of medical products and services.

At the federal level, for example, the Inflation Reduction Act of 2022, or IRA, was signed into law on August 16, 2022.

Among other key provisions, the IRA:

At the federal level, the Inflation Reduction Act of 2022, or IRA:

• Requires manufacturers to pay rebates for a Medicare Part B or Part D drug if the price increases for the drug exceed the rate of inflation.

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The IRA is anticipated to have significant effects on the pharmaceutical industry and may reduce the prices pharmaceutical manufacturers can charge and the reimbursement pharmaceutical manufacturers can receive for approved products, among other effects.

The Biden administration has indicated that lowering prescription drug prices is a priority.

Lowering prescription drug prices was a stated priority of the Biden administration.

On October 14, 2022, President Biden signed an executive order to lower prescription drug costs for Americans.

In response to this directive, the Center for Medicare and Medicaid Innovation is developing new models intended to lower drug costs under Medicare and Medicaid.

In response to this directive, the Center for Medicare and Medicaid Innovation developed new models intended to lower drug costs under Medicare and Medicaid.

These models include designing new payment methods for drugs approved under accelerated approval to encourage timely confirmatory trial completion and improve access to post-market safety and efficacy data, with the goal of reducing Medicare spending on drugs that have no confirmed clinical benefit;

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Among other things, the executive order directs the HHS Secretary to provide a report on actions to combat excessive pricing of prescription drugs, continue to clarify and improve the approval framework for generic drugs and identify and address any efforts to impede generic drug competition, enhance the domestic drug supply chain, reduce the price that the Federal government pays for drugs, and address price gouging in the industry.

The American Rescue Plan Act of 2021 eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

It is unclear whether these initiatives will be continued or expanded upon in the Trump administration.

The American Rescue Plan Act of 2021 eliminated the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, as of January 1, 2024.

In addition, individual states have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

We cannot predict how further developments of or changes to these laws and regulations will affect our business.

The FDA also released a final rule on September 24, 2020, which went into effect on November 30, 2020, providing guidance for states to build and submit plans for importation of drugs from Canada.

The FDA also released a final rule, effective November 30, 2020, providing guidance for states to build and submit plans for importation of drugs from Canada.

Additionally, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

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In addition, on November 19, 2021, the House of Representatives passed a version of the Build Back Better Act that includes a provision prohibiting the implementation, administration, or enforcement of the rule.

Although a number of these, and other proposed measures may require authorization through additional legislation to become effective, and the Biden administration may reverse or otherwise change these measures, Congress has indicated that it will continue to seek new legislative measures to control drug costs.

Although a number of these, and other proposed measures may require authorization through additional legislation to become effective, and the Trump administration may reverse or otherwise change these measures, Congress has indicated that it will continue to seek new legislative measures to control drug costs.

The ultimate content, timing, or effect of any healthcare reform legislation or executive order or the impact that the resulting changes may have on us is uncertain, but we expect there will continue to be legislative and regulatory proposals at the federal and state levels directed at containing or lowering the cost of health care.

If we fail to comply with healthcare regulations, we could face substantial penalties and our business, prospects, operating results and financial condition could be adversely affected.

Certain federal and state healthcare laws and regulations pertaining to fraud and abuse and patients’ rights are and will be applicable to our business even though we do not and will not control referrals of healthcare services.

Certain federal and state healthcare laws and regulations pertaining to fraud and abuse and patients’ rights are applicable to our business even though we do not and will not control referrals of healthcare services.

We could also be subject to patient privacy regulation by both the U.S.

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

• the federal transparency requirements under the ACA, including the provision commonly referred to as the Physician Payments Sunshine Act and its implementing regulations, which require applicable manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the State Children’s Health Insurance Program to report annually to CMS information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, as well as ownership and investment interests held by the physicians described above and their immediate family members.

Effective January 1, 2022, these reporting obligations were extended to include transfers of value made to certain non-physician providers such as physician assistants and nurse practitioners;

• the federal transparency requirements under the ACA, including the provision commonly referred to as the Physician Payments Sunshine Act and its implementing regulations, which require applicable manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the State Children’s Health Insurance Program to report annually to CMS information related to payments or other transfers of value made to certain health care professionals and teaching hospitals;

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

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Unauthorized disclosure of personally identifiable information could also expose us to sanctions for violations of data privacy laws and regulations around the world.

To the extent that any disruption or security breach resulted in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development of our product candidates could be delayed.

To the extent that any disruption or security breach resulted in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the commercialization of Symvess or the further development of our product candidates could be delayed.

For example, the loss of or damage to clinical trial data, such as from completed or ongoing clinical trials, for any of our product candidates would likely result in delays in our marketing approval efforts and significantly increased costs in an effort to recover or reproduce the data.

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While we have procedures in place for selecting and managing our relationships with third-party service providers and other business partners, we do not have control over their business operations or governance and compliance systems, practices and procedures, and our management of multiple third party service providers increases our operational complexity.

If we fail to adequately monitor our third party service providers’ and partners’ performance,

including for compliance with our agreements and regulatory and legal requirements, we may have to incur additional costs to correct errors, our reputation could be harmed or we could be subject to litigation, claims, legal or regulatory proceedings, inquiries or investigations.

If we fail to adequately monitor our third party service providers’ and partners’ performance, including for compliance with our agreements and regulatory and legal requirements, we may have to incur additional costs to correct errors, our reputation could be harmed or we could be subject to litigation, claims, legal or regulatory proceedings, inquiries or investigations.

These risks may also be present if our third party service providers and partners use separate information systems that are not integrated with our systems and suffer a cybersecurity incident.

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Such threats have increased in frequency, scope and potential impact in recent years, which increase the difficulty of detecting and successfully defending against them.

As cyber threats continue to evolve, we may be required to incur additional expenses in order to enhance our protective measures or to remediate any information security vulnerability.

As cyber threats continue to evolve, we

may be required to incur additional expenses in order to enhance our protective measures or to remediate any information security vulnerability.

There can be no assurance that we or our third-party providers will be successful in preventing cyber-attacks or successfully mitigating their effects.

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It is also possible that unauthorized access to data may be obtained through inadequate use of security controls by our suppliers or other vendors.

In 2021, a remote code execution vulnerability in Apache Log4j was identified as affecting large amounts of systems worldwide.

We were not impacted by the Log4j vulnerability, however we cannot provide assurance that these and other attacks will not have an impact in the future.

Although we have general liability insurance coverage, our insurance may not cover all claims, continue to be available on reasonable terms or be sufficient in amount to cover one or more large claims.

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Failure to comply with health and data protection laws and regulations could lead to government enforcement actions (which could include civil or criminal penalties), private litigation and adverse publicity and could negatively affect our operating results and business.

We and any potential collaborators may be subject to federal, state and foreign data protection laws and regulations ( i.e.

, laws and regulations that address privacy and data security).

We and any potential collaborators may be subject to federal, state and foreign data protection laws and regulations (i.e., laws and regulations that address privacy and data security).

In the United States, numerous federal and state laws and regulations, including federal health information privacy laws, state data breach notification laws, state privacy and health information privacy laws and federal and state consumer protection laws ( e.g.

, Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure and protection of health-related and other personal information could apply to our operations or the operations of our collaborators.

In addition, we may obtain health information from third parties (including research institutions from which we obtain clinical trial data) that are subject to privacy and security requirements under HIPAA.

Depending on the facts and circumstances, we could be subject to civil or criminal penalties if we obtain, use, or disclose individually identifiable health information maintained by a HIPAA-covered entity in a manner that is not authorized or permitted by HIPAA.

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In particular, it is unclear to what extent the UK regime will begin diverging from the GDPR and how data transfers to and from the UK will be regulated.

In addition, California recently enacted the California Consumer Privacy Act (“CCPA”), which creates new individual privacy rights for California consumers (as defined in the law) and places increased privacy and security obligations on entities handling personal data of consumers or households, and the CCPA was supplemented by the California Consumer Rights Act (“CPRA”).

There are a number of other states that have considered similar privacy proposals, with states like Virginia and Colorado enacting their own privacy laws.

In addition, California enacted the California Consumer Privacy Act (“CCPA”), which creates individual privacy rights for California consumers (as defined in the law) and places increased privacy and security obligations on entities handling personal data of consumers or households, and the CCPA was supplemented by the California Consumer Rights Act (“CPRA”).

There are a number of other states that have considered similar privacy proposals, with states like Virginia and Colorado, among others, enacting their own privacy laws.

Some states are also considering consumer health data privacy laws, with states like Washington and Nevada enacting such laws.

In addition, the use of pixels and other website technologies increasingly are attracting attention from privacy regulators and private litigants, including under theories involving state wiretap laws.

These privacy laws may impact our business activities and exemplify the vulnerability of our business to the evolving regulatory environment related to personal data.

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The disaster recovery and business continuity plans we have in place currently may prove inadequate in the event of a natural disaster or similar event.

may incur substantial expenses as a result of any natural disaster, which could have a material adverse effect on our business.

We may incur substantial expenses as a result of any natural disaster, which could have a material adverse effect on our business.

We are subject to anti-corruption and a variety of other laws governing our international operations.

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Risks Related to Our Intellectual Property

Our ability to successfully commercialize our products may be impaired if we are unable to obtain and maintain effective intellectual property rights for our proprietary scientific technology platform and product candidates.

Our ability to successfully commercialize Symvess or our product candidates, if approved, may be impaired if we are unable to obtain and maintain effective intellectual property rights for our proprietary scientific technology platform, Symvess and our product candidates.

Our success depends in large part on our and our licensors’ ability to obtain and maintain patent and other intellectual property protection in the United States and in other countries with respect to our proprietary scientific technology platform and products.

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As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours or otherwise provide us with a competitive advantage.

The patent protection we obtain for our product candidates may not be sufficient enough to provide us with any competitive advantage or our owned or licensed patents may be challenged.

The patent protection we obtain for Symvess or our product candidates may not be sufficient enough to provide us with any competitive advantage or our owned or licensed patents may be challenged.

In some instances, agreements through which we license patent rights may not give us control over patent prosecution or maintenance, so that we may not be able to control which claims or arguments are presented, how claims are amended, and may not be able to secure, maintain, or successfully enforce necessary or desirable patent protection from those patent rights.

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Pending patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues from such applications.

Assuming the other requirements for patentability are met, currently, the first to file a patent application is generally entitled to the patent.

However, prior to March 16, 2013, in the United States, the first to invent was entitled to the patent.

For applications filed on or after March 16, 2013 in the United States, the first to file a patent application is generally entitled to the patent, assuming the other requirements for patentability are met.

Prior to March 16, 2013, however, the first to invent was entitled to the patent.

Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are not published until 18 months after filing, or in some cases not at all.

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Alternately or additionally, we may become involved in post-grant review procedures, oppositions, derivation proceedings, ex parte reexaminations, inter partes review, supplemental examinations, or interference proceedings or challenges in district court, in the United States or in various foreign patent offices, including both national and regional, challenging patents or patent applications in which we have rights, including patents on which we rely to protect our business.

An adverse determination in any such challenges may result in loss of the patent or in patent or patent application claims being narrowed, invalidated or held unenforceable, in whole or in part, or in denial of the patent application or loss or reduction in the scope of one or more claims of the patent or patent application, any of which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products.

stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products.

In addition, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.

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In addition, in any such proceeding or litigation, we could be found liable for monetary damages, which could be significant, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent.

A finding of infringement, misappropriation or that we otherwise violated intellectual property rights could prevent us from commercializing our product candidates or force us to cease some or all of our business operations.

A finding of infringement, misappropriation or that we otherwise violated intellectual property rights could prevent us from commercializing Symvess or our product candidates or force us to cease some or all of our business operations.

If we fail to comply with our obligations in our intellectual property licenses with third parties, we could lose license rights that are important to our business.

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• our right to sublicense patent and other rights to third parties under collaborative development relationships;

• whether we are complying with our obligations with respect to the use of the licensed technology in relation to our development and commercialization of product candidates;

• whether we are complying with our obligations with respect to the use of the licensed technology in relation to our development and commercialization of Symvess and our product candidates;

• our involvement in the prosecution of the licensed patents and our licensors’ overall patent enforcement strategy;

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The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology, or increase what we believe to be our financial or other obligations under the relevant agreement.

If disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangements on acceptable terms, or are insufficient to provide us the necessary rights to use the intellectual property, we may be unable to successfully develop and commercialize the affected product candidates.

If we or any such licensors fail to adequately protect this intellectual property, our ability to commercialize our products could suffer.

If we or any such licensors fail to adequately protect this intellectual property, our ability to commercialize Symvess or our product candidates, if approved, could suffer.

Any disputes with our licensors or any termination of the licenses on which we depend could have a material adverse effect on our business, financial condition, results of operations and prospects.

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Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

Patent terms may be inadequate to protect our competitive position on our HAVs or our other product candidates for an adequate amount of time.

Patent terms may be inadequate to protect our competitive position on Symvess or our product candidates for an adequate amount of time.

Patents have a limited lifespan.

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Various extensions may be available, but the life of a patent, and the protection it affords, is limited.

Even if patents covering our HAVs are obtained, once the patent life has expired, we may face competition, including from other competing technologies.

Even if patents covering our ATEVs, including Symvess, are obtained, once the patent life has expired, we may face competition, including from other competing technologies.

As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

We may not be able to protect our intellectual property rights throughout the world.

Filing, prosecuting, maintaining, defending and enforcing patents on our product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.

Filing, prosecuting, maintaining, defending and enforcing patents on Symvess or our product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States.

In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States.

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Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.

The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets, and other intellectual property protection, particularly those relating to biotechnology products, which could make it difficult for us to stop the infringement of our owned or licensed patents or marketing of

competing products in violation of our proprietary rights generally.

Proceedings to enforce our patent rights in foreign jurisdictions, whether or not successful, could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our owned or licensed patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us.

We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded to us, if any, may not be commercially meaningful.

In Europe, a new unitary patent system took effect on June 1, 2023, and may significantly impact European patents, including those granted before the introduction of the new system.

Under the new system, Applicants can, upon grant of a patent, opt for that patent to become a Unitary Patent which will be subject to the jurisdiction of a new Unitary Patent Court (“UPC”).

Patents granted before the implementation of the new system can be opted out of UPC jurisdiction, remaining as national patents in the UPC countries.

Patents that remain under the jurisdiction of the UPC may be challenged in a single UPC-based revocation proceeding that, if successful, could invalidate the patent in all countries who are signatories to the UPC.

Further, because the UPC is a new court system and there is little precedent for the court’s laws, there is increased uncertainty regarding the outcome of any patent litigation.

We are unable to predict what impact the new patent regime may have on our ability to exclude competitors in the European market.

In addition to changes in patents laws, geopolitical dynamics, including Russia’s incursion into Ukraine, may impact our ability to obtain and enforce patents in particular jurisdictions.

If we are unable to obtain and enforce patents as needed in particular markets, our ability to exclude competitors in those markets may be reduced.

Many countries have compulsory licensing laws under which a patent owner may be compelled under specified circumstances to grant licenses to third parties.

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The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations and may not adequately protect our business or permit us to maintain our competitive advantage.

• others may be able to make products that are similar to any product candidates we may develop or utilize similar technology but that are not covered by the claims of the patents that we own or license or may own or license in the future;

• others may be able to make products that are similar to Symvess or any of our product candidates we may develop or utilize similar technology but that are not covered by the claims of the patents that we own or license or may own or license in the future;

• we, or our current or future licensors might not have been the first to make the inventions covered by the issued patent or pending patent application that we own or license or may own or license in the future;

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As of December 31, 2024, we had 220 employees.

As we move forward in our efforts to commercialize our HAVs, if approved, we expect to continue to experience significant growth in the number of our employees and the scope of our operations, particularly in the areas of development, regulatory affairs, manufacturing, sales and marketing and quality and compliance and support functions.

As we move forward in our efforts to commercialize Symvess and our product candidates, if approved, we expect to continue to experience significant growth in the number of our employees and the scope of our operations, particularly in the areas of development, regulatory affairs, manufacturing, sales and marketing and quality and compliance and support functions.

Due to our limited financial resources, we may not be able to effectively manage the expansion of our operations, maintain competitive compensation packages, or recruit and train additional qualified personnel.

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• market prices and conditions in the industry in which we operate;

• publication of negative news articles or other media releases which could affect public opinion about our products or result in increased regulatory scrutiny of our product and product candidates;

• changes in government regulation;

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As of December 31, 2024, we had warrants outstanding to purchase up to an aggregate of 14,079,314 shares of our common stock and options outstanding to purchase up to an aggregate of 12,274,139 shares of our common stock.

As of December 31, 2024, we had the Option outstanding to purchase up to $8,050,000 worth of shares of our common stock.

Under the Humacyte, Inc.

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2021 Employee Stock Purchase Plan (the “ESPP”), as of December 31, 2024 we also have the ability to issue 5,817,353 shares and 1,030,033 shares, respectively.

In addition, the aggregate number of shares under the 2021 Plan and the ESPP will automatically increase on January 1 of each year commencing January 1, 2022, in an amount equal to 5% and 1%, respectively, of the number of shares of our capital stock outstanding on December 31 of the preceding year, unless our board of directors (the “Board”) acts prior to January 1 of a given year to provide that the increase for such year will be a lesser number.

As of December 31, 2023, we had the Option outstanding to purchase up to $10 million worth of shares of our common stock.

We may also issue additional shares of common stock or other equity securities of equal or senior rank in the future in connection with, among other things, future acquisitions or repayment of outstanding indebtedness, without stockholder approval, in a number of circumstances.

In addition, the aggregate number of shares under the 2021 Plan and the ESPP will automatically increase on January 1 of each year, in an amount equal to 5% and 1%, respectively, of the number of shares of our capital stock outstanding on December 31 of the preceding year, unless our board of directors (the “Board”) acts prior to January 1 of a given year to provide that the increase for such year will be a lesser number.

We may also issue additional shares of

common stock or other equity securities of equal or senior rank in the future in connection with, among other things, future acquisitions or repayment of outstanding indebtedness, without stockholder approval, in a number of circumstances.

Our issuance of additional shares of common stock or other equity securities of equal or senior rank would have the following effects:

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Any decision to declare and pay dividends as a public company in the future will be made at the discretion of the Board and will depend on, among other things, our results of operations, financial condition, cash requirements, contractual restrictions and other factors that the Board may deem relevant.

In addition, our ability to pay dividends may be limited by covenants of any existing and future outstanding indebtedness we or our subsidiaries incur.

In addition, our ability to pay dividends may be limited by covenants on any existing and future outstanding indebtedness we or our subsidiaries incur.

As a result, you may not receive any return on an investment in our securities unless you sell your securities for a price greater than that which you paid for it.

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If the Private Placement Warrants are held by holders other than the Sponsor, the underwriters or their permitted transferees, the Private Placement Warrants will be redeemable by us.

We have derivative securities that are accounted for as liabilities and the changes in value of such derivative securities could have a material effect on our financial results.

Included on the Company’s consolidated balance sheets as of December 31, 2023 are derivative liabilities related to the Contingent Consideration, the Private Placement Warrants, and the Purchasers’ put option under the Purchase Agreement.

We have derivative securities that are accounted for as assets and liabilities and the changes in value of such derivative securities could have a material effect on our financial results.

Included on the Company’s consolidated balance sheets as of December 31, 2024 are derivative liabilities related to the Contingent Consideration, the Private Placement Warrants, warrants issued in our October 2024 and November 2024 registered direct offerings (the “Registered Direct Offerings”), and the Purchasers’ put option under the Purchase Agreement, and a derivative asset related to our Common Stock Purchase Agreement.

Accounting Standards Codification 815, Derivatives and Hedging (“ASC 815”), provides for the remeasurement of the fair value of such derivatives at each balance sheet date, with a resulting non-cash gain or loss related to the change in the fair value being recognized in earnings in the statement of operations.

As a result of the recurring fair value measurement, our financial statements and results of operations may fluctuate quarterly, based on factors which are outside of our control.

Due to the recurring fair value measurement, we expect that we will recognize non-cash gains or losses on the Contingent Consideration and the Private Placement Warrants each reporting period and that the amount of such gains or losses could be material.

Due to the recurring fair value measurement, we expect that we will recognize non-cash gains or losses on the Contingent Consideration, the Private Placement Warrants and the warrants issued in our Registered Direct Offerings each reporting period and that the amount of such gains or losses could be material.

Our business could be adversely impacted by inflation.

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Inflation may also result in higher interest rates, which in turn would result in higher interest expense related to our variable rate indebtedness and any borrowings we undertake to refinance existing fixed rate indebtedness.

We are and may continue to be subject to legal and other proceedings that could cause us to incur significant expenses, divert our management’s attention, and materially harm our business, financial condition, and operating results.

As disclosed in Legal Proceedings , we and our affiliates currently are subject to various lawsuits and demands.

These proceedings, as well as any litigation, government inquiries or investigations, regulatory proceedings, as well as personal injury or class action claims and lawsuits, and securities, commercial and intellectual property infringement matters that we could face in the future, can be protracted and expensive, and have results that are difficult to predict.

Determining reserves for pending litigation and other legal and regulatory matters requires significant judgment, and there can be no assurance that our expectations or estimates will prove correct.

Adverse outcomes with respect to any of these legal proceedings may result in significant settlement costs or judgments, penalties and fines.

Even if these proceedings are resolved in our favor, the time and resources necessary to resolve them, or public scrutiny related to them, could divert the resources of our management and require significant expenditures.

Changes in U.S.

government policies under the Trump administration, including increased tariffs and reductions in federal research funding, could adversely affect our business.

Recent policy actions by the Trump administration, including the imposition of new tariffs on imported materials and goods from certain foreign countries, including Canada, Mexico and China, and the temporary freeze on federal grants and loans, may have an adverse impact on our business.

Increased tariffs on critical raw materials, components, and finished goods could raise our production costs, disrupt our supply chain, and reduce our competitiveness in the marketplace.

Additionally, the administration's halt on certain federal research grants may negatively impact our industry.

Any prolonged reductions in such funding could slow innovation, delay collaborations, and limit the adoption of new technologies that contribute to our business growth.

If these or similar policy changes continue or expand, we may face increased costs.

Although we cannot predict the full extent of these impacts, any prolonged disruption could adversely affect our business, financial condition, and results of operations.

We may be required to take write-downs or write-offs, restructuring and impairment or other charges that could have a significant negative effect on our financial condition, results of operations and stock price, which could cause you to lose some or all of your investment.

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These rules and regulations result in our incurring substantial legal and financial compliance costs and will make some activities more time-consuming and costly.

For example, these rules and regulations have made it more difficult and more expensive for Humacyte to obtain director and officer liability insurance, and it has accepted reduced coverage.

For example, these rules and regulations, and other factors, may make it more difficult and more expensive in the future for Humacyte to obtain director and officer liability insurance.

As a result, it may be difficult for us to attract and retain qualified people to serve on the Board or committees of the Board or as executive officers.

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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 1A. Risk Factors