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For the ATEV, we believe there is substantial clinical demand for safe and effective vascular conduits to replace and repair blood vessels throughout the body. Vascular injuries resulting from trauma are common in civilian and military populations, frequently resulting in the loss of either life or limb. Existing treatment options in the vascular repair, reconstruction and replacement market include the use of autologous vessels and synthetic grafts, which we believe suffer from significant limitations. For example, the use of autologous veins to repair traumatic vascular injuries can lead to significant morbidity associated with the surgical wounds created for vein harvest and prolonged times to restore blood flow to injured limbs, leading to an increased risk of complications such as amputation and reperfusion injury. In addition, in many instances of vascular trauma the patient may not have adequate vein available, or the time between injury and treatment is too long to make autologous graft repair feasible. Synthetic grafts are often contraindicated in the setting of vascular trauma due to wound contamination that contributes to higher infection risk that can lead to prolonged hospitalization and limb loss. Given the competitive advantages our ATEVs are designed to have over existing vascular substitutes, we believe that ATEVs have the potential to become the standard of care and lead to improved patient outcomes and lower healthcare costs.

As of December 31, 2025, our ATEVs have been implanted in approximately 636 patients in clinical trials as well as additional patients following the U.S. commercial launch of Symvess in the vascular trauma indication. In addition to vascular trauma, we are currently conducting a Phase 3 trial of our 6 millimeter ATEV in AV access for hemodialysis, and previously completed Phase 2 trials in PAD. We were granted Fast Track designation by the FDA for our 6 millimeter ATEV for use in AV access for hemodialysis in 2014. We also received the first Regenerative Medicine Advanced Therapy (“RMAT”) designation from the FDA, for the creation of vascular access for performing hemodialysis, in March 2017. In May 2023, we were granted the RMAT designation for the ATEV for urgent arterial repair following extremity vascular trauma, and in June 2024, we were granted the RMAT designation for the ATEV for patients with advanced PAD. In addition, in 2018 our ATEV product candidate was assigned a priority designation by the Secretary of Defense under Public Law 115-92, enacted to expedite the FDA’s review

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of products that are intended to diagnose, treat or prevent serious or life-threatening conditions facing American military personnel. We received our first FDA approval of the ATEV on December 19, 2024, a full approval for Symvess (acellular tissue engineered vessel-tyod) for use in 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.

In April 2023, we announced completion of enrollment of our V007 Phase 3 trial of the ATEV for use in AV access for hemodialysis. In July 2024, we announced positive topline results from our V007 Phase 3 trial, where the ATEV met the co-primary endpoints in the study. Dependent upon interim results from our ongoing V012 Phase 3 trial of the ATEV for use in AV access for hemodialysis in women, we plan to submit a supplemental BLA for the ATEV to the FDA for an indication in AV access for hemodialysis in the second half of 2026.

We have developed a novel paradigm for manufacturing human tissues that is intended to mimic key aspects of human physiology. We have an 83,000 square foot bioprocessing facility housing our modular manufacturing process with the ability to manufacture ATEVs of different diameters and lengths at commercial scale. As we continue to expand production, we believe we will have the ability to take advantage of economies of scale to reduce costs of production. We believe our established, controlled manufacturing process demonstrates a significant competitive advantage in the regenerative medicine market.

Our technology is protected by our patent portfolio, which includes certain patents licensed from parties as well as intellectual property generated internally at Humacyte. Our patent portfolio is comprised of 15 families of patents, many of which generally relate to the scaffolds used to make Symvess and our product candidates, the composition of Symvess and our product candidates and systems and methods of manufacturing Symvess and our product candidates. For more information, see “— Intellectual Property” below.

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

Our world-class senior management team and board of directors will be instrumental in helping us achieve our goals. Our President and Chief Executive Officer, Laura Niklason M.D., PhD., who founded Legacy Humacyte (as defined below), is an internationally respected physician scientist and a world leader in regenerative medicine technologies. Dr. Niklason is also a member of three national academies — Inventors, Medicine and Engineering. Our current Chair of the Board is Kathleen Sebelius, the former Secretary of the Department of Health and Human Services (“HHS”), and the former Governor of Kansas.

Merger

On August 26, 2021 (the “Closing Date”), Humacyte, Inc. (“Legacy Humacyte”) and Alpha Healthcare Acquisition Corp. (“AHAC”), consummated a merger pursuant to that certain Business Combination Agreement, dated as of February 17, 2021 (the “Merger Agreement”), by and among Legacy Humacyte, AHAC and Hunter Merger Sub (“Merger Sub”), a wholly owned subsidiary of AHAC. As contemplated by the Merger Agreement, Merger Sub merged with and into Legacy Humacyte, with Legacy Humacyte continuing as the surviving corporation and as a wholly owned subsidiary of AHAC (the “Merger” and collectively with the other transactions described in the Merger Agreement, the “Reverse Recapitalization”). On the Closing Date, AHAC changed its name to Humacyte, Inc. and Legacy Humacyte changed its name to Humacyte Global, Inc.

Unless the context indicates otherwise, references in this Annual Report on Form 10-K to the “Company,” “Humacyte,” “we,” “us,” “our” and similar terms refer to Humacyte, Inc. (formerly known as Alpha Healthcare Acquisition Corp.) and its consolidated subsidiaries (including Humacyte Global, Inc.) following the Merger. References to “AHAC” refer to Alpha Healthcare Acquisition Corp. prior to the Merger.

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Our Approach

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

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

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

Over time, we intend to develop a readily available “cabinet” of ATEVs of varying diameters and lengths to address the significant unmet needs across multiple potential indications in vascular repair, reconstruction and replacement.

Our Proprietary Scientific Technology Platform

Our proprietary scientific technology platform uses primary human aortic vascular cells from a working cell stock that have been isolated from donor tissues and cryopreserved. The working cell stock is expanded using traditional cell culture techniques, and the cells are transferred onto a biocompatible, biodegradable polymer mesh within a flexible, single-use bioreactor bag. Over the course of weeks, the cells proliferate and build extracellular matrix while the polymer mesh degrades. The resulting bioengineered vessel is comprised of the aortic vascular cells and their deposited extracellular matrix. After completion of the culture period, we decellularize the bioengineered vessel using a proprietary combination of solutions. The resulting ATEV retains the extracellular matrix constituents and, therefore, the biomechanical properties of the bioengineered vessel, but is cleansed of the cells and cellular components that could induce a foreign body response or immune rejection following implantation. Our functionally closed system allows for the ATEV to be grown, decellularized and ultimately shipped within the same flexible bioreactor bag. Our ATEVs are designed to be shipped to hospitals, trauma centers and outpatient surgical settings, where they can then be refrigerated for immediate use by removing each ATEV from its packaging.

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

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Our Novel Manufacturing Paradigm

We have developed a novel paradigm for manufacturing human tissues that is intended to mimic key aspects of human physiology. Our proprietary manufacturing process was designed with a modular approach allowing us to produce ATEVs in smaller batches for clinical trials and scale out to larger batches for commercial manufacturing. In 2021 we commenced supplying our ongoing clinical trials with ATEVs produced in our current, commercial-scale LUNA200TM system, which consists of 20 growth drawers per production unit for a total of 200 ATEVs per batch. Each growth drawer is capable of producing ten 42cm ATEVs, each of which is contained within an individual bioreactor bag. Inside a LUNA200, a tubing network connects all ATEVs, allowing the entire system to share nutritive media. In this way, a single LUNA200 can produce up to 200 ATEVs (42cm in length) per batch while maintaining the critical operating parameters, such as biomechanical pulsing, that affect growth. The FDA inspected our manufacturing facility in April 2024 as part of its review and approval of our BLA in extremity vascular trauma, and we are using this facility to provide product for the United States commercial launch in that indication which commenced in the first quarter of 2025.

Our current 83,000 square foot manufacturing facility has space to further expand manufacturing capacity as needed to over 40 LUNA200 systems. Currently, eight LUNA200 systems are installed and operational.

We believe that the LUNA200 can produce ATEVs in diameter sizes from 3mm to 10mm and lengths from 10cm to 42cm, making the equipment suitable for the varied array of product candidates in our pipeline. We currently intend to introduce a 13cm-long ATEV line extension after the commercial launch of the 42cm ATEV, for surgeries that require shorter segments of ATEV in the setting of vascular trauma and repair. Using our existing LUNA200 manufacturing equipment without modification, we believe we have the ability to generate 400 ATEVs (13cm in length) or 200 ATEVs (42cm in length) per manufactured batch. We have designed our manufacturing system to be functionally closed, to utilize single-use disposable materials with aseptic connections, and to be highly automated, which allows us to control and maximize ATEV production.

Based on observations to date, the ATEV has withstood maximal pressures that are comparable to those reported for native arteries. For example, the human aorta is reported to have rupture strengths around 1,400 mmHg, while human cerebral arteries rupture around 1,800 mmHg. We have observed ATEVs withstanding maximal pressures of approximately 3,200 mmHg before rupturing, making their mechanical properties on par with native human blood vessels.

Our Market Opportunity

We are a biotechnology company that has commenced the U.S. commercial launch of one FDA-approved product, with Phase 3 clinical trials in two indications and a strong pipeline for additional products and indications. Additionally, we have had significant interest from surgeons to use our ATEV in life and limb saving surgeries as demonstrated by their requests to the FDA to use our ATEV in multiple expanded access (compassionate use) cases where no alternative was available, as well as requests from Ukrainian surgeons that led to a humanitarian program conducted during the conflict in that country.

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Our Initial Market Opportunity in Vascular Repair, Reconstruction and Replacement

We believe there is a significant market opportunity for our technology across a number of important clinical areas within vascular reconstruction and replacement including vascular trauma, AV access for hemodialysis, PAD, and adult cardiac surgery. To treat these diseases and conditions, patients often require invasive vascular and cardiovascular surgery, which involves the use of alternative vascular synthetic materials or autologous vessels harvested from elsewhere in the body. For more information about our evaluation of market opportunity, see “Risk Factors — Risks Related to the Development and Commercialization of Our Product Candidates — The sizes of the market opportunities for our product candidates have not been established with precision and are estimates that management believes to be reasonable. If these market opportunities are smaller than we estimate or if any approval that we obtain is based on a narrower definition of the relevant patient population, our revenue and ability to achieve profitability might be materially and adversely affected.”

Vascular Trauma: Arterial injuries resulting from vascular trauma are common in military and civilian populations, frequently resulting in the loss of life or limb. In military populations, as the rate of battlefield fatalities has been declining due to faster evacuations and more robust protection from body armor, the rate of survivable vascular injuries has been increasing. In civilian populations, trauma injuries are primarily caused by motor vehicle, workplace and sporting accidents, gun violence, mass casualty terrorist attacks, stabbings, blunt trauma, and iatrogenic injuries (injuries caused by medical treatment or examination). We estimate that central or peripheral vascular injuries in civilian patients account for approximately 150,000 of all injuries reported in global trauma patients. Furthermore, these injuries account for greater than 20% of all trauma-related deaths.

Civilian patients with central or peripheral vascular injuries are estimated to account for approximately 80,000 of all injuries reported in trauma patients in the United States, inclusive of urgent and iatrogenic vascular trauma injuries, and account for greater than 20% of all trauma-related deaths. Based on an analysis of the Definitive Healthcare Claims (DHC) Database 2023, we estimate that approximately 26,000 patients per year will be eligible for the ATEV within the United States (analysis was based on inclusion of patients with major repairs to injuries of the extremities, and the exclusion of patients with vein injuries, injuries to the torso, head, neck, wrist, hand, ankle or foot, or who received ligation or endovascular repair).

We believe our ATEVs are a promising alternative that can address critical gaps in existing treatment options for acute vascular injuries due to trauma. We have developed our ATEVs with the goal of providing an effective solution in all time-constrained surgical environments and in resource-limited, infection prone civilian and battlefield conditions. The ability to provide immediately available, non-immunogenic, universally implantable human vessels that have low rates of infection represents a clinically significant advantage over existing treatment options. In addition, the Budget Impact Model for the ATEV,

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published in the Journal of Medical Economics in March 2025, reported that the ATEV was projected to be cost saving for both trauma centers and third-party payors, primarily due to reductions in the costs related to amputations and conduit infections.

AV Access for Hemodialysis: An estimated $5 to $6 billion per year is spent on hospital admissions in hemodialysis patients with infection and access complications. In 2024, over 555,000 patients received hemodialysis in the United States. Annually, at least 160,000 existing or new dialysis patients require a new AV access in the U.S. and an additional 150,000 patients require a new AV access in Europe and Japan.

Hemodialysis patients are a chronically ill population, suffering an average of 1.8 hospital admissions, three visits to the emergency department, and four days hospitalized for infections each year. The two most common causes of hospital admissions in hemodialysis patients are infection and access complications. For hemodialysis patients, an infected access site can lead to sepsis, a life-threatening complication that is the most expensive cause for hospitalization in the United States and carries at least a 10% overall mortality rate.

We believe that our ATEVs, when used as AV access for hemodialysis, can decrease infections and dialysis access failures, which would improve patient outcomes and lower the burden of dialysis costs on the healthcare system. Subject to the outcome of the interim data analysis of the V012 clinical trial, we expect to file a BLA with the FDA in the second half of 2026 seeking approval for the use of ATEV in AV access for hemodialysis, and to target our commercialization efforts particularly toward those patients who are at high risk of fistula failure or non-maturation, such as women and male patients with two risk factors, such as obesity and diabetes.

Peripheral Artery Disease: PAD is a cardiovascular disease of blood vessels located outside the brain and heart. Atherosclerosis, which is the buildup of plaque along the artery walls, usually affects arteries in the legs, but it can also affect arteries that carry blood from the heart to the head, arms, kidneys, and intestines. We believe our ATEVs can be used as a bypass conduit in patients suffering from PAD in the legs. Peripheral arterial bypass procedures are common with over 230,000 PAD-related procedures reported annually in the U.S. There are over 200,000 peripheral bypass procedures per year in Europe, and approximately 220,000 per year in Asia.

While endovascular techniques have become more available over the past ten years to treat an array of vascular occlusions, depending on the nature and length of the blockage these types of treatment options have had limited success and durability as compared to conventional surgical bypass. Both angioplasty and stenting procedures provide near term success, however long-term durability has remained a question, as highlighted in the results of the recent BEST-CLI clinical trial published in the New England Journal of Medicine demonstrating that patients treated with surgical bypass had fewer major amputations and less need for repeat procedures than those treated with endovascular therapy.

Type I Diabetes: Type 1 diabetes, caused by auto-immune destruction of insulin-producing cells in the islets of the pancreas, is a devastating disease affecting more than 1.5 million people in the United States, and costing at least $10 billion to $14 billion annually. In Europe and Asia, the number of patients suffering with Type 1 diabetes is estimated at approximately 2.8 million and 2.0 million, respectively. Even with the newer insulin delivery technologies, less than one-third of patients achieve consistent target blood sugar levels.

Pancreas transplantation is limited due to the associated morbidity and cost of a whole pancreas organ transplantation procedure. As an alternative to pancreas transplantation, the “Edmonton Protocol” has been developed whereby insulin producing cells are transplanted into the portal vein in the liver. However, the majority of the injected cells are lost to inflammation and clotting, and only 16% of Type 1 diabetes patients who receive the Protocol are cured long term.

We believe our ATEVs present a means to deliver a therapeutic number of pancreatic islets to patients with Type 1 diabetes. Pancreatic islets are embedded on the outer surface of our ATEV and may be implanted as an AV graft, analogous to the outpatient procedure done for hemodialysis access. After implantation, the islets may have the potential to sense blood glucose and then respond by secreting appropriate levels of insulin to maintain proper glucose levels in the blood. We have termed this new paradigm for pancreatic islet cell delivery the BioVascular Pancreas or “BVPTM.”

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We believe that a reliable, low-risk, and easily implantable islet cell delivery method that could ensure the survival and functionality of a therapeutic number of islet cells in a human adult would be transformational for the treatment of Type 1 diabetes.

Coronary Artery Bypass Graft: CABG is a surgery used to treat a blockage or narrowing of one or more of the coronary arteries to restore the blood supply to the heart muscle. We believe our ATEVs can replace existing vascular substitutes and improve patient outcomes, particularly in obese patients or those suffering from diabetes, in whom the risks of saphenous vein harvesting are more substantial. CABG procedures are common, with more than 400,000 CABG procedures reported annually in the U.S. and over 800,000 annual CABG procedures globally.

Typically, a CABG operation involves the use of both the patient’s own artery and vein. In patients who are obese, have diabetes, or who are very elderly, there are higher risks for vein harvest complications, including failure to heal the vein harvest incision, infection, and prolonged swelling of the operative leg. Furthermore, complications from the vein harvest incision site are more common than complications from the chest incision in CABG patients. It is estimated that approximately 20% of patients requiring bypass surgery have no suitable grafts available, with sources reporting as high as 45% of CABG patients are without suitable autologous vein. In preclinical testing, we have evaluated a small diameter ATEV (“sdATEV”) which is 3.5mm in diameter and 20cm in length for use as a CABG conduit. Testing has been performed in non-human primates, pigs and sheep. We plan to utilize the collective preclinical data on the sdATEV to support an Investigational New Drug (“IND”) application to the FDA for CABG during 2025.

Pediatric Heart Surgery: We have evaluated in preclinical testing a smaller diameter ATEV product for use in pediatric heart surgery as a Blalock Taussig (“BT”) shunt. The BT shunt is a surgical procedure that is used to increase pulmonary blood flow for the treatment of babies born with a complex congenital heart defect called Tetralogy of Fallot, a common type of “blue baby syndrome”. There are approximately 1,800 babies born in the United States with Tetralogy of Fallot each year. The BT shunt is a life-saving procedure for these babies, and we plan to submit an orphan drug application for use of our ATEV as a BT shunt for infants born with cyanotic congenital heart defects. Although 3 – 4mm inner diameter expanded polytetrafluoroethylene (“ePTFE”) grafts are currently used as the most common BT shunt, they suffer from limitations that impact morbidity and mortality in these infants.

Our Product Pipeline

The following table highlights key information about the most active programs within our current product pipeline:

We began clinical evaluations of our ATEVs in December 2012, with the enrollment of the first Phase 2 patient in our V001 hemodialysis access trial in Europe. Since then, we have completed two pivotal and one Phase 2 trials in the United States, and currently have one pivotal trial actively enrolling and two trials in long-term follow-up. In clinical trials and in expanded access cases, ATEVs have been implanted in approximately 85 clinical centers in seven countries around the world, and by more than 100 practicing surgeons.

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Overview of Clinical Trials Assessing the Safety and Efficacy of the ATEV in Multiple Indications

Clinical Trial

Number

Indication

Begin

Enrollment

Design/Phase

Number of

Subjects

Status

Outcomes**

Vascular Trauma

V005

Vascular Trauma

2018

Phase 2/3 Single-arm Historical Comparator Unblinded

72 total. Primary analysis based on a total of 51 patients with injuries of extremities

BLA approved by FDA December 19, 2024

30-day PP: 84.3%

30-day SP: 90.2%

Infection Rate: 2.0%

Amputation Rate: 9.8%

V017

Vascular Trauma

2022

Retrospective observational study to evaluate the ATEV in real-world setting of humanitarian program conducted during wartime in Ukraine

19 total treated under humanitarian program. 17 consented for inclusion in study, 16 of whom had injuries of extremities and were included in primary analysis

Included in BLA submission approved by FDA December 19, 2024

30-day PP: 93.8%

30-day SP: 93.8%

Infection Rate: 0%

Amputation Rate: 0%

Dialysis Access

V001

Dialysis Access

2012

Phase 2 Single-arm

40

Completed

30-day PP: 95%

6-month SP: 100%

12-month SP: 97%

60-month SP: 58%

Infection Rate/yr: 0%

Number of Rejections: 0

V003

Dialysis Access

2013

Phase 2 Single-arm

20

Completed

30-day PP: 95%

6-month SP: 89%

12-month SP: 81%

Infection Rate/yr: 4% (1 event)

Number of Rejections: 0

V006

Dialysis Access

2016

Phase 3 Prospective Randomized Blinded

355 total; 177 received ATEV, 178 received ePTFE

Completed

30-day PP ATEV: 93%

12-month SP ATEV: 82%

24-month SP ATEV: 67%

12-month SP ePTFE: 80%

24-month SP ePTFE: 74% Infection Rate ATEV/yr: 0.93%

Infection Rate ePTFE/yr: 4.5%

Number of ATEV Rejections: 0

V007

Dialysis Access

2017

Phase 3 Prospective Randomized Blinded

242 total; 123 received ATEV, 119 received AVF

Topline results reported August 2024, two-year follow-up in process

6-month SP ATEV: 81%

12-month SP ATEV: 68%

6-month SP AVF: 66%

12-month SP AVF: 62%

V011

Dialysis Access

2019

Phase 2 (LUNA200 Manufacturing System Bridging Study)

30

Completed

30-day PP: 97%

30-day SP: 100%

12-month SP: 83%

Infection Rate ATEV/yr: 0%

Number of ATEV Rejections: 0

V012

Dialysis Access

2023

Phase 3 Prospective Randomized Blinded

Target 150 women total, 113 currently enrolled

Enrollment ongoing

Trial is currently enrolling, interim analysis planned on first 80 patients after one-year of follow up. The 80th patient is expected to complete one year of follow up in April 2026.

Peripheral Artery Disease

V002

PAD

2013

Phase 2 Single-arm

20

10-year follow-up ongoing

30-day PP: 100%

6-month SP: 84%

12-month SP: 84%

72-month SP: 60%

Infection Rate/yr: 0%

Number of Rejections: 0

V004

PAD

2016

Phase 2 Single-arm

15

Completed

30-day PP: 100%

6-month SP: 86%

12-month SP: 64%

Infection Rate/yr: 0%

Number of Rejections: 0

Number of Amputations: 0

** PP: Primary Patency, which is the interval of time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis, or the time of measurement of patency, i.e. patent without interventions.

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SP: Secondary Patency, which is the interval from the time of access placement until abandonment, i.e. patent with or without interventions.

As of December 31, 2025, approximately 636 patients worldwide have received our ATEVs in clinical trials, and expanded access and humanitarian programs, for the treatment of vascular trauma, AV access for hemodialysis, PAD, and in expanded access cases resulting in approximately 1,363 subject-years of exposure to the ATEV, in each case excluding additional patients that have received our ATEVs following the U.S. commercial launch of Symvess in the vascular trauma indication. Our cumulative ATEV exposure in clinical trials is approximately 1,026 subject-years in the hemodialysis access population, 216 subject-years in the PAD population, and 121 subject-years in the arterial trauma population. The longest our ATEV has been in a patient and used for dialysis is more than ten years. A total of 30 expanded access/compassionate use cases have been granted by the FDA, and another 35 patients with severe PAD have been treated with the ATEV under an investigator IND at the Mayo Clinic. Lastly, 19 patients suffering vascular injuries during the conflict in Ukraine have been treated with the ATEV under a humanitarian program. Throughout all of these trials and other programs, we have observed that our ATEVs functioned as intended and provided functional blood flow to affected limbs. We have also observed consistent durability with a strong tolerability profile. Furthermore, we have observed no evidence of clinically relevant immunologic reactions to our ATEVs, supporting the potential use of our ATEVs as off-the-shelf, universally implantable, bioengineered human tissues.

Overall, the ATEV has functioned well and as intended, across ten different clinical trials in three clinical indications. As of December 31, 2025, the ATEV has been implanted in patients in clinical trials across more than 85 clinical sites in seven countries, over more than ten years. We have observed zero instances of clinical rejection of the ATEV in any clinical trial over the past ten years, suggesting that the ATEV was not immunologically rejected after implantation.

Based on clinical trial results to date, we have observed that the ATEVs have a low infection rate, with an infection rate averaging approximately 1.0% or less per patient-year in our AV access trials, and low infection rates in our trauma and PAD trials (ranging from 0% to approximately 2%, depending on the trial and indication). Vascular graft infections are a potentially serious complication and can result in adverse outcomes such as sepsis, hospitalization, long-term antibiotic use, repeat procedures and even death.

ATEVs Remodel with Host Cells After Implantation

Additionally, based on clinical samples obtained during our Phase 2 AV access trials and published in three peer reviewed journals, The Lancet in 2016, Science Translational Medicine in 2019, and in the Journal of Vascular Surgery in 2020, we observed that the ATEV became populated with healthy, vascular cells from the patient. As described in these publications, over time the patient’s cells have been observed to transform the ATEV into a multi-layered living tissue similar to native blood vessels. In these trials we have also observed ongoing cellular repair of ATEV tissues that had been previously injured during cannulation with dialysis needles, which suggests that the recellularized ATEV may be capable of self-healing. The image below shows an ATEV that had been implanted in a hemodialysis patient for 44 weeks, that had developed alpha-actin positive vascular smooth muscle cells throughout the wall (red staining in the left-hand panel), and had developed a layer of CD31+ endothelial cells on the inner luminal surface of the ATEV (line of red endothelial cells indicated in the right-hand panel).

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Histological Images of ATEV Repopulated with the Patient’s Own Vascular Cells

ATEVs Low Rate of Infection

In July 2023, a preclinical study that supported a possible scientific basis for the low rates of infection that have been observed in clinical trials of the ATEV was published in the Journal of Vascular Surgery – Vascular Science. This work compared the infection resistance of the ATEV to ePTFE grafts, which are made of plastic. The laboratory results suggest that the bioengineered human tissue of the ATEV may have superior compatibility with the body's own neutrophils (white blood cells that combat bacterial infections) as compared to ePTFE. Histology and laboratory analyses performed in the preclinical study suggests that while human white blood cells die when they come in contact with ePTFE, the cells survive and function in contact with the ATEV, which may improve the ability of the ATEV to fight dangerous infections once implanted in the body.

Indication #1: Use of ATEV to Repair Extremity Vascular Trauma

Overview of Vascular Trauma

Arterial injuries resulting from vascular trauma are common in military and civilian populations, frequently resulting in the loss of life or limb. In military populations, as the rate of battlefield fatalities has been declining due to faster evacuations and more robust protection from body armor, the rate of survivable vascular injuries has been increasing. In civilian populations, trauma injuries are primarily caused by motor vehicle, workplace and sporting accidents, gun violence, mass casualty terrorist attacks, stabbings, blunt trauma and iatrogenic injuries (injuries caused by medical treatment or examination). Consequently, we believe there is an increasingly urgent unmet need for novel materials that are immediately available for permanent vascular repair for both civilian and military vascular trauma.

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Options in Surgical Treatment of Vascular Trauma

Autologous vein is the preferred conduit for vascular repair. However, harvesting of autologous vein is not always feasible, due to damage to vein or lower limb, prior vein harvest, inadequate size of the vein or venous disease. Harvesting autologous vein is a serious operation that requires additional time and resources. Delaying the time from injury to operative intervention from less than one hour, to three hours or greater, more than doubles the risk of limb amputation. Limb amputation, in turn, almost triples the length of intensive care unit stay, nearly doubles the length of hospital stay, and is devastating to patient quality of life. Additionally, the morbidity associated with saphenous vein harvest includes surgical site infections, chronic pain, and limb swelling. Synthetic materials have been shown to be inferior to autologous vein in resistance to infection and durability and, therefore, are generally only used for vascular repair when autologous vein is not an option.

The ATEV as a Solution for Vascular Trauma

We believe our ATEVs are a promising alternative that can address critical gaps in existing treatment options for acute vascular injuries due to trauma. We have developed our ATEVs with the goal of providing an effective solution in all time-constrained surgical environments and in resource-limited, infection prone civilian and battlefield environments. The ability to create immediately available, non-immunogenic, universally implantable material that has a low infection rate represents a clinically significant advantage over existing options.

Humacyte has a strong working relationship with the Department of Defense (“DoD”) that has led to a partnership over the last decade to support their unmet need to reconstruct and repair vascular injuries through the development of our ATEVs. As a result of this collaboration and partnership with the DoD, we anticipate Humacyte would supply ATEVs for use in military hospitals to treat injured soldiers and veterans. The DoD assigned a priority designation to the ATEV technology under Public Law 115-92. Under this law, FDA and DoD work together to expedite the development and review of critical technologies and therapies requested by DoD. Additionally, we have received an approximately $6.8 million grant from the DoD for the development of our ATEVs for vascular reconstruction and repair.

FDA Approval of ATEV for Extremity Vascular Trauma

In May 2023, the FDA granted RMAT designation for use of the ATEV in urgent arterial repair following extremity vascular trauma. In December 2023, the Company filed a BLA with the FDA for urgent arterial repair following extremity vascular trauma when synthetic graft is not indicated, and autologous vein use is not feasible. The BLA submission was supported by results from the V005 Phase 2/3 clinical trial, and real-world outcomes from the treatment of wartime injuries in Ukraine, both of which are described below. On December 19, 2024, the FDA granted full approval for Symvess (acellular tissue engineered vessel-tyod) for use in 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.

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V005 Phase 2/3 Civilian Trial for Vascular Trauma

Trial Design: Our V005 civilian trial was a single-arm, multi-center, non-randomized clinical trial to evaluate the efficacy, safety and tolerability of our 6 millimeter ATEV in replacement or reconstruction of vascular tissues in patients with life or limb-threatening vascular trauma for whom the standard of care, saphenous vein, was not feasible or available for vascular repair. As a single-arm study, the comparators for the ATEV results were derived from a systematic literature review and meta-analysis of studies evaluating synthetic grafts in vascular injury repair. A total of 72 patients were enrolled in the V005 trial, of which 51 had vascular injury of the extremities and comprised the primary evaluation group for the study. The primary efficacy endpoint was patency of the ATEV at 30 days, with 30-day rates of infection and amputation comprising the secondary endpoints.

V005 Trial Results:

The results discussed below are for the subgroup of 51 V005 patients with extremity injury submitted with the BLA as the primary analysis subgroup. In this subset of V005 patients, the range of trauma injuries were broad, including penetrating trauma cases and blunt injury cases. Mechanisms of injury included motor vehicle accidents, gunshot wounds, industrial accidents, and falls in the V005 trial. The ATEVs were placed throughout the body, including in the lower limbs and upper limbs and were used to repair the axillary artery, femoral artery, popliteal artery and vein, and the brachial artery. Many of the injuries treated in the V005 trial were contaminated injuries that are at elevated risk of graft infection.

The most common reasons reported by clinicians for using the ATEV in the V005 trial instead of the standard of care, saphenous vein, was the need to avoid the time required to harvest saphenous vein (32.3%), the quality of the patient’s vein (25.8%), and concomitant injuries to the vein (16.1%), suggesting that the ready, off-the-shelf feature of the ATEV has the potential to save valuable time for surgeons in the restoration of blood flow.

The V005 trial met its objectives. V005 results included in the BLA submission to the FDA and published in JAMA Surgery, an American Medical Association peer-reviewed journal, in November 2024, are summarized in the following table.

V005 Phase 2/3 ATEV Results in Vascular Trauma Compared to Synthetic Graft Benchmark

30-Day Endpoint

V005 Trial

ATEV Extremity Group (n=51)

(%)

Synthetic Graft Benchmark (%)

Primary Patency

84.3%

78.9%

Secondary Patency

90.2%

78.9%

Conduit Infections

2.0%

8.4%

Amputations

9.8%

24.3%

In the package insert for Symvess, the FDA applied a different imputing methodology for V005 Symvess patients who did not have a day 30 assessment. For patients who missed day 30 follow-up due to unrelated death or loss of follow-up, patients were imputed as treatment failures (i.e., loss of patency, and failure of limb salvage). The FDA also added three more patients enrolled after data cutoff.

V005 Phase 2/3 ATEV Results in Vascular Trauma in Package Insert

30-Day Endpoint

V005 Trial

ATEV Extremity Group (n=54) (%)*

Primary Patency

66.7%

Secondary Patency

72.2%

Conduit Infections

1.9%

Limb Salvage

75.9%

_________________

* Nine patients not available for Day 30 assessment were imputed as failures for patency and limb salvage estimation.

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This imputing methodology used in the package insert was different than that used in the synthetic graft benchmark publications. The FDA elected to exclude the synthetic graft comparator from the package insert.

The safety profile of the ATEV in the V005 trial was consistent with previous studies and there were no cases of clinical rejection of the ATEV. A summary of adverse events (“AEs”) for the duration of the study (mean duration of follow up is 295 days) is included in the table below.

V005 Phase 2/3 ATEV Adverse Events

Adverse Event

V005 Trial - ATEV Extremity Group (n=51)

Number of Patients (%)

Total Adverse Events

50 (98.0%)

Non-Fatal Serious Adverse Events

28 (54.9%)

Deaths:

At Day 30

Over Duration of Study

3 (5.9%)

4 (7.8%)

ATEV Infections

2 (3.9%)

ATEV Rupture

1 (2.0%)

ATEV Occlusion/Thrombosis

15 (29.4%)

Pseudoaneurysm

1 (2.0%)

Aneurysm

1 (2.0%)

Other

2 (3.9%)

There were no unexpected safety signals for the ATEV in the V005 trial. The most common AEs were thrombosis, anemia, pyrexia, thrombocytopenia, constipation, nausea, peripheral edema, and tachycardia. The most common non-fatal Serious Adverse Events (“SAEs”) were thrombosis, anastomotic stenosis, wound infection, muscle necrosis, wound infection, hemorrhage shock, and cardiac arrest. Deaths occurring prior to day 30 were adjudicated as not casually related to the ATEV by an Independent Adjudication Committee.

In December 2025 long-term data assessing the durability of ATEV in patients followed from the V005 trial were published in the Journal of Vascular Surgery Cases, Innovations and Techniques (JVS-CIT). In the study, titled “Long-term Safety and Efficacy Outcomes of the Acellular Tissue Engineered Vessel (ATEV) in Extremity Arterial Trauma Repair,” the ATEV was observed to maintain structural integrity over the long term, exhibit low infection rates, and support high rates of limb salvage in patients followed for up to 36 months. Once early complications from the traumatic injuries resolved, the rates of conduit infection, limb salvage, and patient survival plateaued and remained relatively constant through the three years of follow-up. Symvess maintained an infection-free rate of 92.9% from months 3–36, with no infections after day 37 and only three conduit infections overall. Limb salvage rates were 87.3% at 12 months and 82.5% at 24 months, despite a severely injured trauma cohort. Adverse events and serious adverse events were also observed to decline over time, supporting the long-term durability of this vascular repair. Importantly, no deaths, amputations, or mechanical failures were attributed to Symvess. No spontaneous (i.e., unprovoked by external factors) ruptures or structural failures were reported in any patient throughout the follow-up period.

We believe the V005 trial results indicate that for patients in need of extremity arterial repair, when use of autologous vein was not suitable, and who were at high-risk level for wound infection, the ATEV may offer an effective option for revascularization. A case study from the trial is shown in the figure below, a photograph of an ATEV that was used to repair both an artery and a vein in the knee of a patient who suffered a gunshot wound. This patient was doing well at the 30-day follow-up visit with both repairs remaining patent and functional.

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Intra-operative photograph of ATEV repair of popliteal artery (left) and vein (right) in V005 subject.

Ukraine Humanitarian Program, - V017 Trial

V017 Background and Results:

In the second quarter of 2022, Humacyte launched a humanitarian initiative to provide its ATEVs to hospitals in Ukraine for the treatment of wounded civilians and soldiers with vascular trauma injuries. Ukrainian surgeons presented patient outcomes from the use of the ATEV to treat wartime vascular trauma at two vascular conferences in December 2022, the VI Congress of Vascular Surgeons, Phlebologists, and Angiologists of Ukraine in Kyiv, Ukraine, and the 11th Munich Vascular Conference (MAC) 2022. The surgeons described long-standing limitations in vascular tissue repair and replacement as well as the injuries that they have observed during the Russian-Ukrainian conflict. Surgeons utilized the ATEV to treat patients with wartime injuries including blast trauma, shrapnel injuries, and gunshot wounds. The surgeons observed that access to the ATEV, a biologic conduit, has improved their ability to perform vascular reconstructions by eliminating the need to harvest a venous conduit. A total of 19 vascular patients were treated under this humanitarian program, and results from 16 of these patients were published in JAMA Surgery in November 2024, along with results from the V005 trial.

The FDA advised Humacyte to include in the BLA submission patient outcomes from the Ukraine humanitarian program. We refer to the results for the 16 patients from Ukraine with extremity vascular trauma who provided consent for use of their results in the BLA filing as the V017 trial. A high success rate for the 16 extremity patients in the V017 trial was observed, despite the presence of contaminated wound beds, as summarized in the table below.

V017 Ukraine Humanitarian ATEV Results in Vascular Trauma

30-Day Endpoint

V017 Trial

ATEV Extremity Group (%)

Primary Patency

93.8%

Secondary Patency

93.8%

Conduit Infections

0.0%

Amputations

0.0%

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The safety profile of the ATEV in the V017 trial was consistent with previous studies and there were no cases of clinical rejection of the ATEV. A summary of AEs for the duration of the study (mean duration of follow up is 139 days) is included in the table below.

V017 Ukraine Humanitarian ATEV Adverse Events

Adverse Event

V017 Trial - ATEV Extremity Group (n=16)

Number of Patients (%)

Total Adverse Events

4 (25.0%)

Non-Fatal Serious Adverse Events

1 (6.3%)

Deaths:

At Day 30

Over Duration of Study

0 (0.0%)

0 (0.0%)

ATEV Infections

0 (0.0%)

ATEV Rupture*

1 (6.3%)

ATEV Occlusion/Thrombosis

1 (6.3%)

Pseudoaneurysm

0 (0.0%)

Aneurysm

0 (0.0%)

__________________

* One ATEV rupture associated with extensive shrapnel remnants in the wound that caused bleeding.

In the figure below, photographs are shown of the first patient treated under the humanitarian program in Ukraine. The patient was a 42-year-old male who suffered a gunshot wound in the leg which damaged his femoral artery. The patient was initially treated using synthetic graft which became infected, and the patient experienced critical right lower extremity ischemia. The ATEV was implanted as a right superficial femoral artery reconstruction to achieve wound healing and limb salvage. After three months, the ATEV was reported to have retained primary patency with no evidence of ATEV infection.

Intra-operative photographs of attempted synthetic graft repair of femoral artery (left) and subsequent repair with ATEV (right) in patient from Ukraine humanitarian program.

In September 2025 long-term results from the V017 trial were published in Oxford Academic’s Military Medicine. The publication, titled “Evaluating the Safety and Efficacy of Humacyte Acellular Tissue-Engineered Vessel in a Real-World Combat Setting: A Retrospective Observational Multicenter Study,” reported that patients from the V017 trial were observed to have a continued high rate of patency (87.1%), 100% limb salvage, and zero cases of conduit infection in 17 patients with arterial injury repairs followed for up to 18 months.

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Combined V005 and V017 Results of ATEV for Vascular Trauma

The BLA submission was supported by the combined results from the V005 (civilian) Phase 2/3 clinical trial and real-world outcomes from the treatment of wartime injuries in Ukraine in the V017 (military) trial. Combined results included in the BLA submission to the FDA and published in JAMA Surgery in November 2024 are summarized in the following table. The Synthetic Graft Benchmark publications included a combination of civilian and military injuries.

Combined V005 Phase 2/3 ATEV and V017 Ukraine Real-World Results in Vascular Trauma

Compared to Synthetic Graft Benchmark

Outcome Day 30

ATEV V005

(n=51)

ATEV V017

(n=16)

Combined ATEV (n=67)

Synthetic Graft

Benchmark

Primary Patency

84.3%

93.8%

87.1%

78.9%

Secondary Patency

90.2%

93.8%

91.5%

78.9%

Conduit Infection Rate

2.0%

0.0%

0.9%

8.4%

Amputation Rate

9.8%

0.0%

4.5%

24.3%

Death Rate (all causes)

5.9%

0.0%

3.5%

3.4%

The ATEV demonstrated a higher 30-day secondary patency rate, and patients treated with the ATEV were only 40% as likely to lose blood flow through their conduit after one month compared to the rate historically reported for synthetic grafts, which is a key period for recovery after traumatic injury. In addition, patients treated with the ATEV had approximately 1/5th the amputation rate, and approximately 1/9th rate of infection compared to that historically reported for synthetic grafts.

BLA Approval and Indication

On December 19, 2024, the FDA granted full approval for the ATEV for use in adults with extremity vascular trauma. The granted indication language was: “for use in adults as a vascular conduit for extremity arterial injury when urgent revascularization is needed to avoid imminent limb loss, and when autologous vein graft is not feasible.” Although Humacyte had originally filed for an indication of use that included when “autologous vein was not feasible and synthetic graft was not indicated,” the FDA granted an indication for when “autologous vein is not feasible,” a broader indication of use without the restriction of “when synthetic graft was not indicated.”

Budget Impact Model

In March 2025, the Budget Impact Model for Symvess was published in the Journal of Medical Economics. The publication reported that Symvess was projected to be cost saving for both trauma centers and third-party payers, primarily due to reductions in the costs related to amputations and conduit infections. This publication used inputs from the PROOVIT vascular trauma registry, databases of hospital charges and insurance claims, published literature (including the V005 results data published in the November 2024 JAMA Surgery article), and expert opinion to evaluate the economic impact from the perspective of Level I trauma centers and third-party commercial, Medicare and Medicaid payors. The publication was developed in collaboration with health economists and vascular surgeons to ensure that current practices in extremity arterial trauma practices were reflected, and that current health economic modeling standards were followed. Based on the model, the per-patient cost for trauma centers of treating patients with Symvess is estimated to be less than the cost of treating trauma patients with synthetic and other non-autologous grafts as shown in the graph below.

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Symvess (ATEV) Budget Impact Model

Estimated Per-Patient Cost for Trauma Centers

The model also showed greater savings for third-party payors (compared to trauma centers) due to the avoidance of late complications occurring after patients’ release from the hospital as shown in the graph below.

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Symvess (ATEV) Budget Impact Model

Estimated Per-Patient Cost for Third-Party Payors

The major drivers of cost savings in the Budget Impact Model associated with Symvess across all stakeholders were attributed to reductions in the rate of vascular conduit infection and amputation.

Proposed Indication #2: Use of the ATEV for AV Access for Hemodialysis

Overview of Hemodialysis and Existing Methods of AV Access for Hemodialysis

End-stage renal disease (“ESRD”) develops when chronic kidney disease progresses to a point where either dialysis or a kidney transplant is required for the patient to survive. For hemodialysis to be conducted, a point of vascular access to the patient’s circulatory system must be created, termed vascular access, so that blood can be transported from the body to the dialyzer and then back to the body. The demand for vascular access conduits includes the need for both new hemodialysis patients who have progressed to ESRD requiring an initial access, and existing patients that require the replacement of their existing access. There are currently three traditional methods for obtaining vascular access for hemodialysis: an AV fistula, a synthetic graft, and a catheter. Each of these vascular access methods has substantial limitations, as outlined below:

Three Traditional Methods for Obtaining Vascular Access for Hemodialysis

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Fistula. An AV fistula is created by surgically connecting a vein to an artery, typically in the patient’s arm. Fistulae are often considered the preferred means of access for hemodialysis due to lower infection rates of approximately 0.5% – 1.5% per patient-year as well as long-term durability. However, many patients are not suitable candidates for fistula placement, including women and patients with small vessel anatomy, advanced age, obesity, diabetes or other comorbidities. Approximately 40% of patients who undergo surgery for fistula creation will not gain any benefit from the surgery because the fistula lacks sufficient vein enlargement and increased blood flow, a process called fistula maturation, that is necessary for hemodialysis. Additionally, during the period in which the fistula is maturing, catheters are generally used to provide the patient access for dialysis. There is a high risk of infection and morbidity, and health care cost, associated with prolonged catheter dependence while waiting for the fistula to mature.

Catheters. A catheter, which is tunneled underneath the skin and placed directly into a large vein in the patient, is generally the least desirable access solution. Given the time necessary for fistulae to mature, the vast majority of patients in the United States begin hemodialysis using a catheter while awaiting fistula maturation. Catheters have rates of blood stream infections as high as 200% per patient-year, with high associated morbidity and health care costs.

Synthetic graft. A synthetic graft, typically made from ePTFE and sewn between an artery and vein in the patient’s arm, is generally used in patients who are not candidates for fistulae. The drawbacks of synthetic grafts include higher infection rates, which can be as high as 10% – 15% per patient-year, and gradual degradation of the non-healing ePTFE graft material caused by persistent needle punctures. A recent systematic meta-analysis measuring the functional patency of ePTFE grafts shows that, on average, only 70% of ePTFE dialysis access grafts remain functional one year after implantation.

Distribution of Hemodialysis Access Modes in Use in the United States

Access Type

Fistulae

Catheters

Synthetic Grafts

Incident Patients: At Initiation of Hemodialysis

16.7

%

80.3

%

3.0

%

Prevalent Patients: For Ongoing Hemodialysis

64.5

%

18.9

%

16.6

%

Overview of ATEV Experience in Hemodialysis Access: A table listing our clinical trials of the ATEV in hemodialysis access is included below. We have implanted the ATEV into approximately 445 total patients for hemodialysis access, for a total of more than 1,026 patient-years of exposure, as of December 31, 2025. Throughout these trials, we have observed consistent and sustained high primary and secondary patency rates. We have observed zero instances of clinical rejection of any ATEV in any hemodialysis access trial.

Implantation of ATEV for Hemodialysis

We have also observed in multiple clinical trials that our ATEVs had a low infection susceptibility during use for hemodialysis, with a rate lower than 1% per patient-year across all studies. The low infection susceptibility we observed in our trials of our ATEVs may be a result of the ATEV’s potential to become a living tissue as it becomes populated by cells from the patient’s body. Since living tissues are known to have resisted infection due to interactions with host white blood cells and immunological defense systems, it is possible that the repopulated ATEV resists infection for the same reasons that native arteries and veins resist infections, as is observed with autogenous fistulas.

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We have also observed early evidence of potential healing from the cells that repopulate the ATEV after needle puncture for hemodialysis. In examining ATEV explanted segments we have observed healed needle cannulation tracts with cells expressing smooth muscle markers. This self-healing indicates that the ATEV may have repaired itself while being used as a hemodialysis access, which we believe is a distinct feature not present in synthetic materials, and, to our knowledge, has not been observed before for any other regenerative medicine product.

Our Current Phase 2 and Phase 3 Trials of the ATEV in Hemodialysis Access

Clinical Trial

Number

Indication

Begin

Enrollment

Design/Phase

Number of

Subjects

Status

Outcomes**

V001

Dialysis Access

2012

Phase 2 Single-arm

40

Completed

30‑day PP: 95%

6‑month SP: 100%

12‑month SP: 97%

60-month SP: 58%

Infection Rate/yr: 0%

Number of Rejections: 0

V003

Dialysis Access

2013

Phase 2 Single-arm

20

Completed

30‑day PP: 95%

6‑month SP: 89%

12‑month SP: 81%

Infection Rate/yr: 4% (1 event)

Number of Rejections: 0

V006

Dialysis Access

2016

Phase 3 Prospective Randomized Blinded

355 total; 177 received ATEV 178 received ePTFE

Completed

30‑day PP ATEV: 93%

12‑month SP ATEV: 82%

24‑month SP ATEV: 67%

12‑month SP ePTFE: 80%

24‑month SP ePTFE: 74%

Infection Rate ATEV/yr: 0.93%

Infection Rate ePTFE/yr: 4.5%

Number of ATEV Rejections: 0

V007

Dialysis Access

2017

Phase 3 Prospective Randomized Blinded

242 total; 123 received ATEV, 119 received AVF

Topline results reported August 2024, two-year follow-up in process

6-month SP ATEV: 81%

12-month SP ATEV: 68%

6-month SP AVF: 66%

12-month SP AVF: 62%

V011

Dialysis Access

2019

Phase 2 (LUNA200 Manufacturing System Bridging Study)

30

Completed

30‑day PP: 97%

30‑day SP: 100%

12-month SP: 83%

Infection Rate ATEV/yr: 0%

Number of ATEV Rejections: 0

V012

Dialysis Access

2023

Phase 3 Prospective Randomized Blinded

Target 150 women total, 113 currently enrolled

Enrollment ongoing

Trial is currently enrolling, interim analysis planned on first 80 patients after one-year of follow up. The 80th patient is expected to complete one year of follow up in April 2026

** PP: Primary Patency, which is the interval of time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis, or the time of measurement of patency, i.e. patent without interventions.

SP: Secondary Patency, which is the interval from the time of access placement until abandonment, i.e. patent with or without interventions.

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Long-Term Data from Early Phase 2 Trials in Hemodialysis: V001 and V003

Phase 2 Trial Design and Current Outcomes: We have completed or are in long-term follow-up on two open-label Phase 2 trials in 60 hemodialysis patients in the United States and Poland from December 2012 through May 2014, which we refer to as our V003 trial and V001 trial, respectively. Both the V001 and V003 studies were designed as single-arm trials to assess the safety and efficacy of the ATEV for hemodialysis access, with assessments of patency at 6, 12, 18 and 24 months. In the 60 patients enrolled in these two studies, blood flow through all ATEVs was appropriate for hemodialysis, averaging over 1,200 mL/minute. Secondary patency for the two combined trials was 97% at six months, 89% at 12-months, and 81% at 18-months. These results compare favorably to published reports of secondary patency for fistula of 51% – 61% at six months and 75% at 12 months. Long-term results from the V001 trial showing five-year secondary patency of 58% were published in the European Journal of Vascular and Endovascular Surgery companion journal EJVES Vascular Forum in February 2022, and patients from the V001 trial are currently in a 10-year follow-up period.

Images and long-term results from Phase 2 V001 trial of ATEV in AV Access

Phase 3 V006 AV Access Study

Trial Design: Our V006 HUMANITY study was a prospective, multi-center, multinational, open-label, randomized, two-arm, comparative study. Eligible study subjects were randomized to receive either a ATEV or a commercially available ePTFE graft and followed to 24 months post-implantation by routine study visits. After 24 months, subjects with a patent conduit are followed to five years post-implantation using a questionnaire at six-month intervals to ascertain patient and conduit status. The primary endpoint for the V006 HUMANITY trial was a non-inferiority analysis of secondary patency compared to ePTFE, to be assessed when all subjects are at least 18 months post-implantation. There were a total of 37 sites that participated in the study, enrolling a combined total of 355 subjects.

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24-Month Results: The V006 study enrolled 355 subjects who were roughly equally matched in terms of demographics and co-morbidities. ATEV subjects trended older (p=0.06) and had more prior strokes (p=0.02) than did ePTFE subjects.

Phase 3 V006 HUMANITY trial subject demographics

V006 Demographics

(N=355)

ePTFE

(n=178)

ATEV

(n=177)

p-value

Age(years)

59.9

62.6

0.06

Male (%)

49.4%

49.7%

NS

Caucasian (%)

65.2%

69.5%

NS

Black (%)

27.5%

24.9%

NS

Hispanic (%)

11.2%

14.7%

NS

Asian / Other (%)

3.4%

2.3%

NS

Body Mass Index (BMI)

29.2

28.9

NS

Hypertension (%)

79.8%

79.7%

NS

Cardiac Disease (%)

50.6%

57.1%

NS

Diabetes (%)

29.2%

32.8%

NS

Prior Stroke (%)

5.6%

12.4%

0.02

The secondary patency of the ATEV was greater than that of ePTFE at six and 12 months but lower at 18 and 24 months, an outcome that had not been modelled in the V006 trial design. As per the pre-specified Cox Proportional Hazards test, the ATEV did not achieve its primary efficacy endpoint regarding secondary patency. In terms of safety, the ATEV had a statistically significant lower rate of conduit infections compared to ePTFE. Substantial differences in antibiotic use and need for hospitalization for infection were also noted in the V006 trial, all favoring the ATEV. The safety advantage of the ATEV over ePTFE may be clinically important as infection and sepsis are the second most common cause of death in dialysis patients.

Phase 3 V006 HUMANITY trial secondary patency results

Secondary Patency

6 months

12 months

18 months

24 months

ATEV HUMANITY [Mean (95% CI)]

92% (87 – 95%)

82% (75 – 87%)

73% (65 – 79%)

67% (59 – 74%)

ePTFE HUMANITY [Mean (95% CI)]

87% (81 – 85%)

80% (73 – 85%)

77% (70 – 83%)

74% (67 – 81%)

Cox Proportional Hazards Model for Time to Loss of Secondary Patency

Treatment Group

(ATEV vs ePTFE)

Hazard Ratio

Non-

inferiority

Margin

Hazard

Non-

inferiority

Demonstrated

(Yes/No)

Estimate

95% CI

12 months

0.869

(0.528, 1.431)

1.491

Yes

24 months

1.284

(0.867, 1.903)

1.488

No

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Phase 3 V006 HUMANITY trial rates of infection

The reported SAEs related to the ATEV and ePTFE in the V006 trial, in this patient population, which typically has a high prevalence of existing medical conditions, are detailed in the table below.

SAEs Reported in V006 Phase 3 Clinical Study in AV Access

Description of SAE

Number of SAEs

(% of total subjects)

ATEV

ePTFE

Number of subjects in V006 study

177

178

General disorders and administration conditions:

Implant site extravasation

0(0.0)%

1(0.6)%

Infections and infestations:

Vascular access site infection

0(0.0)%

5(2.8)%

Injury, poisoning and procedural complications:

Anastomotic stenosis

1(0.6)%

(0.0

)%

Vascular access site hematomas

1(0.6)%

(0.0

)%

Vascular access site hemorrhage

0(0.0)%

3(1.7)%

Vascular access site pain

1(0.6)%

0(0.0)%

Vascular access site pseudoaneurysm

10(5.6)%

0(0.0)%

Vascular access site rupture

2(1.1)%

0(0.0)%

Vascular access site thrombosis

41(23.2)%

28(15.7)%

Skin and subcutaneous tissue disorders:

Skin necrosis

0(0.0)%

1(0.6)%

Vascular disorders:

Steal syndrome

2(1.1)%

2(1.1)%

Subclavian vein occlusion

0(0.0)%

1(0.6)%

Vascular stenosis

34(19.2)%

27(15.2)%

Venous stenosis

3(1.7)%

9(5.1)%

Overall, although the primary efficacy endpoint concerning secondary patency was not met, the ATEV otherwise performed in the V006 trial as was expected, based upon ATEV performance in previous Phase 2 trials in hemodialysis and in other clinical applications. This outcome was due at least in part to unexpectedly high patency of the ePTFE grafts, particularly after 12 months. While the cause of this unexpectedly high patency is not clear, it is possible that study-mandated ultrasounds and examinations may have led to more aggressive vigilance with ePTFE grafts to maintain patency. In addition, the age and comorbidities of ATEV subjects in V006 was somewhat worse than for ePTFE subjects.

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In the V006 trial, the ATEV displayed significantly fewer infections than did the ePTFE grafts. This was associated with fewer instances of immune sensitization in ATEV subjects as compared to ePTFE subjects, which could translate to easier kidney transplantation at future times. Similar to prior studies, we observed that the ATEV had good durability, blood flow rates and diameters similar to ePTFE grafts, and also host cell remodelling that was superior to that of ePTFE grafts.

Phase 3 V007 AV Access Study

Trial Design: In April 2023 we completed enrollment of a Phase 3 trial, called V007, in 242 patients with ESRD. V007 is a Phase 3, prospective, multi-center, open label, randomized, two-arm comparative study conducted in the United States. The V007 trial is designed to assess the usability of the ATEV for dialysis at six and 12 months as a comparison to autogenous fistulas, which are known to exhibit a high rate of early maturation failure of approximately 40% at six months. Patients in the study are randomized to receive either the ATEV for vascular access or an autogenous AV fistula. The objective of V007 is to compare the safety and efficacy of our 6 millimeter ATEV to autogenous AV fistula for functional hemodialysis access.

Eligible study subjects in V007 are randomized to receive either an ATEV or an autogenous fistula and followed to 24 months post-implantation by routine study visits. Efficacy endpoints include useability for dialysis at six and 12 months, as well as a comparison of secondary patency via a time-to-event analysis of all subjects at 12 months. Additional safety endpoints include the rate of dialysis access-related infections for ATEV and fistula subjects.

One-Year Results: As of December 31, 2024, there were 242 patients enrolled in the V007 trial, and enrollment was completed in April 2023. Demographics of the patients enrolled in V007 are summarized in the following table.

Phase 3 V007 trial subject demographics

ATEV (N=123)

AVF (N=119)

ITT Set

123

119

Safety Set*

121 (98%)

121 (102%)

Females

37 (30%)

33 (28%)

Whites

73 (59%)

86 (72%)

Age, mean (min, max)

57.1 (24, 82)

60.1 (21, 87)

Age ≥ 65

43 (35%)

44 (37%)

BMI ≥ 30

52 (42%)

42 (35%)

BMI mean value (min, max)

30.2 (19, 49)

29.1(17, 49)

History of Diabetes

82 (67%)

83 (70%)

__________________

* Two patients randomized to ATEV received an arteriovenous fistula (“AVF”) and were analyzed as AVF in the Safety Set

ITT = Treatment group assignment based on randomization.

Safety Set = Treatment group assignment based on actual treatment.

Topline results were reported in August 2024 and expanded results, including subgroup analyses, were presented at the American Society of Nephrology’s (“ASN”) Kidney Week 2024, the premier nephrology meeting, in October 2024. In the V007 trial, the ATEV demonstrated superior function and patency at six and 12 months (co-primary endpoints) compared to AVF, the current standard of care for hemodialysis, as summarized in the following table.

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Phase 3 V007 trial 12-month results (all patients)

Co-Primary Endpoints

ATEV (n=123)

AVF (n=119)

p-value

Functional Patency at Month 6

81.3%

66.4%

0.0071

Secondary Patency at Month 12

68.3%

62.2%

Difference

p-value

Duration of Use Over First 12 Months

7.5 months

6.1 months

1.4 months

0.0162

Safety events per year of usability in the V007 Phase 3 trial are summarized in the following table.

Phase 3 V007 trial safety results (all patients)

12-Month Safety Summary

ATEV

AVF

Subjects (%) n=121

Events Per Patient Year

Subjects (%) n=121

Events Per Patient Year

Treatment Emergent Adverse Events

98.3%

16.0

96.7%

13.5

Serious Adverse Events

81.8%

5.1

61.2%

3.5

Adverse events of special interest:

Study access (SA)-related infections

Thrombosis

Stenosis

Clinically significant Steal Syndrome

Rupture of SA

Leading to SA revision or ligation

Leading to SA excision

5.8%

52.9%

66.1%

0.8%

0.0%

11.6%

4.1%

0.1

1.7

3.0

0.0

0.0

0.3

0.1

4.1%

9.1%

47.9%

5.8%

1.7%

24.0%

1.7%

0.1

0.2

1.9

0.1

0.0

0.7

0.0

The largest area of difference in AEs was in thrombosis. The majority of ATEV patients with thrombosis, 94%, were successfully treated.

Sub-group analysis was also performed in patient groups that historically have poor outcomes with AV fistula procedures. In female patients, subjects implanted with the ATEV had significantly higher six-month and one-year patency rates than female patients receiving an AV fistula as summarized in the table below.

Phase 3 V007 trial 12-month results (female patients)

Co-Primary Endpoints

ATEV (n=37)

AVF (n=33)

p-value

Functional Patency at Month 6

89.2%

54.5%

<0.0001

Secondary Patency at Month 12

81.1%

48.5%

Difference

p-value

Duration of Use Over First 12 Months

8.3 months

5.0 months

3.3 months

0.0011

It was also noted in the V007 trial that obese patients (BMI of at least 30) (n=93) implanted with the ATEV had significantly higher six-month and one-year patency rates than obese patients receiving an AV fistula. In addition, diabetic patients implanted with the ATEV had significantly higher six-month and one-year patency rates than diabetic patients receiving an AV fistula. Based on these results, we consider the subgroup of females and males with obesity and diabetes (a subgroup that combined

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represents over half of dialysis patients), to be a target population that could benefit from the ATEV. Results through 12 months of follow up from the V007 trial in females and males with obesity and diabetes are summarized in the following table.

Phase 3 V007 trial 12-month results – target population

(female patients and males with obesity and diabetes)

Co-Primary Endpoints

ATEV (n=56)

AVF (n=54)

p-value

Functional Patency at Month 6

85.7%

51.9%

<0.0001

Secondary Patency at Month 12

76.8%

46.3%

Difference

p-value

Duration of Use Over First 12 Months

8.0 months

4.5 months

3.5 months

0.0002

The ATEV showed no increased in overall safety events per year of usability in the expected target population (all females and males with obesity and diabetes) as summarized in the following table.

Phase 3 V007 trial safety results – target population

(female patients and males with obesity and diabetes)

12-Month Safety Summary

ATEV

AVF

Subjects (%) n=54

Events Per Patient Year

Subjects (%) n=56

Events Per Patient Year

Treatment Emergent Adverse Events

96.3%

14.8

98.2%

21.8

Serious Adverse Events

77.8%

4.2

67.9%

6.1

Adverse events of special interest:

Study access (SA)-related infections

Thrombosis

Stenosis

Clinically significant Steal Syndrome

Rupture of SA

Leading to SA revision or ligation

Leading to SA excision

7.4%

51.9%

64.8%

1.9%

0.0%

11.1%

5.6%

0.1

1.2

3.0

0.0

0.0

0.2

0.2

5.5%

12.5%

51.8%

3.6%

3.6%

28.6%

3.6%

0.1

0.3

2.9

0.1

0.1

1.2

0.1

In November 2025, two-year results from the V007 trial were presented at the ASN Kidney Week 2025. The V007 study had a secondary endpoint of duration access use over 24 months, for which the ATEV was observed to have superior duration of access compared to AV fistula in female, obese and diabetic patients. In female patients (n=70) over 24 months, patients implanted with the ATEV had 15.8 months of average duration of access, compared to 10.0 months for patients receiving an AV fistula (p<0.0137). In the target population of females, and males with obesity and diabetes (n=110), patients implanted with the ATEV had 14.8 months of average duration of access use compared to 9.1 months for patients receiving an AV fistula (p=0.0114). For all patients in the study (n=242), patients receiving an ATEV had 13.3 months of average duration of access use compared to 12.3 months for AV fistula (p=0.7446). The results are consistent with our strategy of targeting patients at higher risk of AV fistula failure: females, and males with obesity and diabetes, which comprise over half of the hemodialysis population.

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Phase 3 V012 AV Access Study in Women

In collaboration with our corporate partner Fresenius Medical Care and its subsidiary Frenova Renal Research, we conducted a study to review the outcomes of 178,575 adult patients who received in-center dialysis at Fresenius Kidney Care dialysis centers. Among the areas of study were the complications and cost of treatment by patient demographic. The objective of the study was to further define patient subgroups who could most benefit from the ATEV. The study showed that women, particularly obese and diabetic women, have higher complication rates, including infections and access failures, and higher treatment costs.

Based on the results of this research, we designed a clinical study designed to demonstrate the clinical and health economic benefits of the ATEV in women dialysis patients, a high-unmet-need population. We commenced the Phase 3 trial, which we refer to as the V012 trial, in up to 150 patients with ESRD. V012 is a Phase 3, prospective, multi-center, open label, randomized, two-arm comparative study conducted in the United States. The V012 trial is designed to assess the usability of the ATEV for dialysis in comparison to autogenous fistulas, in female patients currently receiving hemodialysis via catheter. The primary measure of efficacy will be total days free from in-dwelling catheter (“catheter-free days”) until 365 days, or until access abandonment, whichever occurs first. The primary measure of safety will be the number and severity of infections related to all accesses (including catheters) from access creation until 365 days. An interim analysis is planned on the first 80 patients after one-year of follow up, and 113 patients have currently been enrolled in the study. The 80th patient from V012 is expected to complete one year of follow up in April 2026 and we expect to report top-line interim results from the trial in the second quarter of 2026.

Planned Supplemental BLA Filing in AV Access

Based on discussions with the FDA, our current plan is to submit a supplemental BLA after interim analysis of V012 study, subject to the results of that interim analysis. This plan would support a supplemental BLA submission in the second half of 2026 dependent upon the timeline for interim data analysis. Our current expectation is that the supplemental BLA submission would target the subgroups in which the ATEV has showed the best results to date, which are all females and males with risk factors for fistula non-maturation.

Proposed Indication #3: PAD

PAD involves partial or complete occlusion of blood vessels in the peripheral circulation and is a major cause of morbidity and mortality in the developed world. Patients with severe PAD undergo peripheral arterial bypass surgery where a conduit is implanted above and below the area of the arterial obstruction, to provide a “bypass” route for blood to flow around the blocked artery. The vast majority of these operations are performed in the lower limb. Other surgical alternatives include minimally invasive approaches such as stenting and angioplasties that are suitable for smaller atherosclerotic lesions and can delay — but oftentimes not prevent — the ultimate need for surgical revascularization.

We have observed strong patency rates and no reported cases of infection for the ATEV in PAD in clinical studies to date. We are developing our 6 millimeter ATEV for use as a bypass conduit for patients with PAD. We have conducted two Phase 2 trials to evaluate the safety and efficacy of our 6 millimeter ATEV for use as a bypass conduit with PAD, which we refer to as our V002 and V004 trials. For both of these Phase 2 trials, the ATEV was implanted as a femoral popliteal bypass graft in patients with PAD.

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Our Current Phase 2 Trials of the ATEV in PAD

Clinical

Trial

Number

Indication

Begin

Enrollment

Design/

Phase

Number of

Subjects

Status

Outcomes**

V002

Peripheral

2013

Phase 2

20

10-year

30-day PP: 100%

Artery Disease

Single-arm

follow-up

6-month SP: 84%

ongoing

12-month SP: 84%

72-month SP: 60%

Infection Rate/yr: 0%

Number of Rejections: 0

V004

Peripheral

2016

Phase 2

15

Completed

30-day PP: 100%

Artery Disease

Single-arm

6-month SP: 86%

12-month SP: 64%

Infection Rate/yr: 0%

Number of Rejections: 0

Number of Amputations: 0

** PP: Primary Patency, which is the interval of time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis, or the time of measurement of patency, i.e. patent without interventions.

SP: Secondary Patency, which is the interval from the time of access placement until abandonment, i.e. patent with or without interventions.

Trial Design: Both our V004 and V002 trials were prospective, open-label, single treatment arm, multi-center studies. We enrolled 20 patients in our V002 trial in Poland, and 15 patients in our V004 trial in the United States. Both trials had the primary objectives of evaluating the safety of the ATEV as a femoral-to-popliteal bypass graft, and determining the primary, primary assisted, and secondary patency over 12 and 24 months.

Current Trial Status and Outcomes: V002 enrolled a total of 20 patients between the ages of 54 and 79 at three clinical sites. 24-month results of the V002 trial were published in 2020. After censoring for three deaths (none of which were determined to be related to the ATEV or the implant procedure), we observed 24-month primary, primary assisted and secondary patency rates of 58%, 58%, and 74%, respectively. We observed through ultrasound data that the ATEVs were mechanically stable during the follow-up period and did not develop aneurysmal dilatation in any patient. Overall, we also determined through the histological assessment of explanted specimens that there were normal vascular cells within the ATEV and there was no infection or signs of immunological reaction to the graft.

There have been no ATEV-related infections reported during the V002 trial as of December 31, 2025, and no amputations of the treated extremity. A sub-set of seven V002 subjects consented for long-term follow-up computerized tomography (“CT”) angiograms, which were obtained at 48 to 52 months after ATEV implantation. In all cases, the ATEV maintained normal architecture and function. A representative image is shown below, taken 50 months post-implantation. Proximal and distal anastomoses of ATEV with recipient’s vasculature are noted, as is the scale bar on the right-hand side of each image. The image presents two views of the same subject, and shows uniform ATEV diameter along the length of the implant.

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A CT Angiogram from a V002 Subject at 51 months after ATEV implantation

Patients in the V002 trial are currently in long-term follow-up out to ten years. In 2022, six-year results from V002 were published in Journal of Vascular Surgery – Vascular Science. The article, entitled “6-Year Outcomes of a Phase 2 Study of Human-Tissue Engineered Blood Vessels for Peripheral Arterial Bypass,” reported overall secondary patency rate of 60% at 72 months, including all patients originally enrolled, as estimated by Kaplan Meier analysis. There was no evidence of graft rejection or infection, and no patients underwent amputation of the affected limb out to six years.

Long-term results from V002 Phase 2 study in PAD

Result from V002

Phase 2 Trial in PAD

(as of April 2021)

Pre-Op

1 yr

2 yr

3 yr

4 yr

5 yr

6 yr

Avg

Secondary Patency

—

84%

74%

73%

66%

60%

60%

—

Ankle-Brachial Index (median)

0.64

0.90

0.96

—

1.07

0.98

0.94

(n=2)

0.97

(post-op)

ATEV Infection Rate

—

0%

0%

0%

0%

0%

0%

0%

The V004 trial enrolled 15 subjects in the United States, with the 12-month follow-up of the last enrolled patient occurring in December 2020. Patients in the V004 trial included Rutherford 4 and 5 subjects, with severe, debilitating limb ischemia. (Rutherford 4 and 5 patients are classified as patients with pain at rest due to limb ischemia (stage 4), and those patients suffering tissue loss in the limb as a result of ischemia (stage 5)). In addition, enrollment in V004 required that no autologous vein be available for bypass. Hence, the subjects enrolled in the V004 trial had severe and debilitating limb ischemia due to PAD and had no autologous vein that was suitable for lesion bypass and revascularization.

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12-month results from V004 Phase 2 study in PAD

Result from V004 Trial (as of April 2021)

Pre-Op

6 mos

12 mos

Secondary Patency

—

86%

64%

Ankle-Brachial Index (median)

0.51

0.85

0.90

Rate of Amputation

—

0%

0%

VascuQol Quality of Life Assessment

3.1

5.6

5.9

In the V004 trial, ATEV secondary patency was 86% at 6 months, and 64% at 12 months. While lower than patency values observed in the V002 trial, patients in the V004 trial had more severe PAD, which is associated with poorer arterial “run-off” and higher propensity for conduit occlusion. Assessment of Quality of Life by the validated VascuQol assessment demonstrated an increase in overall quality of life for V004 patients at 6 and 12 months. In addition, ankle-brachial index, a measurement of blood pressure in the operative limb, was increased at 6 and 12 months. There were no infections of the ATEV reported in the V004 trial, despite the severity of the PAD and the often-associated tissue infection that can accompany this disease. There were zero reports of clinical ATEV rejection. Lastly, there were zero reported amputations of any operative limb in the first 12 months of follow-up.

Published literature reports of patients with Rutherford stage 4 and 5 PAD and no autologous vein available for revascularization show that outcomes can include amputation. For Rutherford 4 and 5 patients with no vein and no revascularization procedure, amputation rates at 6 months are reported at 31%. For stage 4 and 5 patients who do undergo saphenous vein revascularization, the amputation rate at one year is approximately 10%. The lack of amputation for stage 4 and 5 patients in the V004 trial at one year, none of whom had saphenous vein for revascularization, supports the use of the ATEV in severe PAD.

Examples of the Use of Our 6 millimeter ATEVs in Expanded Access Cases

The FDA granted use of the ATEV in 30 special expanded access cases prior to the December 2024 FDA approval in extremity vascular truama, the majority of which were patients with chronic limb-threatening ischemia (“CLTI”), the end stage of PAD. Each of these compassionate use cases was conducted under an individual, investigator-initiated IND application with the FDA. Two cases are highlighted below.

70-year-old with Critical Limb Ischemia

The patient is a 70-year-old male with critical limb ischemia and no vein available to perform a bypass, as the vein was previously used for a CABG. He underwent a successful bypass with the ATEV. Imaging at one year demonstrated a patent graft as illustrated below.

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42-year-old with Infected Dacron Graft

An ATEV was used in a 42-year-old female to replace an 8 mm Dacron iliac artery bypass graft that had become infected. The patient refused harvesting of the femoral vein for reconstruction and requested the ATEV. The patient was seen at one, three, six, nine, and 12 months after ATEV implantation. At all visits, the ATEV appeared normal with unobstructed patency. Flow and velocities were normal. At three months, the patient was released to full activity. At six and 12 months, the graft was functioning well. At one-year imaging, the ATEV was patent and appeared remarkably similar to the patient’s native blood vessels. The patient had no signs of infection in the ATEV and continues to have no limitations or complications during normal activity or exercise.

Mayo Clinic Study in Severe PAD

The Mayo Clinic, Rochester, MN, conducted a study in patients with CLTI under an investigator-initiated IND filed with the FDA. In February 2024, researchers published interim results in the Journal of Vascular Surgery, including their conclusion that in the clinical study the ATEV was a safe, resilient, and effective conduit for arterial bypass and limb salvage. This is an important result since approximately 40% of patients requiring lower extremity bypass do not have saphenous vein available, which is the standard of care for treating this challenging disease state. The presentation reported the outcomes of 29 patients, with a mean age of 71 and having no available vein to use as a bypass graft, who underwent ATEV implantation. Of these 29 patients, 28 (97%) had previously experienced unsuccessful revascularization procedures on the extremity and 21 (72%) had tissue loss or gangrene. Based on the state of this disease, this patient group had a 30-50% one-year risk of amputation. Notably, performing bypass surgery in 24 (83%) of the patients necessitated the fusion of two 42 cm long ATEVs to achieve the required bypass length. Surgeons reported that the operations to implant the ATEV achieved a 100% technical success rate, without any ATEV-related major adverse events reported. At a median follow-up of nine months, the secondary patency rate for patients implanted with the ATEV was 71%. The limb salvage rate was 86%, corresponding to only a 14% amputation rate.

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Preclinical Pipeline

Pancreatic Islet Transplantation for Type 1 Diabetes (BioVascular Pancreas)

The BVP is a modification of Humacyte’s ATEV product, leveraging the ATEV to deliver therapeutic cells within close proximity of the patient’s bloodstream. We believe that the ATEV extracellular matrix material is both highly biocompatible, as evidenced by adaptive cellular repopulation after implantation, and also highly angiogenic, as evidenced by extensive formation of microvessels surrounding the ATEV in vivo. These attributes mean that the ATEV may serve as a suitable conduit for delivering large numbers of therapeutic cells to a patient.

Pancreatic islets, which sense blood glucose and respond by secreting insulin, are destroyed by an auto-immune attack in patients with Type I diabetes. The outer surface of our 42cm ATEV has sufficient surface area to accommodate a monolayer of approximately 800,000 human pancreatic islets, which is approximately the number in an entire adult pancreas, and can reverse diabetes and restore glucose control.

We have performed mathematical modelling studies that predict, we believe, that a 42cm ATEV could maintain viability of a therapeutic number of islets after implantation of the ATEV into the arterial bloodstream, or after implantation as an AV conduit similar to that used for hemodialysis access. Bioreactor experiments have confirmed these mathematical conclusions. Furthermore, we have implanted rat-sized BVPs into the aortas of diabetic rats, and observed that the BVP could restore normal glucose levels in all treated animals, while control animals (“No Flow” in red in figure below) did not restore glucose control.

In April 2023, Humacyte and Breakthrough T1D (f/k/a JDRF International) (“JDRF”), the leading global organization funding type 1 diabetes research, announced a collaboration to advance the development of the BVP product candidate. During 2023 and 2024, we performed testing the BVP in primates. In these experiments, researchers observed that insulin-producing cells in the BVP survive for months after implantation into the animal and continue to make insulin after implantation that is measurable in the bloodstream. We consider these results to be extremely encouraging as they support the potential ability of the BVP to deliver a curative number of insulin-producing islets into diabetic subjects. Additional work in large animals is currently ongoing, including using the BVP in diabetic large animals.

Coronary Artery Bypass Graft

Evaluation of 3.5-4mm diameter blood vessel, the coronary tissue engineered vessel (“CTEV”) for CABG has been performed over the last five years at Humacyte. We performed a preclinical study at Duke University to evaluate the use of our small diameter CTEV for CABG in adult primates (baboons), and we have also performed studies of the CTEV in sheep and pig models of CABG surgery, with follow-up times ranging from 1-3 months. The goal of the primate and other large animal studies is to assess patency and function of the small diameter CTEV, as well as host responses and cellular remodeling. CTEVs are followed by ultrasound imaging of the heart, and angiographic imaging of the conduits. In September 2025, preclinical results of the CTEV in a baboon model of CABG were published in JACC: Basic to Translational Science, a specialist journal launched by the Journal of the American College of Cardiology (“JACC”). In the six-month preclinical CABG model, the CTEV was observed to sustain patency (blood flow), recellularized with the animals’ host cells, and remodeled to effectively reduce the

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initial size mismatch between the CTEV and the animals’ native artery. In the preclinical study, the CTEV was implanted between the aorta and right coronary artery (“RCA”) in five baboons to simulate a CABG procedure. Animals were followed for six months after CTEV implantation and all CTEVs maintained patency throughout the study. The baboon study provided an effective model for demonstrating the feasibility, mechanical durability and capacity for host-cell remodeling of the CTEV for CABG. After implantation, the CTEV was observed to recellularize with host cells and remodel to effectively reduce the initial size mismatch with the RCA.

Angiography showing adaptive remodeling

of ATEV after implant in baboon CABG model

We plan to commence, dependent on clearance of an IND by the FDA, the first human clinical testing of the CTEV in CABG in the second half of 2026.

Pediatric Heart Surgery: Modified Blalock-Taussig-Thomas (mBTT) Shunt

Tetralogy of Fallot is a relatively common congenital heart defect, that is often treated using a modified Blalock-Taussig-Thomas (“mBTT”). To support a potential future IND filing with the FDA, we have evaluated the use of our CTEV as an mBTT shunt for up to six months in juvenile primates at the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio.

BT Shunt Implant Schematic

In October 2023, results of the preclinical study were published in the open-access Journal of Thoracic and Cardiovascular Surgery (JTCVS Open). In the study, researchers implanted 3.5mm diameter CTEVs into a juvenile large-animal model of pediatric heart disease. The 3.5mm CTEV was implanted between the subclavian and pulmonary arteries, to mimic a commonly-performed surgical procedure used to treat babies born with Tetralogy of Fallot, one of the most common pediatric heart conditions. The study assessed the CTEV’s patency, structure, and blood flow from one week to six months after the implant.

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The 3.5mm diameter CTEV has smaller product dimensions but is manufactured using a similar process as Humacyte's 6mm CTEV system currently being evaluated in clinical trials in vascular trauma, AV access for hemodialysis, and PAD. We believe that the production of the functional 3.5mm CTEV is indicative of the potentially broad application of our proprietary bioengineered tissue platform and manufacturing processes.

Engineered Trachea for Treatment of Severe Airway Injuries

Each year in the United States, approximately 4,000 operations are performed to repair or reconstruct the trachea or mainstem bronchi. But unlike most other connective tissues in the body — such as blood vessel, bone, skin and tendon — there currently are no replacements for tracheal tissue that are in widespread clinical use. For long tracheal or bronchial defects, some sort of tracheal replacement is often needed, yet none exists currently. The lack of a functional tracheal conduit commits patients to, sometimes, slow suffocation.

We have modified the ATEV production process to enable the embedding of a biocompatible medical-grade stent within the wall of the engineered vessel. Combining a non-degradable stent with the degradable polymer scaffold used for ATEV production results in a composite scaffold that can be seeded with smooth muscle cells and grown in culture. After decellularization, the engineered trachea consists of the extracellular matrix contained in the ATEV, along with an embedded stent that prevents the collapse of the engineered airway with inspiration or neck movements.

Summary of Process to Generate Engineered Tracheas

In models where engineered tracheas were implanted into rats and non-human primates, we have observed that the implants repopulate with cells from the host, including cuboidal respiratory epithelium that lines the native airway progressively from two to eight weeks after implantation. We have further observed that the engineered tracheas can function out to two months. Future studies in large animal models are planned.

Photograph (A) of Implantation of Engineered Trachea into Non-Human Primate Airway; Microscope Imaging of Cells Repopulating the Trachea after 2 and 8 weeks (B, C)

Engineered Whole Lung Organs

End-stage lung disease is the fourth leading cause of death in the U.S., and lung transplantation remains severely limited by donor organ shortages. Dr. Niklason’s laboratory at Yale University has pioneered the development of using decellularized native lungs, combined with targeted recellularization of the lung scaffolds within biomimetic bioreactors, to produce whole lungs that are capable of exchanging gas. Gas exchange for several hours has been observed in studies in rodents. Efforts to scale-up the technology to human-sized organs are ongoing.

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Structure of Lung, Scaffold for Lung Engineering, and Implanted Engineered Lung

Manufacturing

We have developed a novel paradigm for manufacturing human tissues that mimics key aspects of human physiology. Recognizing that commercial scale production capacity of bioengineered tissue has been non-existent, we prioritized the development of a scalable, reproduceable, commercial biomanufacturing process. At our 83,000 square foot manufacturing facility in Durham, North Carolina, we have industrialized this concept and created a scalable modular manufacturing process that enables us to engineer our ATEVs in commercial quantities in a system designed for cGMP compliance.

Our proprietary manufacturing process was designed with a modular approach allowing us to produce ATEVs in smaller batches for clinical trials and scale out to larger batches for commercial manufacturing. The current, commercial-scale LUNA200 system utilizes 20 growth drawers holding ten ATEVs each for a total of 200 ATEVs per batch. Since 2021 this system has been utilized to produce clinical product for use in our ongoing Phase 3 trials. The FDA inspected our manufacturing facility in April 2024 as part of its review and approval of our BLA in extremity vascular trauma, and we are using this facility to provide product for the United States commercial launch in that indication which commenced in the first quarter of 2025.

Our manufacturing process utilizes our LUNA200 system, consisting of 20 “growth drawers.” Each growth drawer is capable of producing ten 42cm ATEVs and each ATEV remains contained within an individual bioreactor bag. Inside a LUNA200, a closed tubing network connects all 20 growth drawers as well as the ten bioreactor bags in each drawer, allowing the entire system to share cells and nutritive media. In this way, a single LUNA200 can produce up to 200 ATEVs per batch while maintaining the critical operating parameters that direct growth, creating a gross capacity of approximately 900 ATEVs per system annually.

We have designed the LUNA200 to have the ability to produce ATEVs in diameter sizes from 3mm to 10mm and lengths from 10cm to 42cm, making the equipment suitable for the varied array of product candidates in our pipeline. We are also developing a smaller diameter CTEV for CABG and pediatric heart surgery. We intend to introduce a 13cm ATEV line extension after commercial launch of the 42cm ATEV. Using our existing LUNA manufacturing equipment, we can generate 400 13cm ATEVs per batch. Our modular manufacturing platform can be scaled without impacting the operating parameters that support the ATEV growth process. We have designed our manufacturing system to be functionally closed, to utilize single-use disposable materials with aseptic connections, and to be fully automated.

We currently have eight LUNA200 systems installed, commissioned and qualified in our manufacturing facility, creating an annual gross ATEV capacity of approximately 7,200 ATEVs. Our manufacturing facility contains space to increase capacity in future years to approximately 40 LUNA200 systems in total. As we continue to expand production, we believe that we will have the ability to take advantage of economies of scale and reduce production costs. The initiation and pace of the expansion of vessel capacity will be determined based on our assessment of market opportunity.

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We initiate ATEV production using primary human aortic vascular cells from a working cell stock (“WCS”) that is isolated from FDA-compliant donor tissues and cryopreserved. The WCS vials are stored at two separate qualified facilities to mitigate the risk of single site storage. We qualify all new WCSs for use in ATEV manufacturing utilizing biochemical and gene expression assays. Each qualified primary isolation can produce approximately 500,000 to one million ATEVs.

The WCS expanded using traditional cell culture techniques, and the cells are transferred onto a biocompatible, biodegradable polymer mesh within a flexible, single-use bioreactor bag. Cells inoculated onto this tubular mesh are cultured utilizing a proprietary culture medium and subjected to cyclic mechanical stretch for a period of approximately eight weeks. During this period, the cells proliferate and build extracellular matrix while the polymer mesh degrades. The resulting bioengineered vessel is comprised of the aortic vascular cells and their deposited extracellular matrix. After completion of the culture period, we decellularize the bioengineered vessel using a proprietary combination of salts, enzymes and detergents, followed by numerous washes in excipient grade neutral pH buffered saline. The resulting ATEV retains the human extracellular matrix constituents and, therefore, the biomechanical properties of the bioengineered vessel, but cells and cellular components, which could induce a foreign body response or immune rejection following implantation, are removed. After decellularization, our ATEVs are packaged for distribution inside the same flexible bioreactor bag in which they were produced, with sterile phosphate buffered saline as the excipient. Once the package is delivered to the operating room, the ATEV is removed from the bioreactor bag by the surgical staff.

Suppliers

We source critical components and necessary raw materials from vendors that have been approved and qualified through our vendor management program. SeraCare, which was subsequently acquired by LGC Clinical Diagnostics, Inc. (“SeraCare”), is the current single source supplier of human plasma used in our manufacturing process and Confluent Medical Technologies, Inc. (“Confluent”) is the current single source supplier of the polymer mesh we use. We source custom, Humacyte-designed, pre-sterilized (gamma irradiated) assemblies and single-use tubing sets through multiple approved vendors. We source bioprocess solutions, including culture media and decellularization buffers, from a division of Thermo Fisher Scientific, which has a second production site to provide redundant media/buffer production capacity. We continue to explore the development redundant vendors for all critical materials and we manage all vendor changes through a robust change control process.

Supply Agreement with SeraCare

In January 2014, we entered into a supply agreement with SeraCare for the supply of human plasma, which was amended in October 2018 and March 2021 (as amended, the “SeraCare Agreement”). Under the SeraCare Agreement, we agreed to purchase at least a substantial majority of our human plasma requirements from SeraCare. In the event SeraCare is unable to fulfill our requirements, and subject to certain conditions, we may engage another plasma supplier during the period in which SeraCare is unable to fulfill our requirements. The SeraCare Agreement is subject to annual price modifications in the case of significant changes in SeraCare’s cost of raw materials, with any modification to be determined at least three months prior to the end of the relevant year. The initial term of the SeraCare Agreement expired on October 12, 2023, but automatically extends for subsequent one-year periods unless terminated by either party at least 18 months prior to the end of the initial term. Either party may terminate the SeraCare Agreement for uncured material breach or for the insolvency of the other party at any time. In addition, either party may terminate the SeraCare Agreement without cause upon 12 months’ written notice. We may also terminate the agreement in the event of certain supply interruptions. Each party also agreed to indemnify the other against certain third-party claims up to a specified cap.

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Supply Agreement with Confluent

In August 2015, we entered into an agreement for the supply of polymer mesh, which we refer to as the mesh supply agreement, with Biomedical Structures LLC (“Biomedical Structures”). Biomedical Structures’ rights and obligations under the mesh supply agreement were subsequently assigned to Confluent in connection with Confluent’s acquisition of Biomedical Structures in 2016. In 2020, the agreement was amended to align with the growth expected with the transition to commercial distribution following FDA approval. Pursuant to the mesh supply agreement, the price of polymer mesh we purchase from Confluent is subject to potential adjustment if Confluent’s cost of raw materials increases above a specified threshold pursuant to good faith negotiations from both parties, which negotiation Confluent may not request more than once in a 12-month period. The 2020 amendment also provided volume driven discounts. Confluent is obligated to partner with Humacyte in order to establish redundant facilities for the manufacture of the polymer mesh at established contractual volume thresholds. The amended mesh supply agreement has a term of three years, which can be automatically extended for subsequent one-year periods and will continue to do so unless either party provides notice of non-renewal at least 120 days prior to the end of the then-current term or otherwise terminates in accordance with the agreement. We and Confluent are each also permitted to terminate the mesh supply agreement for convenience, however Confluent must provide us with at least 365 days written notice and we are obligated to provide 180 days’ notice, prior to such a termination. In addition, each party is permitted to terminate the mesh supply agreement for an uncured material breach by the other party following failure to remedy the breach during a sixty-day cure period. Both parties have agreed to indemnify one another for certain third-party claims.

Distribution

Commercialization Strategy Within United States and for Earlier-Stage Pipeline Programs

Following the December 2024 FDA approval of Symvess in extremity vascular trauma, we commenced the United States commercial launch in that indication in the first quarter of 2025. For our vascular repair and replacement applications of our technology, including vascular trauma, AV access for dialysis, and the treatment of PAD, we have retained the right to commercialize our ATEV within the United States. In the United States we are commercializing the ATEV through our own direct sales and marketing team and expect to do so also for any additional ATEV indications that may be approved. We own end-to-end commercialization and are pursuing collaborations with appropriate strategic partners who have established distribution channels for specialized markets.

Our first market launch of Symvess for the treatment of extremity vascular trauma in the United States involves a highly concentrated market of approximately 200 Level I Trauma Centers that may be reached with a small field sales forces, currently 12 field sales executives. Many of the major trauma centers already have familiarity with our ATEVs through their participation in our clinical trials. Our sales launch commenced in the first quarter of 2025 and includes dual targeting of surgeons to create pull-through demand and hospital administration (trauma center Value Analysis Committees) to ensure adoption and uptake of the ATEV in vascular trauma.

We have developed and published a Budget Impact Model based on the clinical results supporting the approval of Symvess, and the estimated reduction in clinical complications potentially achievable by treating specific patients with Symvess versus current standard of care. Based on the model, the per-patient cost of treating patients with Symvess is estimated to be less than the cost of treating trauma patients with synthetic grafts, cryopreserved allografts, or xenografts, as well as other patients at high risk of complications. Major drivers of cost savings associated with Symvess were attributed to reductions in the rate of amputation and vascular conduit infection.

The DoD assigned a priority designation to the ATEV technology under Public Law 115-92 and provided an approximately $6.8 million grant from the DoD for the development of our ATEVs for vascular reconstruction and repair. The fiscal year 2026 DoD Appropriations Act includes dedicated funding to support the evaluation and incorporation of biologic vascular repair technologies for the warfighters suffering from traumatic vascular injuries.

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We expect that the large market potential of earlier-stage applications of our technology platform such as CABG and BVP for diabetes will provide additional collaboration opportunities, and we expect explore strategic partnerships for these product candidates as preclinical and clinical results providing additional proof of concept are generated.

Distribution Agreement with Fresenius Medical Care

We entered into a distribution agreement with Fresenius Medical Care in June 2018 which, as amended as of February 16, 2021, granted Fresenius Medical Care and its affiliates exclusive rights to develop outside the United States and European Union (the “EU”) and commercialize outside of the United States our 6 millimeter x 42cm ATEV and all improvements thereto, and modifications and derivatives thereof (including any changes to the length, diameter or configuration of the foregoing), for use in vascular creation, repair, replacement or construction, including renal replacement therapy for dialysis access, the treatment of PAD, and the treatment of vascular trauma, but excluding coronary artery bypass graft, pediatric heart surgery, or adhering pancreatic islet cells onto the outer surface of the distribution product for use in diabetic patients. Within the United States, Fresenius Medical Care will collaborate with Humacyte in its commercialization of the product in the field, including adoption of the distribution product as a standard of care in patients for which such use is supported by clinical results and health economic analyses.

We are responsible for developing and seeking regulatory approval for the distribution product in the field in the United States. For countries outside the United States, the parties agreed to use commercially reasonable efforts to satisfy certain agreed minimum market entry criteria for the distribution product in the field in such country. For the EU, once such criteria have been satisfied for the applicable country, or if the parties otherwise mutually agree to obtain regulatory approval for the distribution product in the field in the applicable country, we agreed to use commercially reasonable efforts to obtain such regulatory approval (other than pricing approval), and Fresenius Medical Care agreed to use commercially reasonable efforts to obtain the corresponding pricing approval. For the rest of the world (i.e., outside the United States and the EU), once such criteria have been satisfied for the applicable country, or if the parties otherwise mutually agree to obtain regulatory and pricing approval for the distribution product in the field in the applicable country, Fresenius Medical Care agreed to use commercially reasonable efforts to obtain such approvals, and we agreed to use commercially reasonable efforts to support Fresenius Medical Care in its efforts.

Under the distribution agreement, we grant an exclusive, sublicensable license to Fresenius Medical Care under the patents, know-how and regulatory materials controlled by us during the term to commercialize the distribution product in the field outside the United States, subject to our retained rights to carry out our obligations under the distribution agreement. We also grant a non-exclusive, sublicensable license to Fresenius Medical Care under the patents, know-how and regulatory materials controlled by us during the term to develop the distribution product in accordance with the terms of the distribution agreement. In addition, we grant to Fresenius Medical Care, among other things, a perpetual, irrevocable, non-exclusive sublicensable license under the patents and know-how that primarily relate to the distribution product or its manufacture and that were created, conceived or developed solely or jointly by or on behalf of Fresenius Medical Care in the performance of its activities under the distribution agreement.

The distribution agreement provides that we will own all know-how and patents that primarily relate to the distribution product or its manufacture that are created, conceived or developed by or on behalf of either party in the performance of activities under the distribution agreement. Ownership of all other know-how, patents, materials and other intellectual property created, conceived or developed during the performance of activities under the distribution agreement will be determined in accordance with U.S. patent laws for determining inventorship.

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We are obligated to make payments to Fresenius Medical Care based on a share of aggregate net sales by or on behalf of us of the distribution product in the United States in the field. Such revenue-share payments will be a percentage of net sales in the low double digits, without regard to the calendar year in which such net sales are attributable, until such time that we have paid to Fresenius Medical Care a certain total amount, at which time the revenue-share will decrease to a percentage of net sales in the mid-single digits. The amounts that Fresenius Medical Care will be obligated to pay us under the distribution agreement for sales of the distribution product in the field outside of the United States will vary. Fresenius Medical Care agreed to pay us initially, on a country-by-country basis for sales outside of the United States, the amount equal to the average cost of manufacturing our distribution product plus a fixed dollar amount per unit. Following a specified period, on a country-by-country basis outside of the United States, Fresenius Medical Care will pay us a fixed percentage of net sales for each unit sold in such country, such that the Company will receive more than half of such net sales.

The distribution agreement will generally continue on a country-by-country basis until the later of the tenth anniversary of the launch date of the distribution product in the relevant country or (b) the expiration of the last-to-expire valid claim of specified patents in such country. Each party is permitted to terminate the distribution agreement for insolvency of, or, under certain circumstances, including various cure periods, material breach by the other party. Subject to a cure period, Fresenius Medical Care may also terminate the distribution agreement in its entirety or on a country-by-country basis (i) for certain withdrawals of regulatory approval or (ii) for termination or expiration of any of our in-licenses that is necessary for the exercise of Fresenius Medical Care’s rights, or the satisfaction of its obligations, under the distribution agreement. In addition, Fresenius Medical Care may terminate the distribution agreement for convenience on a country-by-country basis upon not less than 12 months’ written notice to us, although Fresenius Medical Care is not permitted to give such notice prior to the end of the second year following launch of the distribution product in such country. Each party is required to indemnify one another for certain third-party claims.

Third-Party Reimbursement

We anticipate that coverage and reimbursement by the Centers for Medicare and Medicaid Services (“CMS”) and private payors will be essential for most patients and health care providers to afford our treatments, particularly in the applications of renal replacement therapy for dialysis access and the treatment of PAD. Accordingly, sales of our products will depend substantially, both domestically and abroad, on reimbursement by government authorities, private health coverage insurers and other third-party payors. Our strategy around ATEV reimbursement focuses on achieving alignment and agreement from CMS on coding and payment pathways; both are critical to influencing and achieving optimal reimbursement payment from private payor sources. Therefore, Humacyte continues to develop a comprehensive reimbursement strategy including CMS, private payors, and other key stakeholders to ensure a clear and sustainable reimbursement path for all ATEV product opportunities.

We are pursuing a dual regulatory and legislative reimbursement strategy to ensure separate Medicare payment for the ATEV at an appropriate price. The regulatory strategy includes (1) engaging CMS political and career staff directly on coverage, payment, and coding followed by (2) submission of formal applications in these areas once FDA approval is obtained. Currently, no RMAT tissue engineered product has established coverage and reimbursement by CMS, and it is difficult to predict what CMS will decide with respect to coverage and reimbursement for fundamentally novel products. See “Risk Factors — Risks Related to the Development and Commercialization of Our Product Candidates” for further information. Even if we receive marketing approval for our ATEVs, there is uncertainty with respect to third-party coverage and reimbursement of our ATEVs. 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.

Containment of healthcare costs has been a priority of federal, state, and foreign governments, and the prices of drug products have been a focus of this effort. Governments have shown significant interest in implementing cost-containment programs. This interest has resulted in significant proposed and enacted reform measures affecting healthcare reimbursement and drug pricing, including the enactment in August 2022 of significant changes to potential Medicare drug product reimbursement through government negotiation of certain drug prices, as well as manufacturer discount and inflation rebate obligations under the Inflation Reduction Act (the “IRA”).

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Intellectual Property

We strive to protect and enhance the proprietary technology, inventions and improvements that are commercially important to the development of our business, including seeking, maintaining, and defending patent rights, whether developed internally or licensed from third parties. We also rely on trade secrets relating to our proprietary technology platform and on know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen and maintain our proprietary position that may be important for the development of our business. We additionally may rely on regulatory protection afforded through data exclusivity, market exclusivity and patent term extensions where available.

Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for commercially important technology, inventions and know-how related to our business, defend and enforce our patents, preserve the confidentiality of our trade secrets, and operate without infringing the valid and enforceable patents and proprietary rights of third parties.

As of December 31, 2025, our patent estate is comprised of 15 families of patents. Of these families, 11 are solely owned by Humacyte, one is jointly owned by Humacyte and Global Life Sciences Solutions USA LLC, one is jointly owned by Humacyte and Yale University, one is exclusively licensed to Humacyte from Duke University and one is exclusively licensed to Humacyte from Yale University. For more information regarding these license agreements, see “— License Agreement with Duke University” and “— License Agreements with Yale University.”

Our 15 families of patents are comprised of:

(i)
Eleven issued U.S. patents, 76 foreign patents in Austria, Australia, Belgium, Canada, China, Cyprus, Denmark, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Netherlands, Portugal, Spain, Sweden, Switzerland, Turkey, and the UK, eight pending U.S. non-provisional patent applications, and 15 pending foreign applications in Australia, Canada, China, Europe, Japan and Hong Kong, which are solely owned by us,

(ii)
four issued U.S. patents, 25 issued foreign patents in Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Portugal, Netherlands, Spain, Sweden, Switzerland, Turkey, and the UK, no pending U.S. non-provisional patent applications, and three pending foreign patent applications in Europe and Canada, which we co-own, and

(iii)
two issued U.S. patent, two issued foreign patents in Australia and Japan, one pending U.S. non-provisional patent application, and three pending foreign patent applications in Canada, Europe, and Hong Kong, which we exclusively license.

Many of these patents and patent applications generally relate to the scaffolds used to make Symvess and our product candidates, the composition of Symvess and our product candidates, and systems and methods of manufacturing Symvess and our product candidates. Excluding any patent term adjustment or patent term extension, the U.S. patent relating to the scaffold used to make Symvess and our product candidates expires in 2032, the U.S. patents relating to the composition of our vessels expire in 2032 and the U.S. patents relating to the systems and methods of manufacturing Symvess and our product candidates expires in 2032. Based on the FDA approval of the ATEV in December 2024, in February 2025 we filed with the U.S. Patent and Trademark Office an application for extension of patent term on one of our U.S. patents relating to the composition of Symvess and our product candidates under 35 U.S.C. § 156. If granted, we estimate that the expiration of the patent will be extended by approximately 50 months. The U.S. patent relating to the entangler machinery used to make tubular scaffolds expires in 2035. Included in our patent portfolio is one U.S. patent expiring in 2040, and multiple pending, Humacyte-owned non-provisional applications relating to the manufacturing of engineered tissues at commercial scale, as well as other technologies and product candidates. If these non-provisional applications are allowed, such additional patents issuing therefrom would be expected to expire around 2043.

As with other biotechnology and pharmaceutical companies, our ability to maintain and solidify our proprietary and intellectual property position for our product candidates will depend on our success in obtaining effective patent claims and enforcing those claims if granted. However, our owned and licensed pending patent applications, and any patent applications that

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we may in the future file or license from third parties, may not result in the issuance of patents. For more information, see “Risk Factors — Risks Related to Our Intellectual Property.”

We have also registered trademarks for use in connection with our products. These include registrations for Symvess® in the United States and pending registrations for Symvess in Europe, United Kingdom and Ukraine, HUMACYL™ in the United States, Europe, Australia, Canada, China, and Israel; HUMAGRAFT™ in Australia, China, Europe, and Israel; HUMAPASS™ in Europe, Australia, and Israel; HUMACYTE in the United States, Europe, Australia, Canada, and Israel; and, BVP™ in the United States. We may pursue additional registrations for future products in markets of interest.

In addition to the above, we have established expertise and development capabilities focused in the areas of preclinical research and development, manufacturing process scale-up, cGMP manufacturing, quality control, quality assurance, compliance, regulatory affairs and clinical trial design and execution. We believe that our focus and expertise will help us develop and expand technology-based applications leveraging our proprietary intellectual property.

Finally, we rely, in some circumstances, on trade secrets to protect our technology. We seek to protect our proprietary technology and processes, in part, by entering into confidentiality agreements with our employees, consultants, scientific advisors and contractors. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems.

In addition to the intellectual property that we have developed internally, we license rights to certain intellectual property that is material to our business prospects. We have summarized our material license agreements below.

License Agreement with Duke University

In March 2006, we entered into a license agreement with Duke University (“Duke”), which was subsequently amended in 2011, 2014, 2015, 2018, 2019 and January 2022 (as amended, the “Duke License Agreement”). Under the Duke License Agreement, Duke granted us a worldwide, exclusive, sublicensable license to certain patents related to decellularized tissue engineering, which we refer to as the patent rights, as well as a non-exclusive license to use and practice certain know-how related to the patent rights. The relevant licensed patent on decellularization of tissue expired in 2021. We have agreed to use commercially reasonable efforts to develop, register, market and sell products utilizing the patent rights, which we refer to as the licensed products. Any services provided to a third party utilizing licensed products are referred to as licensed services. We have also agreed to meet certain benchmarks in our development efforts, including as to development events, clinical trials, regulatory submissions and marketing approval, within specified timeframes. Under the Duke License Agreement, Duke retains the right to use the patent rights for its own educational and research purposes, and to provide the patent rights to other non-profit, governmental or higher-learning institutions for non-commercial purposes without paying royalties or other fees.

In connection with our entry into the Duke License Agreement, we granted equity consideration to Duke in the form of 52,693 shares of our post-Merger common stock. Under the Duke License Agreement, we have also agreed to pay Duke: a low single-digit percentage royalty on eligible sales of licensed products and licensed services, plus a low double-digit percentage of any sublicensing revenue; an annual minimum royalty beginning in 2012, which increased in the calendar year immediately following the first commercial sale of licensed products or licensed services (whichever occurs first); and an additional amount in license fees, as certain scientific milestones are met.

The Duke License Agreement remains effective until the latter of (i) the last of the patent rights expires or (ii) four years after our first commercial sale, unless earlier terminated. Either party may terminate the agreement for fraud, willful misconduct or illegal conduct, or uncured material breach. Duke may terminate the agreement if we become insolvent. Duke may also terminate the license, convert the license into a non-exclusive license or seek assignment of any sublicense if we fail to reach diligence milestones within the applicable time period. If we abandon any claim, patent or patent application, our rights under the license with respect to such patent rights will be terminated in the territory in which we abandon such rights. We may terminate the Duke License Agreement unilaterally upon three months’ prior notice to Duke. We agree to indemnify Duke against certain third-party claims.

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License Agreements with Yale University

Large Diameter ATEV

In August 2019, we entered into a license agreement with Yale University (“Yale”) that granted us a worldwide license to the patents jointly owned with us related to tubular prostheses which are large diameter versions of our ATEVs, which may or may not contain a stent (the “Tubular Prothesis License Agreement”). The license granted under the Tubular Prothesis License Agreement is exclusive in the field of engineered urinary conduits, engineered tracheae/airways and engineered esophagi, except that it is subject to Yale’s non-exclusive right, on behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes. We have agreed to use reasonable commercial efforts to develop and commercialize the licensed patents and any licensed products and methods, and to use reasonable efforts to make the licensed products available to patients in low and low-middle income countries. We are also obligated to provide Yale periodically an updated and revised copy of our plan, which must indicate progress of our development and commercialization. We may also sublicense our rights without Yale’s prior written consent, but such sublicense is subject to certain conditions.

In connection with our entry into the Tubular Prothesis License Agreement, we paid Yale an upfront cash fee of less than $0.1 million. We have also agreed to pay to Yale: an annual maintenance fee, increasing between the first anniversary of the agreement until the fifth anniversary up to a maximum of less than $0.1 million per year; milestone payments upon achievement of certain regulatory and commercial milestones of $0.2 million and $0.6 million for this license; a low single-digit percentage royalty on worldwide net sales, subject to reductions for third-party license fees; and a low double-digit percentage of sublicensing income.

If we or any of our future sublicensees bring a patent challenge against Yale or assist another party in bringing a patent challenge against Yale, the license fees described above will be subject to certain increases and penalties.

The Tubular Prothesis License Agreement expires on a country-by-country basis on the date on which the last of the patents in such country expires, lapses or is declared invalid. Issued patents and additional patents issuing from this licensed portfolio will expire no earlier than 2032, and the term of each patent may be extended by patent term adjustment, patent term extension, or foreign equivalents thereof. Issued U.S. patent No. 10,172,707 will expire no earlier than 2035. Issued patents and additional patents issuing from this licensed portfolio will expire no earlier than 2032, and the term of each patent may be extended by patent term adjustment, patent term extension, or foreign equivalents thereof. Issued U.S. patent No. 10,172,707 will expire no earlier than 2035. Yale may terminate the Tubular Prothesis License Agreement if we fail to (i) provide written diligence reports, (ii) provide a commercially reasonable diligence plan, (iii) implement the plan in accordance with the obligations under the agreement, or (iv) reach certain research and development milestones within the scheduled timeframe set forth in the agreement; however, any such termination right would be limited in scope to the country or countries to which such failure relates. Yale may also terminate for our non-payment, uncured material breach, failure to obtain adequate insurance, bringing or assisting in bringing of a patent challenge against Yale, abandonment of the research and development of our product or insolvency. We may terminate the Tubular Prothesis License Agreement (i) on 90 days’ prior written notice to Yale, provided we are not in breach of the license agreement and have made all required payments to Yale thereunder and (ii) on written notice to Yale following an uncured material breach. Under certain circumstances, Yale may, at its option, convert the exclusive license to a non-exclusive license if we decline to initiate certain infringement or interference proceedings with respect to the licensed patents. We have agreed to indemnify Yale against certain third-party claims.

BioVascular Pancreas

In August 2019, we entered into a license agreement with Yale that granted us a worldwide license to its patents related to a BVP (the “BVP License Agreement”). The license granted under the BVP License Agreement is exclusive in the field of acellular vascular tissues that deliver pancreatic islet cells to patients, except that it is subject to Yale’s non-exclusive right, on behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes. We have agreed to use reasonable commercial efforts to develop and commercialize the licensed patents and any licensed products and methods, and to use reasonable efforts to make the licensed products available to patients in low

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and low-middle income countries. We are also obligated to provide Yale periodically an updated and revised copy of our plan, which must indicate progress of our development and commercialization. We may also sublicense our rights without Yale’s prior written consent, but such sublicense is subject to certain conditions.

In connection with our entry into the BVP License Agreement, we paid Yale an upfront cash fee of less than $0.1 million. We have also agreed to pay to Yale: an annual maintenance fee, increasing between the first anniversary of the agreement until the fifth anniversary up to a maximum of less than $0.1 million per year; milestone payments upon achievement of certain regulatory and commercial milestones of $0.1 million and $0.2 million for this license; a low single-digit percentage royalty on worldwide net sales, subject to reductions for third-party license fees; and a low double-digit percentage of sublicensing income.

If we or any future sublicensees bring a patent challenge against Yale or assist another party in bringing a patent challenge against Yale, the license fees described above will be subject to certain increases and penalties.

The BVP License Agreement expires on a country-by-country basis on the date on which the last of the patents in such country expires, lapses or is declared invalid. Patents issuing from this licensed portfolio will expire no earlier than 2039, and the term of each patent may be extended by patent term adjustment, patent term extension, or foreign equivalents thereof. Patents issuing from this licensed portfolio will expire no earlier than 2039, and the term of each patent may be extended by patent term adjustment, patent term extension, or foreign equivalents thereof. Yale may terminate the BVP License Agreement if we fail to (i) provide written diligence reports, (ii) provide a commercially reasonable diligence plan, (iii) implement the plan in accordance with the obligations under the agreement, or (iv) reach certain research and development milestones within the scheduled timeframe set forth in the agreement; however, any such termination right would be limited in scope to the country or countries to which such failure relates. Yale may also terminate for our non-payment, uncured material breach, failure to obtain adequate insurance, bringing or assisting in bringing of a patent challenge against Yale, abandonment of the research and development of our product or insolvency. We may terminate the BVP License Agreement (i) on 90 days’ prior written notice to Yale, provided we are not in breach of the license agreement and have made all required payments to Yale thereunder and on written notice to Yale following an uncured material breach. Our rights under the BVP License Agreement will also terminate automatically with respect to a patent application or patent within the licensed patents in a specified country if, upon receipt of written notice from Yale, we do not agree to pay the patent filing, prosecution and maintenance fees incurred by Yale for such patent applications or patents in the specified country. Under certain circumstances, Yale may, at its option, convert the exclusive license to a non-exclusive license if we decline to initiate certain infringement or interference proceedings with respect to the licensed patents. We have agreed to indemnify Yale against certain third-party claims.

Competition

Despite the magnitude and critical nature of the diseases and conditions we are targeting, no significant advances in the open surgical market have been made in the last 35 years, and current treatment and products used in vascular repair, reconstruction and replacement suffer from various drawbacks. The large majority of vascular repair, reconstruction and replacement procedures rely on either harvesting autologous veins or using synthetic grafts. However, each method presents significant limitations as discussed below:

Autologous Veins

The harvest of autologous veins is a serious operation that can result in numerous complications, including infection, chronic pain, and limb swelling that severely impact the patient’s quality of life. In addition, this procedure can often result in long recovery times, increased hospital stays, and increased risk of hospital readmission. In order to obtain an autologous vein, such as a saphenous vein, for use in a surgical procedure, a second operation must be performed on the patient to harvest the vein. The harvesting process must be completed before the bypass procedure occurs and can take significant time to complete, which increases costs related to the additional operative time and staff required to perform the operation. Even if successful, the patient’s recovery time could increase as the patient must recover from two surgical procedures instead of one, further increasing morbidity and cost. Additionally, a significant percentage of patients are not suitable for vein harvesting either due to vein or limb damage, limited vein supply from prior harvest, venous disease or the surgeon’s desire to preserve the vein for future coronary or other bypass procedures. In acute trauma, the time to restore blood flow to injured limbs is delayed when a vein must

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be harvested from the patient, which puts the limbs at greater risk of reduced function or amputation. For patients suffering from vascular trauma, some types of injury preclude the harvesting of autologous saphenous vein due to concomitant injuries of one or both legs. Furthermore, time is required to prepare the vein harvest site and to remove the vein from the leg, which adds to ischemia time and can increase the risk of tissue and limb loss. Rates of traumatic limb loss are strongly tied to ischemia time, and therefore rapid revascularization using an off-the-shelf ATEV conduit may decrease ischemia time and lead to better outcomes.

The use of autologous vein for creating an AV fistula for use in hemodialysis is often limited by vein size and location. The vast majority of veins must go through a process of enlargement, known as maturation, prior to use for hemodialysis. For approximately 40% of patients receiving fistulae, the vein does not mature sufficiently to allow for hemodialysis even after six months. Even in patients having adequate veins for fistula creation, the fistula often becomes large, tortuous and disfiguring and can be at risk for sometimes fatal rupture.

Synthetic Grafts

Use of synthetic materials, such as ePTFE and Dacron, while widely available, have known complications, such as continuous chronic risk of infection and clotting inside the graft. Risk of infection is significantly increased in acute battlefield and civilian injuries, as well as in contaminated wounds. The body recognizes any synthetic materials as foreign and, therefore, can mount a host foreign body response following implantation. Synthetic materials also have been shown to be inferior to autologous vein in resisting infection, and generally only are used for vascular repair when autologous vein is not an option.

In hemodialysis access, persistent puncture presents an ongoing risk of graft infection. The annual risk of infection of ePTFE grafts in hemodialysis patients can be as high as 10% – 15% per patient-year. Furthermore, gradual degradation of the non-healing ePTFE graft material caused by persistent needle punctures can eventually lead to graft failure. In traumatic vascular injury, ePTFE grafts are generally contraindicated, due to the high rates of contamination of the wound that can lead to synthetic graft infection and failure.

Two lesser used products, cryopreserved human blood vessels, known as allografts, and animal-derived vessels, known as xenografts, also involve significant limitations.

Cryopreserved Blood Vessels

To eliminate the need for harvesting autologous vein, some surgeons use allogeneic vessels that have been previously harvested from cadavers and cryogenically preserved. These allogeneic vessels are stored at -80 degrees Celsius and must be thawed prior to use, which can take up to 60 minutes. The supply of cryopreserved vessels is limited by the number of cadaveric donors available, and the vessels are often non-uniform in size. In addition, because the vessels contain human cells from a donor, they can generate an immune rejection response that can lead to aneurismal degradation or catastrophic failure. Furthermore, development of antibodies to the implanted cryopreserved human vessel frequently has a detrimental impact on the ability of the patient to receive a transplant in the future. Cryopreserved blood vessels are only rarely used in the treatment of vascular trauma, due to the time required for procurement and thawing, and the high rates of rejection response.

Animal-Derived Vessels

Xenogeneic tissues, including cow, pig or sheep-derived vessels, are used less frequently in vascular surgery, in part due to the risk of thrombosis and structural deterioration over time. The limited clinical data that are available for existing xenografts in vascular reconstruction indicates lower patency rates and higher incidence of complications when compared to autologous vein. Xenografts are all chemically treated in efforts to minimize rejection to animal components, and therefore do not respond like living tissue. Some of these products require rinsing to remove toxic chemicals used for storage.

Our Solution

We believe our ATEVs combine the off-the-shelf availability of synthetic grafts with the regenerative capabilities of autologous vessels. We believe these and other attributes have the potential to address unmet clinical needs in a range of disease

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states, including atherosclerosis, end-stage kidney disease, coronary artery disease, vascular trauma, pediatric congenital heart disease, airway disease, and others. We believe that the ATEVs multiple key characteristics will drive rapid clinical adoption amongst surgeons and the broader healthcare community:

•
Off-the-Shelf: Our “cabinet” of ATEVs of varying diameters and lengths is designed to be stored on-site at facilities such as hospitals, trauma centers and outpatient surgical centers.

•
Immediately Available: When needed, our ATEVs are available for immediate use by opening and removing the ATEV from its original flexible bioreactor bag. Since our ATEV does not need flushing, harvesting or thawing, as is common with other vascular substitute alternatives, we believe hospitals will be able to use our ATEVs for vascular surgery more quickly with smaller surgical teams, reduced logistics and decreased overall cost.

•
No Surgical Harvesting: The use of our ATEVs does not subject patients to the serious operation of harvesting an autologous vein, which can result in greater procedure and recovery time, potential scarring and disfigurement, increased costs, and numerous potential health complications.

•
Non-Immunogenic and No Foreign Body Response: Given their acellular nature, our ATEVs have the potential to be universally implantable and durable across patients. Because our ATEVs are derived from human tissue (but cleansed of all cells and cellular components), we believe (and have observed in clinical trials to date) that they do not generate the foreign body response associated with the use of synthetic grafts, or the immune response associated with cryopreserved vessels.

•
Low Infection Susceptibility: In clinical trials to date, we have observed reduced rates of infection in our ATEVs as compared to synthetic materials. As a result, we believe our ATEVs may be used in complicated and potentially contaminated wounds with fewer patient complications following the initial procedure.

•
Uniform and Predictable Size, Structure and Quality: Harvested veins vary in size, structure and quality by donor. We manufacture our ATEVs to precise specifications under controlled quality standards, which will allow surgeons the flexibility to quickly and easily select an ATEV in the appropriate size and shape for each indication.

•
Regenerative Potential: Our ATEVs repopulate with the patient’s own vascular cells, creating a living vascular tissue with the associated long-term benefits of self-healing and infection resistance.

We expect our ATEVs will compete with the use of a patient’s own blood vessels, as well as a variety of marketed products, such as conventional synthetic grafts, xenografts, and allografts, as well as developing technologies. We expect the key competitive factors affecting the commercial success of our ATEVs to likely be efficacy, safety, convenience, pricing and reimbursement.

Other Commercial Entities

There are several conventional synthetic grafts made of ePTFE or Dacron presently on the market from companies such as Bard Peripheral Vascular, Inc., W.L. Gore & Associates, Inc., Terumo Medical Systems, and Atrium (Maquet Getinge Group) that are used for both AV access for hemodialysis and vascular repair. Xenograft and allograft products are also available, but not widely used. Xenografts, such as Artegraft® and Procol®, are processed animal-derived vessels, while allografts are processed allogeneic cellular vessels, such as CryoVein® and AngioGRAFT®.

There are also a number of companies of which we are aware that have preclinical and early clinical-stage research programs underway to develop products that could potentially compete with our ATEVs, including NovaHep AB, Xeltis AG, Hancock Jaffe, and Vascudyne Inc. We may face competition from these and other emerging technologies such as bioabsorbable polymetric implants and electrospun or 3D printed tubular conduits.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are more effective, safer, have fewer or less severe side effects, are more convenient or are less expensive than the products that we

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develop. Our competitors also may obtain FDA or other marketing approval for their products more rapidly than we may obtain the same approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market.

Government Regulation

Overview

The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements on the research, development, testing, manufacture, quality control, safety, effectiveness, packaging, labeling, storage, record keeping, marketing, advertising and promotion, import/export, and distribution of Symvess and our product candidates.

In the United States, the FDA regulates pharmaceutical drugs, medical devices and biologic products under the Federal Food, Drug, and Cosmetic Act (“FDCA”), the Public Health Service Act (“PHSA”), FDA implementing regulations, and other laws. Symvess and our product candidates are subject to regulation by the FDA as biologics. Biologics require the submission of a BLA and approval by the FDA before being marketed in the United States. Our first vessel product, Symvess, received approval of its BLA on December 19, 2024 for use 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. None of our other vessel products or other investigational products have received FDA approval. If we fail to comply with applicable FDA or other requirements at any time during the product development process, clinical testing, and the approval process or after approval, we may become subject to administrative or judicial sanctions. These sanctions could include the FDA’s refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties or criminal prosecution. Any FDA enforcement action could have a material adverse effect on us.

Marketing Approval — Biological Products in the United States

Before a biologic is approved in the United States, an applicant must submit a BLA that includes sufficient evidence to establish the safety, purity, and potency of the product candidate for its intended indications, including from the results of preclinical studies and clinical trials. A BLA must also contain extensive information about manufacturing and product quality control testing, and the applicant must pass an FDA preapproval inspection of the manufacturing facility or facilities at which the biologic product is produced and distributed from to assess compliance with current good manufacturing practices (“cGMPs”).

The steps for obtaining FDA approval of a BLA to market a biologic product in the United States generally include:

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Completion of extensive preclinical laboratory tests and preclinical animal studies performed in accordance with the FDA’s current good laboratory practice (“GLP”) regulations;

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

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Approval of the protocol and related documentation by an Institutional Review Board (“IRB”) or ethics committee representing each clinical site before each clinical trial may be initiated;

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Performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as GCPs and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the product candidate for each proposed indication;

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Submission to the FDA of a BLA;

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Satisfactory completion of an FDA inspection of the manufacturing facility or facilities and distribution site at which the product is produced: to assess compliance with cGMP regulations; to assure that the facilities, production methods,

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testing and controls are adequate; and, if applicable, to assure compliance with current good tissue practice (“cGTP”) requirements for human cellular and tissue-derived products;

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Potential FDA audit of the nonclinical study and clinical trial sites that generated the data in support of the BLA;

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Review of the product candidate by an FDA advisory committee, if applicable;

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Payment of user fees for FDA review of the BLA (unless a fee waiver applies); and

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FDA review and approval, or licensure, of the BLA prior to any commercial marketing, sale or shipment of the product.

U.S. Biological Products Development Process

The testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any further approvals for Symvess and/or our product candidates will be granted on a timely basis, if at all.

Once a product candidate is identified for development, that biologic candidate enters the preclinical testing stage. Preclinical studies include laboratory evaluations of product chemistry, toxicity, formulation and stability, as well as animal studies to evaluate the product’s potential safety and activity. The results of the preclinical studies, together with manufacturing information, analytical data, and at least one protocol for clinical study, are submitted to the FDA as part of an IND. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises concerns or questions about the conduct of the clinical trial, including concerns that human research subjects will be exposed to unreasonable health risks. This is known as a “clinical hold.” In such a case, the IND sponsor must resolve all of the FDA’s concerns to the agency’s satisfaction before the clinical trial can begin. Submission of an IND may result in the FDA not allowing the clinical trials to commence or not allowing the clinical trials to commence on the terms originally specified in the IND. A separate submission to an existing IND must also be made for each successive clinical trial conducted during product development, and the FDA must grant permission, either explicitly or implicitly by not objecting, before each clinical trial can begin. Even after a clinical trial has begun, the FDA can issue a clinical hold at any time if it concludes that certain conditions exist, such as patients may be exposed to an unreasonable and significant risk of illness or injury.

Clinical trials involve the use of the product candidate in human subjects under the supervision of qualified investigators. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be used. Each protocol must be submitted to the FDA as part of the IND. An independent IRB for each medical center proposing to conduct a clinical trial must also review and approve a plan for any clinical trial before it can begin at that center and the IRB must monitor the clinical trial until it is completed. The IRB must review and approve, among other things, the study protocol and informed consent information to be provided to study subjects. Some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee. This group provides authorization as to whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the study. Clinical testing also must satisfy extensive GCP requirements, including the requirements for informed consent. Information about clinical trials must be submitted within specific timeframes to the National Institutes of Health (“NIH”) for public dissemination on its ClinicalTrials.gov website.

For purposes of BLA submission and approval, clinical trials are typically, though not always, conducted in three sequential phases, which may overlap or be combined. For certain of Humacyte’s development of product candidates, Phase 1 and Phase 2 trials have heretofore been combined into a single trial design.

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Phase 1. The biological product is initially introduced into human subjects and tested for safety. These initial trials to evaluate the potential toxicity and pharmacological activity of the investigational product (including pharmacokinetics, if applicable), and, if possible, gain early evidence on effectiveness.

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Phase 2. The biological product is evaluated in a limited patient population to identify potential adverse events and safety risks, to evaluate preliminarily the efficacy of the product candidate for specific targeted indications in patients with the disease or condition under trial, and, when applicable, to evaluate dosage tolerance and appropriate dosage.

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Phase 3. The biological product is administered to an expanded patient population, often large numbers of patients of several hundred to several thousand and generally at geographically dispersed clinical trial sites. These trials are designed to generate enough data to statistically evaluate clinical effectiveness and safety as well as to establish the overall benefit-risk relationship of the investigational new biological product, and to provide an adequate basis for product approval. FDA typically requires at least two Phase 3 trials to support approval, but in some cases may approve an application on the basis of one trial. For example, FDA’s approval of our BLA for Symvess for extremity arterial injury was based on a single pivotal trial with supporting evidence from humanitarian use of the product in Ukraine.

In some cases, the FDA may condition approval of a BLA on the sponsor’s agreement to conduct additional clinical trials to further assess the biologic’s safety and effectiveness after BLA approval. Such post-approval clinical trials are typically referred to as Phase 4 clinical trials.

During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical trial investigators. Annual progress reports detailing the progress of the clinical trials must be submitted to the FDA. Written IND safety reports must be promptly submitted to the FDA and the investigators detailing serious and unexpected adverse events, any findings from other studies that suggest a significant risk to human patients, tests in laboratory animals or in vitro testing that suggest a significant risk for human patients, or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.

The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research patients are being exposed to an unacceptable health risk, including risks inferred from other trials on other products. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biological product has been associated with unexpected serious harm to patients.

Concurrent with clinical trials, companies usually complete additional animal trials and must also develop additional information about the characteristics of the biologic and finalize a process for manufacturing the biologic in commercial quantities in accordance with cGMP and, when applicable, GTP requirements. The manufacturing process must be capable of consistently producing quality batches of the product candidate. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

BLA Review Process

The results of preclinical studies and of the clinical trials, together with other detailed information, including extensive manufacturing information, information on the composition of the biologic, and proposed labeling, are submitted to the FDA in the form of a BLA requesting approval to market the biologic in the United States for one or more specified indications. The FDA reviews a BLA to determine, among other things, whether a biologic is safe and effective for its intended use.

The FDA has 60 days from its receipt of a BLA to determine whether the application will be accepted for filing based on the FDA’s threshold determination that the application is sufficiently complete to permit substantive review. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information. In this event, the BLA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. After the BLA submission is accepted for filing, the FDA reviews the BLA to determine, among other things, whether the proposed product is safe and potent, or effective, for its intended use, and has an

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acceptable purity profile, and whether the product is being manufactured in accordance with cGMPs (and, where applicable, GTPs) to assure and preserve the product’s identity, safety, strength, quality, potency, and purity, and biological product standards. The FDA may refer applications for novel biological products or biological products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes outside clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and, if so, under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

Before approving an application, the FDA will, among other things, inspect the facility or the facilities at which the biologic product is manufactured and distributed, and will not approve the product unless cGMP compliance is satisfactory. The FDA may also inspect the sites at which the clinical trials were conducted to assess their compliance, and may refuse to approve the biologic if compliance with GCP requirements is found to be unsatisfactory. For a human cellular or tissue product the FDA also may refuse to approve the product if the manufacturer is not in compliance with GTP requirements, in addition to cGMPs.

The FDA also has authority to require a Risk Evaluation and Mitigation Strategy (“REMS”) from manufacturers to ensure that the benefits of a biological product outweigh its risks. A sponsor may also voluntarily propose a REMS as part of the BLA submission. The need for a REMS is determined as part of the review of the BLA. Based on statutory standards, elements of a REMS may include “dear doctor letters,” a medication guide, more elaborate targeted educational programs, and in some cases restrictions on distribution and/or use. These elements are negotiated as part of the BLA approval, and in some cases may delay the approval date. Once adopted, REMS are subject to periodic assessment and modification.

The testing and approval processes require substantial time, effort and financial resources, and each may take several years to complete. The FDA may not grant approval on a timely basis, or at all. Even if we believe a clinical trial has demonstrated safety and efficacy of one of our product candidates for the treatment of a disease, the results may not be satisfactory to the FDA. Preclinical and clinical data may be interpreted by the FDA in different ways, which could delay, limit or prevent regulatory approval. We may encounter difficulties or unanticipated costs in our efforts to secure necessary governmental approvals, which could delay or preclude us from marketing new indications for Symvess and/or our product candidates. The FDA may limit the indications for use or place other conditions on any approvals that could restrict the commercial application of the products.

Biologics may be marketed only for the FDA approved indications and in accordance with the provisions of the approved labeling. Further, if there are any modifications to the biologic, including changes in indications, labeling, or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new BLA or BLA supplement, which may require developing additional data or conducting additional preclinical studies and clinical trials. As with new BLAs, the review process is often significantly extended by FDA requests for additional information or clarification.

The Biologics Price Competition and Innovation Act (“BPCIA”), amended the PHSA to authorize the FDA to approve similar versions of innovative biologics, commonly known as biosimilars. A competitor seeking approval of a biosimilar must file an application to establish its product as highly similar to an approved innovator biologic, among other requirements. The BPCIA, however, bars the FDA from approving biosimilar applications for 12 years after an innovator biological product receives initial marketing approval. This bar does not apply to submission or approval of full BLAs. Because Symvess received its initial approval for marketing via a BLA, we believe that it will be entitled to 12 years of exclusivity. Nevertheless, the BPCIA is complex and is only beginning to be interpreted and implemented by the FDA. As a result, its ultimate impact, implementation and meaning is subject to uncertainty.

Expedited Development and Review Programs

The FDA offers various programs, including Fast Track designation, Breakthrough Therapy Designation, accelerated approval, priority review and RMAT designation, that are intended to expedite the process for the development and FDA review of biological products that are intended for the treatment of serious or life-threatening diseases or conditions. To be eligible for Fast Track designation, biological product candidates must be intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. Fast Track designation applies to the combination of the product and the specific indication for which it is being studied. The sponsor of a biological product

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candidate may request the FDA to designate the biologic as a Fast Track product at any time during the clinical development of the product. The sponsor of a Fast Track product has opportunities for more frequent interactions with the applicable FDA review team during product development and, once a BLA is submitted, the product candidate may be eligible for priority review. A Fast Track product may also be eligible for rolling review, where the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.

A biological product candidate may be eligible for Breakthrough Therapy Designation if it is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Breakthrough Therapy Designation provides all the features of Fast Track designation in addition to intensive guidance on an efficient development program beginning as early as Phase 1, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where appropriate.

Any marketing application for a biological product submitted to the FDA for approval, including a product candidate with a Fast Track designation and/or Breakthrough Therapy Designation, may be eligible for other types of FDA programs intended to expedite the FDA review and approval process, such as priority review and accelerated approval. Any product candidate is eligible for priority review if it is designed to treat a serious or life-threatening disease or condition, and if approved, would provide a significant improvement in safety or effectiveness compared to available alternatives for such disease or condition. The FDA will attempt to direct additional resources to the evaluation of an application for a biological product candidate designated for priority review in an effort to facilitate the review. Under priority review, the FDA’s goal is to review an application within six months of the 60-day filing date, compared to ten months for a standard review.

Additionally, FDA may grant accelerated approval to a product candidate intended to treat a serious or life-threatening disease or condition upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a condition of approval, the FDA may require that a sponsor of a biological product receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials to verify and describe the anticipated effect on irreversible morbidity or mortality or other clinical benefit. Products receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails to conduct the required post-marketing studies or if such studies fail to verify the predicted clinical benefit. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

In 2017, the FDA established a new RMAT designation as part of its implementation of the 21st Century Cures Act. The RMAT designation program is intended to fulfill the 21st Century Cures Act requirement that the FDA facilitate an efficient development program for, and expedite review of, any biological product that meets the following criteria: (i) the biological product qualifies as an RMAT, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, with limited exceptions; (ii) the biological product is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and preliminary clinical evidence indicates that the biological product has the potential to address unmet medical needs for such a disease or condition. RMAT designation provides all the benefits of Breakthrough Therapy Designation, including more frequent meetings with the FDA to discuss the development plan for the product candidate and eligibility for rolling review and priority review. Product candidates granted RMAT designation may also be eligible for accelerated approval on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of clinical trial sites, including through expansion of trials to additional sites.

Fast Track designation, Breakthrough Therapy Designation, priority review, accelerated approval, and RMAT designation do not change the standards for approval but may expedite the development or approval process. Even if a product candidate

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qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Additionally, on December 12, 2017, Public Law No. 115-92 amended the FDCA to, among other things, allow the DoD to request, and FDA to provide assistance to expedite development and the FDA’s review of products to diagnose, prevent, treat or mitigate a specific and life-threatening risk to the U.S. military. Similar to the designations described above that FDA may grant, a priority designation by the DoD does not change the standards for approval but may expedite the development or approval process.

Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a biological product intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a biological product available in the United States for this type of disease or condition will be recovered from sales of the product. Orphan product designation must be requested before submitting a BLA. After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

Orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biological product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity, or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated. Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.

A designated orphan drug many not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation. In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if a second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Other U.S. Regulatory Requirements

For biologics that are human cells, tissues, and cellular and tissue-based products (“HTC/Ps”), manufacturers must also comply with the FDA’s HCT/P regulations at 21 C.F.R. Part 1271. These regulations impose a variety of specialized requirements as follows:

HCT/P registration and listing. Every establishment that manufactures an HCT/P must register with the FDA and provide a list of every HCT/P that the establishment manufactures. The definition of manufacture is broad and includes any and all steps in the recovery, processing, storage, labeling, packaging or distribution of any human cell or tissue and the screening or testing of the cell or tissue donor.

Donor eligibility. HCT/P manufacturers must maintain procedures for testing, screening and determining the eligibility of donors of cells and tissues used in HCT/Ps. An HCT/P may not be transferred or implanted into an individual until the donor has been determined to be eligible under these procedures. These procedures must involve, among other things, testing donors for certain communicable diseases and the use of quarantines for HCT/Ps that have not yet been shown to meet the eligibility requirements. Manufacturers must keep detailed records regarding donor eligibility determinations.

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Current Good Tissue Practices. HCT/Ps must be recovered, processed, stored, labeled, packaged and distributed in a manner that is consistent with the FDA’s cGTP regulations. Cells and tissues must also be screened and tested according to these regulations. The goal of cGTPs is to prevent the introduction, transmission or spread of communicable diseases. The FDA’s cGTPs regulations require companies to establish a comprehensive quality program and to comply with rules related to personnel, facilities and equipment used to manufacture HCT/Ps, as well as rules on how these HCT/Ps are processed, labeled and stored. Companies must also keep detailed manufacturing records and product complaint files.

Adverse Reaction Reports. Manufacturers of nonreproductive HCT/Ps must investigate and report to the FDA certain adverse reactions.

Inspections. Establishments that manufacture HCT/Ps must allow the FDA to inspect the establishment and company records.

Post-Approval Requirements

Any biologics manufactured or distributed by us or our collaborators pursuant to FDA approvals, such as Symvess, are subject to continuing post-approval regulation by the FDA, including recordkeeping requirements and reporting of adverse experiences associated with the product, as well as any post-marketing surveillance requested by the FDA as a condition to BLA approval. As a condition of approval of our BLA for Symvess in extremity arterial injury, we are obligated to conduct post-approval studies and trials, and report the results to the FDA. Manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMPs, which impose certain procedural and documentation requirements upon us and our third-party manufacturers. Failure to comply with the statutory and regulatory requirements can subject a manufacturer to possible legal or regulatory action, such as warning letters, suspension of manufacturing, seizure of product, injunctive action or possible civil penalties. We cannot be certain that we or our present or future third-party manufacturers or suppliers will be able to comply with the cGMP regulations and other ongoing FDA regulatory requirements. If we or our present or future third-party manufacturers or suppliers are not able to comply with these requirements, the FDA may halt our clinical trials, require us to recall our product from distribution or withdraw approval of the BLA for that product.

The FDA closely regulates the post-approval marketing and promotion of biologics to healthcare professionals, including standards and regulations for direct-to-consumer advertising, false or misleading claims, off-label promotion, industry-sponsored scientific and educational activities, and promotional activities involving the Internet. Failure to comply with these requirements can result in adverse publicity, warning letters, corrective advertising, and potential civil and criminal penalties. Physicians may prescribe legally available biologics for uses that are not described in the product’s labelling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, impose stringent restrictions on manufacturers’ communications regarding off-label use.

U.S. Healthcare Reform

Political, economic and regulatory influences are subjecting the healthcare industry in the United States to fundamental changes. There have been, and we expect there will continue to be, legislative and regulatory proposals to significantly change the healthcare system. For example, the Patient Protection and Affordable Care Act (the “ACA”) was enacted to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms. In December 2017, portions of the ACA dealing with the individual mandate insurance requirement were effectively repealed by the Tax Cuts and Jobs Act of 2017.

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U.S. Third-Party Payor Coverage and Reimbursement

The commercial success of Symvess and our product candidates, if they are approved for marketing, will depend, in part, upon the availability of coverage and reimbursement from third-party payors at the federal, state and private levels. Government payor programs, including Medicare and Medicaid, private health care insurance companies and managed-care plans have attempted to control costs by limiting coverage and the amount of reimbursement for particular procedures or treatments. The U.S. Congress and state legislatures from time to time propose and adopt initiatives aimed at cost-containment. Ongoing federal and state government initiatives directed at lowering the total cost of health care will likely continue to focus on health care reform and on the reform of the Medicare and Medicaid payment systems. Examples of how limits on coverage and reimbursement in the United States may cause reduced payments for products in the future include: changing Medicare reimbursement methodologies; fluctuating decisions on which drugs to include in formularies; allowing the federal government to negotiate drug prices for federal healthcare programs; revising drug rebate calculations under the Medicaid program; and reforming drug importation laws.

Some third-party payors also require pre-approval of coverage for new or innovative devices or therapies before they will reimburse health care providers who use such therapies. While we cannot predict whether any proposed cost-containment measures will be adopted or otherwise implemented in the future, the announcement or adoption of these proposals could have a material adverse effect on our ability to obtain adequate prices for Symvess and our product candidates and operate profitably. Significant cost containment pressure and downward pricing pressures exist in the U.S. and around the world, which may negatively affect reimbursement at any time.

Other Healthcare Laws and Regulations

We are also subject to healthcare regulation and enforcement by the federal government and the states and foreign governments in which we conduct our business. The laws that may affect our ability to operate include but are not limited to:

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the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in exchange for or to induce either the referral of an individual for, or the purchase, order or recommendation of, any good or service for which payment may be made under federal healthcare programs such as the Medicare and Medicaid programs;

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federal false claims laws which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent;

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federal criminal laws that prohibit executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

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the federal Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act (collectively, “HIPAA”), which governs the conduct of certain electronic healthcare transactions and protects the security and privacy of protected health information;

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the federal Physician Payments Sunshine Act, which requires drug and device companies to annually report to CMS all payments and transfers of value provided to physicians and teaching hospitals for posting on a public website; and

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state law equivalents of many of the above federal laws, including anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payor, including commercial insurers.

If our operations are found to be in violation of any of the laws described above or any other governmental laws and regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, the curtailment or restructuring of our operations, the exclusion from participation in federal and state healthcare programs and imprisonment, any of which could adversely affect our ability to operate our business and impact our financial results.

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International Regulation

In addition to regulations in the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial sales and distribution of our future products. Whether or not we obtain FDA approval for a product, we must obtain approval of a product by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country, and the time may be longer or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country.

EU Requirements Applicable to Medicinal Products

In the EU, medicinal products are subject to extensive pre-and post-market regulation by regulatory authorities at both the EU and national levels.

Clinical Trials

Clinical trials of medicinal products in the EU must be conducted in accordance with EU (previously, Directive 2001/20/EC applied; as of January 31, 2022, Regulation EU No 536/2014 applies) and national regulations and the International Conference on Harmonization (“ICH”) guidelines on GCP.

Prior to commencing a clinical trial, the sponsor must obtain a clinical trial authorization from the competent authority, and a positive opinion from an independent ethics committee of the relevant EU Member State in which the clinical trial will be carried out. Any substantial changes to the trial protocol or other information submitted with the clinical trial applications must be notified to or approved by the relevant competent authorities and ethics committees.

The sponsor of a clinical trial must register the clinical trial in advance, and certain information related to the clinical trial will be made public as part of the registration. The results of the clinical trial must be submitted to the competent authorities and, with the exception of non-pediatric Phase 1 trials, will be made public at the latest within 12 months after the end of the trial.

During the development of a medicinal product, the EMA and national medicines regulators within the EU provide the opportunity for dialogue and guidance on the development program. At the EMA level, this is usually done in the form of scientific advice, which is given by the Scientific Advice Working Party of the Committee for Medicinal Products for Human Use (“CHMP”). Advice is not legally binding with regard to any future marketing authorization application of the product concerned. To date, we have not initiated any scientific advice procedures with the EMA, but we have obtained confirmation from the EMA that our ATEVs would be eligible for the EMA’s scientific advice procedures.

Marketing Authorizations

After completion of the required clinical testing, we must obtain a marketing authorization before we may place a medicinal product on the market in the EU. There are various application procedures available, depending on the type of product involved.

All application procedures require an application in the common technical document format, which includes the submission of detailed information about the manufacturing and quality of the product, and non-clinical and clinical trial information. There is an increasing trend in the EU towards greater transparency and, while the manufacturing or quality information is currently generally protected as confidential information, the EMA and national regulatory authorities are now liable to disclose much of the non-clinical and clinical information in marketing authorization dossiers, including the full clinical study reports, proactively or in response to freedom of information requests after the marketing authorization has been granted.

The centralized procedure gives rise to marketing authorizations that are valid throughout the EU. Applicants file marketing authorization applications with the EMA, where they are reviewed by a relevant scientific committee, in most cases the CHMP (although other specialist committees may also be involved; for example, the Committee for Advanced Therapies will also be involved in the review of advanced therapy medicinal products (“ATMP”), and ATEVs could potentially be classified as an ATMP). The EMA forwards CHMP opinions to the European Commission, which uses them as the basis for deciding whether to grant a marketing authorization. The centralized procedure is compulsory for medicinal products that (1) are derived from

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biotechnology processes, (2) contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders, viral diseases or autoimmune diseases and other immune dysfunctions, (3) are orphan medicinal products or (4) are advanced therapy medicinal products. For medicines that do not fall within these categories, an applicant may voluntarily submit an application for a centralized marketing authorization to the EMA, as long as the CHMP agrees that (i) the medicine concerned contains a new active substance, (ii) the medicine is a significant therapeutic, scientific, or technical innovation, or if its authorization under the centralized procedure would be in the interest of public health.

For those medicinal products for which the centralized procedure is not available, the applicant must submit marketing authorization applications to the national medicines regulators through one of three procedures: (1) a national procedure, which results in a marketing authorization in a single EU member state; (2) the decentralized procedure, in which applications are submitted simultaneously in two or more EU member states; and (3) the mutual recognition procedure, in which the EU member states are required to grant an authorization recognizing an existing authorization in another EU member state, unless they identify a serious risk to public health.

Data Exclusivity

Marketing authorization applications for generic medicinal products do not need to include the results of preclinical and clinical trials, but instead can refer to the data included in the marketing authorization of a reference product for which regulatory data exclusivity has expired. If a marketing authorization is granted for a medicinal product containing a new active substance or to a different marketing authorization holder that has carried out a complete set of preclinical tests and clinical trials, that product benefits from eight years of data exclusivity, during which generic marketing authorization applications referring to the data of that product may not be accepted by the regulatory authorities, and a further two years of market exclusivity, during which such generic products may not be placed on the market. The two-year period may be extended to three years if during the first eight years a new therapeutic indication with significant clinical benefit over existing therapies is approved.

There is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product, for example, because of differences in raw materials or manufacturing processes. For such products, while a full set of preclinical tests and trials are not necessary, the results of appropriate preclinical or clinical trials must be provided, and guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product.

Pediatric Development

In the EU, companies developing a new medicinal product must agree to a Pediatric Investigation Plan (“PIP”) with the EMA and must conduct pediatric clinical trials in accordance with that PIP. The marketing authorization application for the product must ordinarily include the results of pediatric clinical trials conducted in accordance with the PIP. It is possible to obtain a deferral, in which case the pediatric clinical trials must be completed at a later date, or a complete waiver from the obligation to conduct pediatric clinical trials (e.g., because the relevant disease or condition occurs only in adults).

Post-Approval Controls

The holder of a marketing authorization is subject to various post-approval controls, such as obligations to maintain a pharmacovigilance system and report adverse reactions, and requirements relating to promotional activities, including a prohibition on the promotion of prescription medicines to the general public. Manufacturers/importers and distributors of medicinal products must obtain authorizations from the competent national authorities and are subject to periodic inspections for compliance with cGMPs and current good distribution practices (“cGDPs”), respectively. The regulatory authorities may also impose specific obligations as a condition of the marketing authorization, such as additional safety monitoring or the conduct of additional clinical trials or post-authorization safety studies.

EU Requirements Applicable to Medical Devices

Under the previous medical devices directive, Directive 93/42/EEC, our ATEVs were not classified as medical devices in the EU because, with limited exceptions, products incorporating or derived from tissues or cells of human origin are expressly

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excluded from the scope of the EU medical devices rules under Directive 93/42. However, as of May 26, 2021, Regulation (EU) 2017/745 applies, and this will bring us within the scope of the EU medical device rules products containing or derived from tissues or cells of human origin that are non-viable or are rendered non-viable.

Medical devices are generally governed by Regulation (EU) 2017/745 on Medical Devices that directly applies in all EU Member States and harmonizes the conditions for placing medical devices on the EU market. This Regulation, however, does not regulate certain important marketing aspects, such as pricing and reimbursement, which remain governed by national law. Additionally, certain areas, such as advertising, may be governed by additional national requirements.

A medical device may be placed on the market within the EU if it conforms to certain “general product safety requirements” or “GSPRs.” These are general in nature and broad in scope. A fundamental GSPR, for example, is that a device must be designed and manufactured in such a way that it will not compromise the clinical condition or safety of patients, or the safety and health of users or other persons.

The manufacturer is obliged to demonstrate that the device conforms to the relevant GSPRs through a conformity assessment procedure. Once the appropriate conformity assessment procedure for a medical device has been completed, the manufacturer must draw up a written declaration of conformity and affix the CE mark to the device. The device can then be marketed throughout the EU.

The nature of the conformity assessment depends upon the classification of the device. The classification rules are mainly based on three criteria: the length of time the device is in contact with the body, the degree of invasiveness, and the extent to which the device affects the anatomy. As a general rule, Class I (low risk) devices are those that do not enter or interact with the body; Class IIa and IIb (medium risk) devices are invasive or implantable or interact with the body; and Class III (high risk) devices are those that affect the vital organs.

Conformity assessment procedures for all but the lowest risk classification of device involve a notified body, which are non-governmental, private entities licensed to provide independent certification of certain classes of medical device. EU regulatory bodies are not involved in the premarket approval of medical devices, with only very limited exceptions (such as medical devices that incorporate a medicinal product as an ancillary substance, in which case these regulatory bodies review the medicinal product). The onus of ensuring a device is safe enough to be placed on the market is ultimately the responsibility of the manufacturer and the notified body.

As part of the conformity assessment procedure, the manufacture will need to conduct a clinical evaluation of the device. This clinical evaluation may consist of an analysis of the scientific literature relating to similar devices, new clinical investigations of the device, or a combination of the two. For Class III and implantable devices, the conduct of clinical investigations is mandatory (with limited exceptions). If a manufacturer wishes to conduct a clinical investigation in the EU, the manufacturer must notify the competent national regulatory authorities in advance and obtain ethics committee approval of the study.

EU Requirements Applicable to Human Cells and Tissues

EU rules, notably Directive 2004/23/EC and other implementing directives, govern the donation, procurement, testing and storage of human cells and tissues intended for human application, whether or not they are medicinal products. These rules also cover the donation, testing, processing, preservation, storage and distribution of human cell and tissues that are not medicinal products. Establishments that conduct such activities must be licensed and are subject to inspection by regulatory authorities. Such establishments must implement appropriate quality systems and maintain appropriate records to ensure that cells and tissues can be traced from the donor to the recipient and vice versa. There are also requirements to report SAEs and reactions linked to the quality and safety of cells and tissues. More detailed rules may exist at the national level.

In addition to regulations in Europe and the United States, we will be subject to a variety of foreign regulations governing clinical trials and commercial distribution of our future products.

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Facilities

Our corporate headquarters, manufacturing, and research and development facilities are located in Durham, North Carolina where we lease approximately 83,000 square feet of space. This space includes approximately 55,000 square feet for production and distribution operations including manufacturing, bioprocessing, quality control, mechanical space and inventory. The remainder of the facility consists of offices, laboratories, and common spaces.

Employees and Human Capital Management

As of December 31, 2025, we had 184 employees, all of whom were full-time. None of our employees are represented by a collective bargaining agreement, and we have never experienced any work stoppages. We believe we have good relations with our employees.

Additional Information

We were incorporated in Delaware on July 1, 2020, under the name Alpha Healthcare Acquisition Corp. in order to effectuate a merger, capital stock exchange, asset acquisition, stock purchase, reorganization or similar business combination with one or more businesses or entities. AHAC completed its initial public offering on September 22, 2020. On August 26, 2021, AHAC and Legacy Humacyte consummated the transactions contemplated by the Merger Agreement. In connection with the closing of the Merger, we changed our name to Humacyte, Inc.

Our principal executive office is located at 2525 East North Carolina Highway 54, Durham, North Carolina 27713, and our telephone number is (919) 313-9633.

Our website address is www.humacyte.com and our investor relations website is located at https://investors.humacyte.com. The information posted on our website is not incorporated into this Annual Report on Form 10-K. The U.S. SEC maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC at http://www.sec.gov. Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act are also available free of charge on our investor relations website as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

We provide notifications of news or announcements regarding our financial performance, including SEC filings, investor events, and press releases, as part of our investor relations website. The contents of these websites are not intended to be incorporated by reference into this report or in any other report or document we file.

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