What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-03-31 compared with 2024-03-28 · 552 added, 538 removed, 894 unchanged (55% of the section changed)

2 unchanged sentences

Humacyte, Inc.

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

is a commercial-stage biotechnology platform company developing universally implantable, bioengineered human tissues at commercial scale, and in the first quarter of 2025 commenced the United States commercial launch of our first FDA-approved product.

We are pioneering the development and manufacture of off-the-shelf, universally implantable, bioengineered human tissues, advanced tissue constructs and organ systems with the goal of improving the lives of patients and transforming the practice of medicine.

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

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

We are initially using our proprietary, scientific technology platform to engineer and manufacture Human Acellular Vessels TM , or HAVs TM .

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

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

The HAV cabinet would initially target the vascular repair, reconstruction and replacement market, including vascular trauma, arteriovenous (“AV”) access for hemodialysis, and peripheral artery disease (“PAD”).

We are also developing the HAV for coronary artery bypass grafting (“CABG”) and pediatric heart surgery.

Over the longer term, we are developing our HAV for the delivery of cellular therapies, including pancreatic islet cell transplantation to treat Type 1 diabetes (our BioVascular Pancreas TM or “BVP”).

We are initially using our proprietary, scientific technology platform to engineer and manufacture acellular tissue engineered vessels, or ATEVs TM .

On December 19, 2024, the FDA granted full approval for the ATEV under the brand name Symvess ™ 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.

Our ATEVs are designed to be easily implanted into any patient without inducing a foreig n body response or leading to immune rejection.

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

The ATEV cabinet is initially targeting the vascular repair, reconstruction and replacement market, including vascular trauma, arteriovenous (“AV”) access for hemodialysis, and peripheral artery disease (“PAD”).

We are also developing the ATEV for coronary artery bypass grafting (“CABG”) and pediatric heart surgery.

Over the longer term, we are developing our ATEV for the delivery of cellular therapies, including pancreatic islet cell transplantation to treat Type 1 diabetes (our BioVascular Pancreas TM or “BVP”).

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

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

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.

2 unchanged sentences

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 higher infection risk that can lead to prolonged hospitalization and limb loss.

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

As of December 31, 2023, our HAVs have been implanted in approximately 573 patients.

We and our collaborators are currently conducting Phase 3 and Phase 2 trials of our 6 millimeter HAV across three therapeutic indications:

vascular trauma, AV access for hemodialysis and PAD.

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

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, 2024, our ATEVs have been implanted in approximately 601 patients.

In addition to vascular trauma, we and our collaborators are currently conducting Phase 3 and Phase 2 trials of our 6 millimeter ATEV in AV access for hemodialysis and 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 HAV for urgent arterial repair following extremity vascular trauma.

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

In September 2023, we announced positive top line results from our V005 Phase 2/3 trial in vascular trauma, and in December 2023 we filed a BLA for urgent arterial repair following extremity vascular trauma when synthetic graft is not indicated, and when autologous vein use is not feasible In February 2024, the FDA accepted the BLA filing and granted Priority Review and set a Prescription Drug User Fee Act (“PDUFA”) date, the FDA action date for its regulatory decision regarding the BLA, of August 10, 2024.

In April 2023, we announced completion of enrollment of our V007 Phase 3 trial of the HAV for use in AV access for hemodialysis.

Upon anticipated completion of our V007 Phase 3 trial in 2024, and dependent upon clinical results, we intend to submit a BLA supplement to the FDA for an indication in AV access for hemodialysis.

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 of products that are intended to diagnose, treat or prevent serious or life-threatening conditions facing American military personnel.

In September 2023, we announced positive topline results from our V005 Phase 2/3 trial in vascular trauma, and in December 2023 we filed a Biologics License Application (“BLA”) for urgent arterial repair following extremity vascular trauma when synthetic graft is not indicated, and autologous vein use is not feasible.

In February 2024, the FDA accepted the BLA filing, granted Priority Review and set a Prescription Drug User Fee

Act (“PDUFA”) date, the FDA action date for its regulatory decision regarding the BLA, of August 10, 2024.

On August 9, 2024, the FDA informed us that it required additional time to complete its review of the BLA for the vascular trauma indication.

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.

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 HAVs of different diameters and lengths at commercial scale.

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.

1 unchanged sentence

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 18 families of patents, many of which generally relate to the scaffolds used to make our vessels, the composition of our vessels and systems and methods of manufacturing our vessels.

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.

3 unchanged sentences

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

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

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.

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

10 unchanged sentences

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

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

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

• 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, isolated from donor tissues and cryopreserved.

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.

2 unchanged sentences

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

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

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

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

The 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:

1 unchanged sentence

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

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

The manufacturing system used to supply our clinical trials from 2016 to 2021, including our Phase 3 trials conducted during that time period, utilized a single tray within one growth drawer holding ten HAVs per batch.

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

Each growth drawer is capable of producing ten 42cm HAVs, each of which is contained within an individual bioreactor bag.

Inside a LUNA200, a tubing network connects all HAVs, allowing the entire system to share nutritive media.

In this way, a single LUNA200 can produce up to 200 HAVs (42cm in length) per batch while maintaining the critical operating parameters, such as biomechanical pulsing, that affect growth.

A thorough comparability assessment was performed to evaluate HAV batches produced in the single drawer system and used in Phase 3 studies versus the 20-drawer LUNA200 system.

The study assessed 22 separate comparisons on the identity, strength, quality, purity, and potency of the HAV product.

In this study, we observed that HAVs produced in the LUNA200 system were comparable to HAVs produced in the single-drawer system.

Additionally, a crossover study, called V011, was conducted in 30 subjects to evaluate HAVs that were manufactured on Humacyte’s commercial LUNA200 platform with the primary goal to evaluate the safety, efficacy and immunogenicity of the LUNA200-manufactured HAVs.

In this trial we have observed comparable safety profile between HAV used in previous studies and the HAV manufactured in the LUNA200 commercial system.

The results of the comparability assessment and the results from the V011 crossover study were submitted to the FDA.

In 2021, the FDA authorized the use of HAVs produced in the commercial LUNA200 system to supply our ongoing clinical trials.

We also plan to use the LUNA200 system to manufacture HAVs for anticipated commercial launch of the HAV if it is approved.

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 LUNA200 TM 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 HAVs in diameter sizes from 3mm to 10mm and lengths from 10cm to 42cm, making the equipment suitable for the varied array of product candidates in our pipeline.

We currently intend to introduce a 13cm-long HAV line extension after the commercial launch of the 42cm HAV for surgeries that require shorter segments of HAV in the setting of vascular trauma and repair.

Using our existing LUNA200 manufacturing equipment without modification, we believe we have the ability to generate 400 HAVs (13cm in length) or 200 HAVs (42cm in length) per manufactured batch.

We have designed our manufacturing system to be functionally closed, to utilize single-use disposable materials with aseptic connections, and to be fully automated, which allows us to control and maximize HAV production.

Based on observations to date, the HAV has withstood maximal pressures that are comparable to those reported for native arteries.

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 HAVs withstanding maximal pressures of approximately 3,200 mmHg before rupturing, making their mechanical properties on par with native human blood vessels.

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 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 HAV in life and limb saving surgeries as demonstrated by their requests to the FDA to use our HAV in multiple expanded access (compassionate use) cases where no alternative was available, as well as requests from Ukrainian surgeons that led to a humanitarian program conducted during the conflict in that country.

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.

Our Initial Market Opportunity in Vascular Repair, Reconstruction and Replacement

10 unchanged sentences

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 HAV 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 HAVs will be a promising alternative that can address critical gaps in existing treatment options for acute vascular injuries due to trauma.

We are developing our HAVs with the goal of providing an effective solution in all time-constrained surgical environments and in resource-limited, infection prone battlefield conditions.

The ability to provide immediately available, non-immunogenic, universally implantable human vessels that are less susceptible to infection represents a clinically significant advantage over existing treatment options.

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, 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 2022, there were over 565,000 patients receiving hemodialysis in the United States.

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.

3 unchanged sentences

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 HAVs, when used as AV access for hemodialysis, can decrease infections and dialysis access failures, which would improve patient outcomes and lower the burden of dialysis costs on the healthcare system.

We expect to file a BLA with the FDA, seeking approval for the use of HAV in AV access for hemodialysis, and to target our commercialization efforts particularly toward those patients who are at high risk of fistula failure or non-maturation, or for those patients at high risk of vascular access infection.

Peripheral Artery Disease (PAD) :

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.

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.

PAD occurs when plaque builds up in arteries that carry blood to the head, organs, and limbs.

PAD usually affects arteries in the legs, but it can also affect arteries that carry blood from the heart to the head, arms, kidneys, and stomach.

We believe our HAVs can be used as a bypass conduit in patients with PAD.

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.

Annual peripheral bypass procedures are over 200,000 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 met with both mixed success and durability compared to conventional surgical bypass.

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.

3 unchanged sentences

Even with the newer insulin delivery technologies, less than one-third of patients achieve consistent target blood sugar levels.

Pancreas transplantation is limited due to the associated morbidity and cost of the whole pancreas organ transplantation procedure.

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 HAVs present a means to deliver a therapeutic number of pancreatic islets to patients with Type 1 diabetes.

Pancreatic islets are embedded on the outer surface of our HAV and implanted as an AV graft, analogous to the outpatient procedure done for hemodialysis access.

After implantation, the islets have the potential to sense blood glucose and then respond by secreting appropriate levels of insulin to maintain proper glucose levels in the blood.

We have termed this new paradigm for pancreatic islet cell delivery the “Biovascular Pancreas (BVP).”

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 “BVP TM .”

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”) :

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 HAVs can replace existing vascular substitutes and improve patient outcomes, particularly in obese patients or those suffering from diabetes, in whom the risks of saphenous vein harvesting are more substantial.

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 200,000 CABG procedures reported annually in the U.S.

4 unchanged sentences

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 HAV product for use in pediatric heart surgery as a Blalock Taussig (“BT”) shunt.

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”.

In 2022, there were 3.7 million babies born in the United States and approximately 1,500 to 2,000 of these babies were born with Tetralogy of Fallot.

The BT shunt is a life-saving procedure for these babies, and we plan to submit an orphan drug application for use of our HAV as a BT shunt for infants born with cyanotic congenital heart defects.

In 2024, there were approximately 1,800 babies born in the United States with Tetralogy of Fallot.

The BT shunt is a life-saving procedure for these babies, and we plan to submit an orphan drug application for use of our 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 Clinical and Pre-Clinical Stage Product Pipeline

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 HAVs 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 one pivotal and one Phase 2 trial in the United States, and currently have seven trials either actively enrolling or in long-term follow-up.

HAVs have been implanted in approximately 85 clinical centers in seven countries around the world, and by more than 100 practicing surgeons.

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

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.

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

Clinical Trial

4 unchanged sentences

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 under review by FDA 30-day PP:

Primary analysis based on a total of 51 patients with injuries of extremities BLA approved by FDA December 19, 2024 30-day PP:

Infection Rate:

Amputation Rate:

V017 Vascular Trauma 2022 Retrospective observational study to evaluate the HAV in real-world setting of humanitarian program conducted during wartime in Ukraine 19 total treated under humanitarian program.

Clinical Trial

Number Indication Begin

Enrollment Design/Phase Number of

Subjects Status Outcomes**

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 30-day PP:

Included in BLA submission approved by FDA December 19, 2024 30-day PP:

Infection Rate:

1 unchanged sentence

Dialysis Access

V001 Dialysis Access 2012 Phase 2 Single-arm 40 10-year follow-up ongoing 30-day PP:

V001 Dialysis Access 2012 Phase 2 Single-arm 40 Completed 30-day PP:

Infection Rate/yr:

Number of Rejections:

V003 Dialysis Access 2013 Phase 2 Single-arm 20 Complete 2-year follow-up 30-day PP:

V003 Dialysis Access 2013 Phase 2 Single-arm 20 Completed 30-day PP:

Infection Rate/yr:

1 unchanged sentence

V006 Dialysis Access 2016 Phase 3 Prospective Randomized Blinded 355 total;

177 received HAV 178 received ePTFE 5-year follow-up in process 30-day PP HAV:

12-month SP HAV:

24-month SP HAV:

177 received ATEV, 178 received ePTFE

Completed 30-day PP ATEV :

12-month SP ATEV :

24-month SP ATEV :

12-month SP ePTFE:

24-month SP ePTFE:

74% Infection Rate HAV/yr:

74% Infection Rate ATEV /yr:

Infection Rate ePTFE/yr:

Number of HAV Rejections:

V007 Dialysis Access 2017 Phase 3 Prospective Randomized Blinded 242 total Enrollment completed April 2023 Trial is currently in 12-month follow up

V011 Dialysis Access 2019 Phase 2 (LUNA200 Manufacturing System Bridging Study) 30 3-year follow-up ongoing 30-day PP:

Infection Rate HAV/yr:

Number of HAV Rejections:

V012 Dialysis Access 2023 Phase 3 Prospective Randomized Blinded Target 150 women total Enrollment ongoing Trial is currently enrolling

Number of ATEV Rejections:

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:

12-month SP ATEV:

6-month SP AVF:

12-month SP AVF:

V011 Dialysis Access 2019 Phase 2 (LUNA200 Manufacturing System Bridging Study) 30 Completed 30-day PP:

Infection Rate ATEV /yr:

Number of ATEV Rejections:

V012 Dialysis Access 2023 Phase 3 Prospective Randomized Blinded Target 150 women total, 76 currently enrolled

Enrollment ongoing Trial is currently enrolling, interim analysis planned on first 80 patients after one-year of follow up

Peripheral Artery Disease

11 unchanged sentences

patent with or without interventions.

As of December 31, 2023, approximately 573 patients worldwide have received our HAVs for the treatment of vascular trauma, AV access for hemodialysis, PAD, and in expanded access cases resulting in approximately 1,203 subject-years of exposure to the HAV.

Our cumulative HAV exposure is approximately 945 subject-years in the hemodialysis access population, 158 subject-years in the PAD population, and 100 subject-years in the arterial trauma population.

The longest our HAV has been in a patient and used for dialysis is more than ten years and there have been more than 113,000 estimated dialysis sessions using our HAVs.

A total of 27 expanded access/compassionate use cases have been granted by the FDA, and another 28 patients with severe PAD have been treated with the HAV under an investigator IND at the Mayo Clinic.

Lastly, 19 patients suffering vascular injuries during the conflict in Ukraine have been treated with the HAV under a humanitarian program.

Throughout all of these trials and other programs, we have observed that our HAVs functioned as intended and provided functional blood flow to affected limbs.

As of December 31, 2024, approximately 601 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 1,277 subject-years of exposure to the ATEV.

Our cumulative ATEV exposure is approximately 993 subject-years in the hemodialysis access population, 168 subject-years in the PAD population, and 115 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 and there have been more than 117,000 estimated dialysis sessions using our ATEVs.

A total of 29 expanded access/compassionate use cases have been granted by the FDA, and another 28 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 HAVs, supporting the potential use of our HAVs as off-the-shelf, universally implantable, bioengineered human tissues.

Overall, the HAV has functioned well and as intended, across ten different clinical trials in three clinical indications.

The HAV has been implanted in approximately 573 patients, across more than 85 clinical sites in seven countries, over more than ten years (as of December 31, 2023).

Rates of primary and secondary patency were similar across trial designs and disease states, with 30-day primary patency ranging from 84% – 100%.

Six-month secondary patency ranges from 84% – 100%, and 12-month secondary patency ranges from 81% – 97%, across multiple clinical trials, disease states, and patient age ranges and demographics.

We have observed zero instances of clinical rejection of the HAV in any clinical trial over the past ten years, suggesting that the HAV was not immunologically rejected after implantation.

Based on clinical trial results to date, we have observed that the HAVs were highly resistant to infection, with an infection rate averaging approximately 1.0% per patient-year in our AV access trials, and low infection rates currently in our trauma and PAD trials.

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.

The ATEV has been implanted in approximately 601 patients, across more than 85 clinical sites in seven countries, over more than ten years as of December 31, 2024.

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.

HAVs 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 HAV became populated with healthy, vascular cells from the patient.

As described in these publications, over time the patient’s cells have been observed to transform the HAV into a multi-layered living tissue similar to native blood vessels.

In these trials we have also observed ongoing cellular repair of HAV tissues that had been previously injured during cannulation with dialysis needles, which suggests that the recellularized HAV may be capable of self-healing.

The image below shows an HAV that had been implanted in a hemodialysis patient for 44 weeks, that had developed alpha-actin positive vascular smooth muscle cells throughout the wall (red staining in the left-hand panel), and had developed a layer of CD31+ endothelial cells on the inner luminal surface of the HAV (line of red endothelial cells indicated in the right-hand panel).

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

HAVs Resistance to 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 HAV was published in the Journal of Vascular Surgery – Vascular Science .

This work compared the infection resistance of the HAV to ePTFE grafts, which are made of plastic.

The laboratory results suggest that the bioengineered human tissue of the HAV may have superior compatibility with the body's own white blood cells as compared to ePTFE.

Histology 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 HAV, which may improve the ability of the HAV to fight dangerous infections once implanted in the body.

Existing Options for Surgical Treatment of Vascular Disease Are Not Sufficient

The table below contains a summary of the efficacy of autologous veins, ePTFE grafts, cryopreserved human cadaveric veins, and preserved bovine veins.

For the treatment of vascular trauma, saphenous vein presents challenges in terms of time to procure the vein, and ePTFE grafts carry extremely high infection rates:

24% – 29% per patient year in the studies below.

Similarly, autogenous fistulas and ePTFE grafts for dialysis access have low functional patencies at six and 12 months, and ePTFE is burdened with high rates of annual infection:

3% – 17% in the studies below.

Both cryopreserved human cadaver vein, and preserved bovine veins, have low patency at 12 months, and also suffer from high rates of aneurysm formation.

Lastly, for bypass of PAD, vein has acceptable patency but is not available for all subjects, while ePTFE carries lower patencies and higher infection risk, and bovine vein becomes aneurysmal at unacceptably high rates.

Published Studies in Vascular Surgery

We derived the data in the table below from data contained in certain published papers on vascular trauma, hemodialysis and PAD between 2002 and the present.

These data are from different studies and thus are not directly comparable.

In addition, many of these papers reported on additional endpoints that are not included in the table below.

Indication Type of

Conduit Year Number of

Patients Published

Outcome Infection

(per patient-year) Rejection

Vascular Trauma Saphenous Vein (autologous) 2002 – 2012 24 12 months:

~78% function 4% N/A

2014 152 30 days:

~90% function N/A

ePTFE (synthetic graft) 2002 – 2012 25 12 months:

~50% function 24% N/A

2005 14 of 95 30 days:

~79% function 29%

Hemodialysis Access Fistula (autogenous) Post-2005 2,800 12 months:

2019 14,892 6 months:

2017 6,439 N/A 4%

2018 602 6 months:

ePTFE (synthetic graft) 2013 128 6 months:

2019 > 400 N/A 3% – 17%

2020 > 3,000 12 months:

Cryovein (cryopreserved human cadaver vein) 2002 45 12 months:

2004 49 12 months:

~65% Aneurysm rate:

Procol (bovine vein) 2005 186 12 months:

66% Aneurysm rate:

3.2% 5.3% N/A

Saphenous Vein (autologous) 2008 60 12 months:

ePTFE (synthetic graft) 2008 61 12 months:

2013 101 12 months:

76% – 89% N/A

2011 273 12 months:

2013 496 N/A 3.8%

Procol (bovine vein) 2008 7 6 months:

50% 12 months:

50% Aneurysm Rate:

Proposed Indication #1:

Use of HAV to Repair Vascular Trauma

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).

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

11 unchanged sentences

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 HAV as a Solution for Vascular Trauma

We believe our HAVs will be a promising alternative that can address critical gaps in existing treatment options for acute vascular injuries due to trauma.

We are developing our HAVs with the goal of providing an effective solution in all time-constrained surgical environments and in resource-limited, infection prone battlefield environments.

The ability to create immediately available, non-immunogenic, universally implantable material that is less susceptible to infection represents a clinically significant advantage over existing options.

Humacyte has a strong working relationship with the Department of Defense (“DoD”) that has led to a partnership over the last decade to support their unmet need to reconstruct and repair vascular injuries through the development of our HAVs.

As a result of this collaboration and partnership with the DoD, we anticipate Humacyte would supply HAVs for use in military hospitals to treat injured soldiers and veterans.

The DoD assigned a priority designation to the HAV technology under Public Law 115-92.

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.

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.

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 continued development of our HAVs for vascular reconstruction and repair.

Regulatory Status of HAV for Vascular Trauma

In May 2023, the FDA granted RMAT designation for use of the HAV 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 when autologous vein use is not feasible.

The BLA submission is 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.

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.

In February 2024, the FDA accepted the BLA filing and granted Priority Review, setting a PDUFA date of August 10, 2024.

V005 Phase 2/3 Trial for Vascular Trauma

On August 9, 2024, the FDA informed us that it required additional time to complete its review of the BLA for the vascular trauma indication.

On December 19, 2024, the FDA granted full approval for Symvess TM (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.

V005 Phase 2/3 Civilian Trial for Vascular Trauma

Trial Design:

Our V005 trial is a single-arm, multi-center, non-randomized clinical trial to evaluate the efficacy, safety and tolerability of our 6 millimeter HAV in replacement or reconstruction of vascular tissues in patients with life or limb-threatening vascular trauma 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 HAV results were systematic literature reviews and meta-analysis of studies evaluating synthetic grafts in vascular injury repair.

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 HAV at 30 days , with 30-day rates of infection and amputation comprising the secondary endpoints.

Status of Phase 2/3 Trial of HAV in Vascular Trauma (as of December 31, 2023)

Number Indication Begin

Enrollment Design/Phase Number of Subjects Status Outcomes**

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 under review by FDA 30-day PP:

Infection Rate:

Amputation Rate:

___________________________

Primary Patency, which is the interval of time of access placement until any intervention designed to maintain or reestablish patency, access thrombosis, or the time of measurement of patency, i.e.

patent without interventions.

Secondary Patency, which is the interval from the time of access placement until abandonment, i.e.

patent with or without interventions.

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:

1 unchanged sentence

Mechanisms of injury included motor vehicle accidents, gunshot wounds, industrial accidents, and falls in the V005 trial.

The HAVs were placed throughout the body, including in the lower limbs and upper limb and were used to repair the axillary artery, femoral artery, popliteal artery and vein, and the brachial artery.

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 HAV 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 HAV has the potential to save valuable time for surgeons in the restoration of blood flow.

As summarized in the table below, the V005 trial met its objectives, and the HAV was observed to have a higher 30-day secondary patency rate, lower amputation rate and lower rate of infection compared to that historically reported for synthetic grafts.

Primary patency for the HAV could not be compared to synthetic grafts as this measure was not reported in the benchmark publications.

V005 results included in the BLA submission to the FDA, and presented in November 2023 VEITHsymposium®, a major vascular surgery conference in New York City, are summarized in the following table.

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

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

HAV Extremity Group (%) Synthetic Graft Benchmark (%)

Primary Patency 84.3% Not reported

ATEV Extremity Group (n=51)

Synthetic Graft Benchmark (%)

Primary Patency 84.3% 78.9%

Secondary Patency 90.2% 78.9%

1 unchanged sentence

Amputations 9.8% 24.3%

The safety profile of the HAV in the V005 trial was consistent with previous studies and there were no cases of clinical rejection of the HAV.

A summary of adverse events for the duration of the study (mean duration of follow up is 295 days) is included in the table below.

V005 Phase 2/3 HAV Adverse Events

Adverse Event V005 Trial - HAV Extremity Group (n=51)

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

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

Primary Patency

Secondary Patency

Conduit Infections

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

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 (%)

2 unchanged sentences

Over Duration of Study

HAV Infections 2 (3.9%)

HAV Rupture 1 (2.0%)

HAV Occlusion/Thrombosis 15 (29.4%)

ATEV Infections

ATEV Occlusion/Thrombosis

Pseudoaneurysm 1 (2.0%)

1 unchanged sentence

Other 2 (3.9%)

There were no unexpected safety signals for the HAV in the V005 trial.

The most common adverse events were thrombosis, anemia, pyrexia, thrombocytopenia, constipation, nausea, peripheral edema, and tachycardia.

The most common non-fatal Serious Adverse Events 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 HAV by an Independent Adjudication Committee.

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 HAV may offer an effective option for revascularization.

A case study from the trial is shown in the figure below, a photograph of an HAV that was used to repair both an artery and a vein in the knee of a patient who suffered a gunshot wound.

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.

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.

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

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:

I n the second quarter of 2022, Humacyte launched a humanitarian initiative to provide its HAVs 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 HAV 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.

I n the second quarter of 2022, Humacyte launched a humanitarian initiative to provide its ATEV s 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 HAV to treat patients with wartime injuries including blast trauma, shrapnel injuries, and gunshot wounds.

The surgeons observed that access to the HAV, 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 were presented at the Military Health System Research Symposium (MHSRS) conference in August 2023.

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.

1 unchanged sentence

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 HAV Results in Vascular Trauma

V017 Ukraine Humanitarian ATEV Results in Vascular Trauma

30-Day Endpoint V017 Trial

HAV Extremity Group (%)

ATEV Extremity Group (%)

Primary Patency 93.8%

2 unchanged sentences

Amputations 0.0%

The safety profile of the HAV in the V017 trial was consistent with previous studies and there were no cases of clinical rejection of the HAV.

A summary of adverse events for the duration of the study (mean duration of follow up is 139 days) is included in the table below.

V017 Ukraine Humanitarian HAV Adverse Events

Adverse Event V017 Trial - HAV Extremity Group (n=16)

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 (%)

2 unchanged sentences

Over Duration of Study

HAV Infections 0 (0.0%)

HAV Rupture* 1 (6.3%)

HAV Occlusion/Thrombosis 1 (6.3%)

ATEV Infections

ATEV Rupture*

ATEV Occlusion/Thrombosis

Pseudoaneurysm 0 (0.0%)

Aneurysm 0 (0.0%)

*One HAV rupture associated with extensive shrapnel remnants that caused bleeding.

*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.

1 unchanged sentence

The patient was initially treated using synthetic graft which became infected, and the patient experienced critical right lower extremity ischemia.

The HAV was implanted as a right superficial femoral artery reconstruction to achieve wound healing and limb salvage.

After three months, the HAV was reported to have retained primary patency with no evidence of HAV infection.

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

Combined V005 and V017 Results of HAV for Vascular Trauma

The BLA submission is supported by the combined results from the V005 Phase 2/3 clinical trial and real-world outcomes from the treatment of wartime injuries in Ukraine in the V017 trial.

Combined results included in the BLA submission to the FDA, and presented in VEITHsymposium, are summarized in the following table.

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

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.

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

30-Day Endpoint V005 Trial

HAV Extremity Group (%) Synthetic Graft Benchmark (%)

Outcome Day 30

Combined ATEV (n=67)

Synthetic Graft Benchmark

Primary Patency

Secondary Patency

Conduit Infections 0.9% 8.4%

Amputations 4.5% 24.3%

The HAV demonstrated a higher 30-day secondary patency rate, and patients treated with the HAV 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 HAV had approximately 1/5 th the amputation rate, and approximately 1/9 th rate of infection compared to that historically reported for synthetic grafts.

Conduit Infection Rate

Amputation Rate

Death Rate (all causes)

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 1/5 th the amputation rate, and approximately 1/9 th 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, 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.

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.

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 HAV for AV Access for Hemodialysis

Use of the ATEV for AV Access for Hemodialysis

Overview of Hemodialysis and Existing Methods of AV Access for Hemodialysis

8 unchanged sentences

Fistulae are often considered the preferred means of access for hemodialysis due to lower infection rates of approximately 0.5% – 1.5% per patient-year as well as long-term durability.

However, many patients are not suitable candidates for fistula placement, due to small vessel anatomy, advanced age, obesity or other comorbidities.

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.

17 unchanged sentences

64.5 % 18.9 % 16.6 %

Published Data in Hemodialysis Access

We derived the data in the table below from data contained in certain published papers on hemodialysis between 2002 and the present.

These data are from different studies and thus are not directly comparable.

In addition, many of these papers reported on additional endpoints that are not included in the table below.

Indication Type of

Conduit Year Number of

Patients Published Secondary

Patency Outcome Infection (per patient-year) Rejection Outcome

Fistula (autogenous) Post‑2005 2,800 12 months:

2019 14,892 6 months:

Hemodialysis Access 2017 6,439 N/A 4%

2018 602 6 months:

ePTFE (synthetic graft) 2013 128 6 months:

2019 > 400 N/A 3% – 17%

2020 > 3,000 12 months:

Cryovein (cryopreserved cadaver vein) 2002 45 12 months:

2004 49 12 months:

~65% Aneurysm rate:

Procol (bovine vein) 2005 186 12 months:

66% Aneurysm rate:

3.2% 5.3% N/A

Overview of HAV Experience in Hemodialysis Access:

A table listing our clinical trials of the HAV in hemodialysis access is included below.

We have implanted the HAV into approximately 392 total patients for hemodialysis access, for a total of more than 945 patient-years of exposure, as of December 31, 2023.

Throughout these trials, we have observed consistent and sustained high primary patency rates, ranging from 95% – 100% at 30 days.

Secondary patency of the HAV at 6 months ranges from 84% – 100%.

Consistently, we have observed zero instances of clinical rejection of any HAV in any hemodialysis access trial.

Implantation of HAV for Hemodialysis

We have also observed in multiple clinical trials that our HAVs had a low infection susceptibility during use for hemodialysis, with a rate lower than 1% per patient-year across all studies.

The low infection susceptibility we observed in our trials of our HAVs may be a result of the HAV’s potential to become a living tissue as it becomes populated by cells from the patient’s body.

Since living tissues are known to have resisted infection due to interactions with host white blood cells and immunological defense systems, it is possible that the repopulated HAV resists infection for the same reasons that native arteries and veins resist infections, as is observed with autogenous fistulas.

We have also observed early evidence of potential healing from the cells that repopulate the HAV after needle puncture for hemodialysis.

In examining HAV explanted segments we have observed healed needle cannulation tracts with cells expressing smooth muscle markers.

This self-healing indicates that the HAV may have repaired itself while being used as a hemodialysis access, which we believe is a distinct feature not present in synthetic materials, and, to our knowledge, has not been observed before for any other regenerative medicine product.

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

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 418 total patients for hemodialysis access, for a total of more than 993 patient-years of exposure, as of December 31, 2024.

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.

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

1 unchanged sentence

Subjects Status Outcomes**

V001 Dialysis Access 2012 Phase 2 Single-arm 40 10‑year follow-up ongoing 30‑day PP:

V001 Dialysis Access 2012 Phase 2 Single-arm 40 Completed 30‑day PP:

Infection Rate/yr:

Number of Rejections:

V003 Dialysis Access 2013 Phase 2 Single-arm 20 Complete 2‑year follow-up 30‑day PP:

V003 Dialysis Access 2013 Phase 2 Single-arm 20 Completed 30‑day PP:

Infection Rate/yr:

1 unchanged sentence

V006 Dialysis Access 2016 Phase 3 Prospective Randomized Blinded 355 total;

177 received HAV 178 received ePTFE 5‑year follow-up in process 30‑day PP HAV:

12‑month SP HAV:

24‑month SP HAV:

177 received ATEV 178 received ePTFE

Completed 30‑day PP ATEV :

12‑month SP ATEV :

24‑month SP ATEV :

12‑month SP ePTFE:

24‑month SP ePTFE:

Infection Rate HAV/yr:

Infection Rate ATEV /yr:

Infection Rate ePTFE/yr:

Number of HAV Rejections:

V007 Dialysis Access 2017 Phase 3 Prospective Randomized Blinded 242 total Enrollment completed in April 2023 Trial is currently in 12-month follow up

V011 Dialysis Access 2019 Phase 2 (LUNA200 Manufacturing System Bridging Study) 30 3‑year follow-up ongoing 30‑day PP:

Infection Rate HAV/yr:

Number of HAV Rejections:

V012 Dialysis Access 2023 Phase 3 Prospective Randomized Blinded Target 150 women total Enrollment ongoing Trial is currently enrolling

Number of ATEV Rejections:

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:

12-month SP ATEV:

6-month SP AVF:

12-month SP AVF:

Clinical Trial

Number Indication Begin Enrollment Design/Phase Number of

Subjects Status Outcomes**

V011 Dialysis Access 2019 Phase 2 (LUNA200 Manufacturing System Bridging Study) 30 Completed 30‑day PP:

Infection Rate ATEV /yr:

Number of ATEV Rejections:

V012 Dialysis Access 2023 Phase 3 Prospective Randomized Blinded Target 150 women total, 76 currently enrolled

Enrollment ongoing Trial is currently enrolling, interim analysis planned on first 80 patients after one-year of follow up

___________________________

7 unchanged sentences

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 HAV for hemodialysis access, with assessments of patency at 6, 12, 18 and 24 months.

In the 60 patients enrolled in these two studies, blood flow through all HAVs was appropriate for hemodialysis, averaging over 1,200 mL/minute.

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.

1 unchanged sentence

Long-term results from the V001 trial showing five-year secondary patency of 58% were published in the European Journal of Vascular and Endovascular Surgery companion journal EJVES Vascular Forum in February 2022, and patients from the V001 trial are currently in a 10-year follow-up period.

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

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 is a prospective, multi-center, multinational, open-label, randomized, two-arm, comparative study.

Eligible study subjects were randomized to receive either a HAV or a commercially available ePTFE graft and followed to 24 months post-implantation by routine study visits.

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.

3 unchanged sentences

The V006 study enrolled 355 subjects who were roughly equally matched in terms of demographics and co-morbidities.

HAV subjects trended older (p=0.06) and had more prior strokes (p=0.02) than did ePTFE subjects.

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

11 unchanged sentences

Prior Stroke (%) 5.6% 12.4% 0.02

The secondary patency of the HAV was greater than that of ePTFE at six and 12 months but lower at 18 and 24 months, an outcome that had not been modelled in the V006 trial design.

As per the pre-specified Cox Proportional Hazards test, the HAV did not achieve its primary efficacy endpoint regarding secondary patency.

In terms of safety, the HAV had a statistically significant lower rate of conduit infections compared to ePTFE.

Substantial differences in antibiotic use and need for hospitalization for infection were also noted in the V006 trial, all favoring the HAV.

The safety advantage of the HAV over ePTFE may be clinically important as infection and sepsis are the second most common cause of death in dialysis patients.

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

HAV HUMANITY [Mean (95% CI)]

ATEV HUMANITY [Mean (95% CI)]

92% (87 – 95%) 82% (75 – 87%) 73% (65 – 79%) 67% (59 – 74%)

2 unchanged sentences

Treatment Group

(HAV vs ePTFE) Hazard Ratio Non-inferiority

(ATEV vs ePTFE)

Hazard Ratio Non-inferiority

Margin Hazard Non-inferiority

4 unchanged sentences

Phase 3 V006 HUMANITY trial rates of infection

The reported Serious Adverse Events (“SAEs”) related to the HAV and ePTFE in the V006 trial, in this patient population, which typically has a high prevalence of existing medical conditions, are detailed in the table below.

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

21 unchanged sentences

Venous stenosis 3(1.7)% 9(5.1)%

Through an Analysis of Panel Reactive Antibodies (“PRA”) in the V006 trial, we observed that subjects that received the ePTFE grafts were more likely to develop antibodies against human tissues, and to become more difficult to crossmatch for a future kidney transplant, than were patients who received the HAV.

While the cause of this improvement in patient responses with the HAV is not clear, this may have been related to the lower number of severe infection events in HAV patients as compared to ePTFE patients in V006.

The percentage of women becoming sensitized (i.e.

cPRA values > 20%) was notably higher in the ePTFE group than the HAV group.

Phase 3 V006 HUMANITY trial % of patients developing antibodies against human tissues

We also observed differences in the remodeling of the HAV and ePTFE implants in the V006 trial.

Consistent with earlier observations from Phase 2 studies, microscopic examination of samples from HAV and ePTFE subjects suggest that the HAVs may have repopulated with host cells and microvasculature, while ePTFE grafts did not repopulate with cells and, in certain cases, fractured at sites of needle cannulation for hemodialysis (“G” is graft;

“D” is defect’ “T” is thrombus (clot);

“L” is lumen;

and “A” is adventitia):

Phase 3 V006 HUMANITY trial microscopic examination of samples from ePTFE and HAV subjects

Comparison of flow rates within the HAV and ePTFE conduits revealed similarities in blood flow and diameter over the 24-month period of the trial.

Bar graphs below display average blood flow rate, maximal blood flow rate, and mid-graft diameters, all of which were measured by periodic ultrasound examinations.

Diameters of the HAV remained close to the nominal 6.0 millimeter diameter.

Average blood flow rates exceeded 1.0 liters/minute, which is generally considered suitable for efficient hemodialysis.

Phase 3 V006 HUMANITY trial blood-flow rates and vessel diameters

Overall, although the primary efficacy endpoint concerning secondary patency was not met, the HAV performed in the V006 trial as was expected, based upon HAV performance in previous Phase 2 trials in hemodialysis and in other clinical applications.

Overall, although the primary efficacy endpoint concerning secondary patency was not met, the ATEV 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 HAV subjects in V006 was somewhat worse than for ePTFE subjects.

In the V006 trial, the HAV displayed significantly fewer infections than did the ePTFE grafts.

This was associated with fewer instances of immune sensitization in HAV subjects as compared to ePTFE subjects, which could translate to easier kidney transplantation at future times.

Similar to prior studies, we observed that the HAV had good durability, blood flow rates and diameters similar to ePTFE grafts, and also host cell remodelling that was superior to that of ePTFE grafts.

In addition, the age and comorbidities of ATEV subjects in V006 was somewhat worse than for ePTFE subjects.

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

2 unchanged sentences

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 HAV for dialysis at six and 12 months as a comparison to autogenous fistulas, which are known to exhibit a high rate of early maturation failure of approximately 40% at six months.

Patients in the study are randomized to receive either the HAV for vascular access or an autogenous AV fistula.

The objective of V007 is to compare the safety and efficacy of our 6 millimeter HAV to autogenous AV fistula for functional hemodialysis access.

Eligible study subjects in V007 are randomized to receive either an HAV or an autogenous fistula and followed to 24 months post-implantation by routine study visits.

After 24 months, patients with functional accesses will be followed for up to five years.

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 HAV and fistula subjects.

Current Trial Status:

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.

We currently expect, upon completion of the V007 trial in 2024 and, dependent upon results, to file a BLA supplement for the use of HAV in AV access for hemodialysis.

Market Phase 3 V012 AV Access Study in Women

Demographics of the patients enrolled in V007 are summarized in the following table.

Phase 3 V007 trial subject demographics

Age, mean (min, max)

57.1 (24, 82)

60.1 (21, 87)

BMI mean value (min, max)

30.2 (19, 49)

History of Diabetes

*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.

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

Co-Primary Endpoints

Functional Patency at Month 6

Secondary Patency at Month 12

Duration of Use Over First 12 Months

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

Subjects (%) n=121

Events Per Patient Year

Subjects (%) n=121

Events Per Patient Year

Treatment Emergent Adverse Events

Serious Adverse Events

Adverse events of special interest:

Study access (SA)-related infections

Clinically significant Steal Syndrome

Rupture of SA

Leading to SA revision or ligation

Leading to SA excision

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

Functional Patency at Month 6

Secondary Patency at Month 12

Duration of Use Over First 12 Months

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 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

Functional Patency at Month 6

Secondary Patency at Month 12

Duration of Use Over First 12 Months

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

Subjects (%) n=54

Events Per Patient Year

Subjects (%) n=56

Events Per Patient Year

Treatment Emergent Adverse Events

Serious Adverse Events

Adverse events of special interest:

Study access (SA)-related infections

Clinically significant Steal Syndrome

Rupture of SA

Leading to SA revision or ligation

Leading to SA excision

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 HAV.

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 the results of this research, we have commenced a clinical study designed to demonstrate the clinical and health economic benefits of the HAV in women dialysis patients, a high-unmet-need population.

Based on the results of the results of this research, we have commenced 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 have commenced a 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 HAV for dialysis in comparison to autogenous fistulas, in female patients currently receiving hemodialysis via catheter.

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 number and severity of infections related to all accesses (including catheters) from access creation until 365 days.

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 76 patients have currently been enrolled in the study.

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 rate of enrollment in the V012 study and on 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:

3 unchanged sentences

Other surgical alternatives include minimally invasive approaches such as stenting and angioplasties that are suitable for smaller atherosclerotic lesions and can delay — but oftentimes not prevent — the ultimate need for surgical revascularization.

Published Data in PAD

We derived the data in the table below from data contained in certain published papers on PAD between 2008 and the present.

These data are from different studies and thus are not directly comparable.

In addition, many of these papers reported on additional endpoints that are not included in the table below.

Indication Type of

Conduit Year Number of

Patients Published Secondary Patency Outcome Infection (per patient-year) Rejection Outcome

Saphenous Vein (autologous) 2008 60 12 months:

– 86% N/A N/A

ePTFE 2008 61 12 months:

(synthetic graft) 2013 101 12 months:

76% – 89% N/A N/A

2011 273 12 months:

2013 496 N/A 3.8%

Procol 2008 7 12 months:

(bovine vein) Aneurysm Rate:

We have observed strong patency rates and no reported cases of infection for the HAV in PAD in clinical studies to date.

We are developing our 6 millimeter HAV for use as a bypass conduit for patients with PAD.

We are conducting two Phase 2 trials to evaluate the safety and efficacy of our 6 millimeter HAV for use as a bypass conduit with PAD, which we refer to as our V002 and V004 trials.

For both of these Phase 2 trials, the HAV is being implanted as a femoral popliteal bypass graft in patients with PAD.

Our Current Phase 2 Trials of the HAV in PAD

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.

Our Current Phase 2 Trials of the ATEV in PAD

Number Indication Begin

20 unchanged sentences

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 HAV as a femoral-to-popliteal bypass graft, and determining the primary, primary assisted, and secondary patency over 12 and 24 months.

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:

1 unchanged sentence

24-month results of the V002 trial were published in 2020.

After censoring for three deaths (none of which were determined to be related to the HAV or the implant procedure), we observed 24-month primary, primary assisted and secondary patency rates of 58%, 58%, and 74%, respectively.

We observed through ultrasound data that the HAVs were mechanically stable during the follow-up period and did not develop aneurysmal dilatation in any patient.

Overall, we also determined through the histological assessment of explanted specimens that there were normal vascular cells within the HAV and there was no infection or signs of immunological reaction to the graft.

There have been no HAV-related infections reported during the V002 trial as of December 31, 2023, and no amputations of the treated extremity.

A sub-set of seven V002 subjects consented for long-term follow-up computerized tomography (“CT”) angiograms, which were obtained at 48 to 52 months after HAV implantation.

In all cases, the HAV maintained normal architecture and function.

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, 2024, 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 HAV with recipient’s vasculature are noted, as is the scale bar on the right-hand side of each image.

The image presents two views of the same subject, and shows uniform HAV diameter along the length of the implant.

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

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.

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.

9 unchanged sentences

Ankle-Brachial Index (median) 0.64 0.90 0.96 — 1.07 0.98 0.94

HAV Infection Rate — 0% 0% 0% 0% 0% 0% 0%

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.

10 unchanged sentences

VascuQol Quality of Life Assessment 3.1 5.6 5.9

In the V004 trial, HAV secondary patency was 86% at 6 months, and 64% at 12 months.

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.

1 unchanged sentence

In addition, ankle-brachial index, a measurement of blood pressure in the operative limb, was increased at 6 and 12 months.

There were no infections of the HAV reported in the V004 trial, despite the severity of the PAD and the often-associated tissue infection that can accompany this disease.

There were zero reports of clinical HAV rejection.

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.

The SAEs reported for the HAV in our V002 and V004 Phase 2 clinical studies in PAD in 35 subjects, a patient population which typically has a high prevalence of existing medical conditions, are summarized in the table below.

SAEs Reported in V002 and V004 Phase 2 Clinical Studies in PAD

Description of SAE Number of SAEs

(% of total subjects)

Number of subjects in V002 and V004 studies

Arterial bypass thrombosis

Anastomotic stenosis

Graft Thrombosis

Vascular Graft Complication

Published literature reports of patients with Rutherford stage 4 and 5 PAD and no autologous vein available for revascularization show that outcomes can include amputation.

1 unchanged sentence

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 HAV in severe PAD.

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

The FDA has granted use of the HAV in 27 special expanded access cases through December 31, 2023.

Each of these compassionate use cases was conducted under an individual, investigator-initiated IND with the FDA.

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 has granted use of the ATEV in 29 special expanded access cases through December 31, 2024, 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.

1 unchanged sentence

The patient is a 70-year-old male with critical limb ischemia and no vein available to perform a bypass, as the vein was previously used for a CABG.

He underwent a successful bypass with the HAV.

He underwent a successful bypass with the ATEV.

Imaging at one year demonstrated a patent graft as illustrated below.

The patient is in long-term follow up.

42-year-old with Infected Dacron Graft

An HAV was used in a 42-year-old female to replace an 8 mm Dacron iliac artery bypass graft that had become infected.

The patient refused harvesting of the femoral vein for reconstruction and requested the HAV.

The patient was seen at one, three, six, nine, and 12 months after HAV implantation.

At all visits, the HAV appeared normal with unobstructed patency.

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.

1 unchanged sentence

At six and 12 months, the graft was functioning well.

At one-year imaging, the HAV was patent and appeared remarkably similar to the patient’s native blood vessels.

The patient had no signs of infection in the HAV and continues to have no limitations or complications during normal activity or exercise.

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, is conducting a study in up to 30 patients with chronic limb-threatening ischemia (CLTI), the end stage of PAD, under an investigator IND filed with the FDA.

In September 2023, researchers presented interim results at the Midwestern Vascular Conference including their conclusion that in the clinical study the HAV was a safe, resilient, and effective conduit for arterial bypass and limb salvage.

The Mayo Clinic, Rochester, MN, is conducting 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 HAV implantation.

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, surgery in 22 (76%) patients necessitated a tibial artery target, a surgical procedure involving the fusion of two 42 cm long HAVs to achieve the required bypass length.

Surgeons reported that the operations to implant the HAV achieved a 100% technical success rate, without any HAV-related major adverse events reported.

At a median follow-up of nine months, the secondary patency rate for patients implanted with the HAV was 72%.

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.

1 unchanged sentence

Pancreatic Islet Transplantation for Type 1 Diabetes (BioVascular Pancreas)

The Biovascular Pancreas (“BVP”) is a modification of Humacyte’s HAV product, leveraging the HAV to deliver therapeutic cells within close proximity of the patient’s bloodstream.

We believe that the HAV extracellular matrix material is both highly biocompatible, as evidenced by adaptive cellular repopulation after implantation, and also highly angiogenic, as evidenced by extensive formation of microvessels surrounding the HAV in vivo.

These attributes mean that the HAV may serve as a suitable conduit for delivering large numbers of therapeutic cells to a patient.

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 HAV has sufficient surface area to accommodate a monolayer of approximately 800,000 human pancreatic islets, which is approximately the number in an entire adult pancreas, and can reverse diabetes and restore glucose control.

We have performed mathematical modelling studies that predict, we believe, that a 42cm HAV could maintain viability of a therapeutic number of islets after implantation of the HAV into the arterial bloodstream, or after implantation as an AV conduit similar to that used for hemodialysis access.

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 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, we commenced testing the BVP in primates.

In these experiments, researchers observed that insulin-producing cells in the BVP survive for multiple weeks after implantation into the animal and continue to make insulin after implantation.

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 (CABG)

Evaluation of 3- and 4mm diameter HAVs for coronary artery bypass is ongoing at Humacyte.

Our initial pilot studies have included the use of our engineered vessels for CABG in canines, demonstrating functional patency and adequate blood flow for up to one month.

To further evaluate the utility and durability of the HAV in a large animal model, we have initiated a preclinical study at Duke University to evaluate the use of our small diameter HAV for CABG in adult primates (baboons).

The goal of this study is to assess patency and function for six to 12 months, as well as host responses and cellular remodeling.

HAVs are followed by ultrasound imaging of the heart, and angiographic imaging of the conduits.

In July 2022, preclinical data on use of the small-diameter HAV in CABG was presented at American Heart Association Basic Cardiovascular Sciences Scientific Sessions.

Coronary bypass in a non-human primate model, with follow-up of six months, showed that the HAV maintained structural integrity and functioned well to conduct blood flow to the heart.

In addition, the HAV was observed to have robust cell repopulation with vascular cells over time, becoming a living vascular tissue supplying the heart muscle.

During 2023 we commenced IND-enabling preclinical studies in large animals to support potential advancement of the HAV into human clinical trials, and these studies are currently ongoing.

Before (left) and after (right) implantation of HAV CABG in baboon

Coronary Artery Bypass Graft

Evaluation of 3.5-4mm diameter ATEVs for CABG has been performed over the last four years at Humacyte.

We performed a preclinical study at Duke University to evaluate the use of our small diameter ATEV for CABG in adult primates (baboons), and we have also performed studies of the sdATEV 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 ATEV, as well as host responses and cellular remodeling.

ATEVs are followed by ultrasound imaging of the heart, and angiographic imaging of the conduits.

In November 2024, researchers presented preclinical results of the sdATEV in a baboon model of CABG at The American Heart Association’s Scientific Sessions 2024 meeting.

In the six-month preclinical CABG model, the sdATEV was observed to sustain patency (blood flow), recellularized with the animals’ host cells, and remodeled to effectively reduce the initial size mismatch between the sdATEV and the animals’ native artery.

In the preclinical study, the sdATEV 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 sdATEV implantation and all sdATEVs 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 sdATEV for CABG.

After implantation, the sdATEV was observed to recellularize with host cells and remodel to effectively reduce the initial size mismatch with the RCA.

Based on discussions with the FDA, we plan to file an IND with the FDA seeking authorization to commence human clinical testing of the sdATEV in CABG.

Angiography showing adaptive remodeling

of ATEV after implant in baboon CABG model

Pediatric Heart Surgery:

1 unchanged sentence

Tetrology of Fallot is a relatively common congenital heart defect, that is often treated using a modified Blalock-Taussig-Thomas (“mBTT”).

To support a potential future IND filing with the FDA, we have evaluated the use of our HAV as an mBTT shunt for up to six months in juvenile primates at the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio.

To support a potential future IND filing with the FDA, we have evaluated the use of our ATEV 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 HAVs into a juvenile large-animal model of pediatric heart disease.

The 3.5mm HAV 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 HAV’s patency, structure, and blood flow from one week to six months after the implant.

The 3.5mm diameter HAV has smaller product dimensions but is manufactured using a similar process as Humacyte's 6mm HAV system currently being evaluated in clinical trials in vascular trauma, AV access for hemodialysis, and PAD.

We believe that the production of the functional 3.5mm HAV is indicative of the potentially broad application of our proprietary bioengineered tissue platform and manufacturing processes.

Imaging of 3.5mm HAV mBTT shunt in juvenile primate followed for 6 months

In the study, researchers implanted 3.5mm diameter ATEVs into a juvenile large-animal model of pediatric heart disease.

The 3.5mm ATEV 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 ATEV’s patency, structure, and blood flow from one week to six months after the implant.

The 3.5mm diameter ATEV has smaller product dimensions but is manufactured using a similar process as Humacyte's 6mm ATEV 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 ATEV is indicative of the potentially broad application of our proprietary bioengineered tissue platform and manufacturing processes.

Engineered Trachea for Treatment of Severe Airway Injuries

3 unchanged sentences

The lack of a functional tracheal conduit commits patients to, sometimes, slow suffocation.

We have modified the HAV production process to enable the embedding of a biocompatible medical-grade stent within the wall of the engineered vessel.

Combining a non-degradable stent with the degradable polymer scaffold used for HAV production results in a composite scaffold that can be seeded with smooth muscle cells and grown in culture.

After decellularization, the engineered trachea consists of the extracellular matrix contained in the HAV, along with an embedded stent that prevents the collapse of the engineered airway with inspiration or neck movements.

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

13 unchanged sentences

Recognizing that commercial scale production capacity of bioengineered tissue has been non-existent, we prioritized the development of a scalable, reproduceable, commercial biomanufacturing process.

At our 83,000 square foot manufacturing facility in Durham, North Carolina, we have industrialized this concept and created a scalable modular manufacturing process that enables us to engineer our HAVs in commercial quantities in a system designed for cGMP compliance.

The system used to produce HAVs for use in our clinical trials from 2016 to 2021, including Phase 3 trials, utilized a single tray within one growth drawer holding ten HAVs per batch.

These batches were manufactured at a contract manufacturer.

The current, commercial-scale LUNA200 system utilizes 20 growth drawers holding ten HAVs each for a total of 200 HAVs per batch.

Since 2021 this system has been utilized to produce clinical product for use in our ongoing Phase 3 trials, and is planned for use to supply our anticipated commercial launches upon approval.

Our manufacturing process utilizes our LUNA200 system, consisting of 20 “growth drawers.” Each growth drawer is capable of producing ten 42cm HAVs and each HAV remains contained within an individual bioreactor bag.

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.

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.

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 HAVs per batch while maintaining the critical operating parameters that direct growth, creating a gross capacity of approximately 900 HAVs per system annually.

A thorough comparability assessment was performed to evaluate HAV batches produced in the single-drawer system versus batches produced in the 20-drawer LUNA200 system.

The study assessed 22 separate comparisons on the identity, strength, quality, purity, and potency of the HAV product.

In this study, we observed that HAVs produced in the LUNA200 system were comparable to HAVs produced in the single-drawer system.

Additionally, a crossover study, called V011, enrolled 30 subjects to evaluate HAVs that were manufactured on Humacyte’s commercial LUNA200 platform with the primary goal to evaluate the safety, efficacy and immunogenicity of the LUNA200-manufactured HAVs.

In this trial we observed comparable safety profile between HAV used in previous studies and the HAV manufactured in the LUNA200 commercial system.

The results of the comparability assessment and from the V011 crossover study were submitted to the FDA.

In 2021, the FDA authorized the use of HAVs produced in the commercial LUNA200 system to supply our ongoing clinical trials.

We plan to also use the LUNA200 system for anticipated commercial launches of the HAV if it is approved.

We have designed the LUNA200 to have the ability to produce HAVs in diameter sizes from 3mm to 10mm and lengths from 10cm to 42cm, making the equipment suitable for the varied array of product candidates in our pipeline.

We intend to introduce a 13cm HAV line extension after commercial launch of the 42cm HAV.

Using our existing LUNA manufacturing equipment, we can generate 400 13cm HAVs per batch.

Our modular manufacturing platform can be scaled without impacting the operating parameters that support the HAV growth process.

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 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.

Modular Manufacturing Platform Allows for Production of Multiple Product Lengths Using the Same Equipment

We currently have eight LUNA200 systems installed, commissioned and qualified in our manufacturing facility, creating an annual gross HAV capacity of approximately 7,200 HAVs.

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.

1 unchanged sentence

The initiation and pace of the expansion of vessel capacity will be determined based on our assessment of market opportunity.

We initiate HAV production using primary human aortic vascular cells from a working cell stock (“WCS”) that is isolated from FDA-compliant donor tissues and cryopreserved.

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 HAV manufacturing utilizing biochemical and gene expression assays.

Each qualified primary isolation can produce approximately 500,000 to one million HAVs.

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.

3 unchanged sentences

After completion of the culture period, we decellularize the bioengineered vessel using a proprietary combination of salts, enzymes and detergents, followed by numerous washes in excipient grade neutral pH buffered saline.

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

After decellularization, our HAVs are packaged for distribution inside the same flexible bioreactor bag in which they were produced, with sterile phosphate buffered saline as the excipient.

Once the package is delivered to the operating room, the HAV is removed from the bioreactor bag by the surgical staff.

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.

We source critical components and necessary raw materials from vendors that have been approved and qualified through our vendor management program.

6 unchanged sentences

Supply Agreement with SeraCare

In January 2014, we entered into a supply agreement with SeraCare for the supply of human plasma, which was amended in October 2018.

We refer to the supply agreement, as amended, as the SeraCare Agreement.

In January 2014, we entered into a supply agreement with SeraCare for the supply of human plasma, which was amended in October 2018 (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.

1 unchanged sentence

The SeraCare Agreement is subject to annual price modifications in the case of significant changes in SeraCare’s cost of raw materials, with any modification to be determined at least three months prior to the end of the relevant year.

The initial term of the SeraCare Agreement expires on October 12, 2023, but automatically extends for subsequent one-year periods unless terminated by either party at least 18 months prior to the end of the initial term.

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.

3 unchanged sentences

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.

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.

8 unchanged sentences

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

For our vascular repair and replacement applications of our technology, including renal replacement therapy for dialysis access, the treatment of PAD, and the treatment of vascular trauma, we have retained the right to commercialize our HAV within the United States, and expect to commercialize the HAV through a combination of our own direct sales and marketing team combined with our partnership with Fresenius Medical Care, described below.

We plan to own end-to-end commercialization while pursuing collaborations with appropriate strategic partners who have established distribution channels for supplying customer care centers.

Our first expected market launch, in the treatment of vascular trauma, is a highly concentrated market of approximately 200 Level I Trauma Centers that may be reached with a small field sales forces of no more than 20 representatives.

Many of the major trauma centers already have familiarity with our HAV product candidate through their participation in our clinical trials.

Our sales effort will include dual targeting of surgeons to create pull-through demand and hospital administration (trauma center Value Analysis Committees) to assure adoption and uptake of the HAV in vascular trauma.

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.

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 recruited and trained a highly experienced sales team for the commercial launch of Symvess.

All ten sales team members are multi-year President’s Club winners, representing the top 10% of achievers in their prior sales organizations.

The average hospital medical device and biotech experience of our sales team members exceeds 15 years, all sales team members have experience in vascular surgery and/or trauma surgery, and 80% have previous experience selling regenerative therapies.

All team members have experience selling clinically differentiated disruptive technologies and premium priced portfolios.

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.

Additionally, we submitted a New Technology Add-On Payment (“NTAP”) application for Symvess to the Centers for Medicare and Medicaid Services (“CMS”) in October 2024.

We presented Symvess data at a public Town Hall with the CMS in December 2024.

If successful, NTAP reimbursement will begin for discharges on October 1, 2025, offering hospitals additional payment to cover a portion of the costs associated with Symvess.

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 HAV and all improvements thereto, and modifications and derivatives thereof (including any changes to the length, diameter or configuration of the foregoing), for use in vascular creation, repair, replacement or construction, including renal replacement therapy for dialysis access, the treatment of 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.

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.

13 unchanged sentences

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.

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.

4 unchanged sentences

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.

We anticipate that coverage and reimbursement by the CMS and private payors will be essential for most patients and health care providers to afford our treatments, particularly in the applications of renal replacement therapy for dialysis access and the treatment of PAD.

Accordingly, sales of our products will depend substantially, both domestically and abroad, on reimbursement by government authorities, private health coverage insurers and other third-party payors.

Our strategy around HAV reimbursement focuses on achieving alignment and agreement from CMS on coding and payment pathways;

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 HAV product opportunities.

We are pursuing a dual regulatory and legislative reimbursement strategy to ensure separate Medicare payment for the HAV at an appropriate price.

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.

1 unchanged sentence

See “Risk Factors — Risks Related to the Development and Commercialization of Our Product Candidates” for further information.

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

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.

11 unchanged sentences

Our 15 families of patents are comprised of:

(i) nine 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, ten pending U.S.

non-provisional patent applications, one pending PCT patent application and eight pending foreign applications in Australia, Canada, China, Europe, Japan and Hong Kong, which are solely owned by us,

(i) Twelve issued U.S.

patents, 73 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, seven pending U.S.

non-provisional patent applications, and 12 pending foreign applications in Australia, Canada, China, Europe, Japan and Hong Kong, which are solely owned by us,

(ii) three issued U.S.

patents, 18 issued foreign patents in Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Japan, Netherlands, Spain, Sweden, Switzerland, Turkey, and the UK, one pending U.S.

non-provisional patent application, and three pending foreign patent applications in Europe and Canada, which we co-own, and

non-provisional patent application, and four pending foreign patent applications in Europe and Canada, which we co-own, and

(iii) one issued U.S.

patents, two issued or granted foreign patents in Europe and Japan, one pending U.S.

non-provisional patent application, and six pending foreign patent applications in Australia, Canada, Europe, Japan, China, and Hong Kong, which we exclusively license.

Many of these patents and patent applications generally relate to the scaffolds used to make our vessels, the composition of our vessels, and systems and methods of manufacturing our vessels.

patent, one issued foreign patent in Japan, one pending U.S.

non-provisional patent application, and five pending foreign patent applications in Australia, Canada, Europe, Japan, 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 our vessels expires in 2032, 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 our vessels expires in 2032.

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.

If granted, we estimate that the expiration of the patent will be extended by approximately 50 months.

patent relating to the entangler machinery used to make tubular scaffolds expires in 2035.

Included in our patent portfolio are 12 pending, Humacyte-owned non-provisional applications relating to the manufacturing of engineered tissues at commercial scale, as well as other technologies and product candidates.

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.

16 unchanged sentences

License Agreement with Duke University

In March 2006, we entered into a license agreement with Duke University (“Duke”), which was subsequently amended in 2011, 2014, 2015, 2018, 2019 and January 2022.

We refer to the license agreement, as amended, as the Duke License Agreement.

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.

17 unchanged sentences

License Agreements with Yale University

Large Diameter HAV

In August 2019, we entered into a license agreement with Yale University (“Yale”) that granted us a worldwide license to the patents jointly owned with us related to tubular prostheses which are large diameter versions of our vessels, which may or may not contain a stent.

The license granted under the agreement is exclusive in the field of engineered urinary conduits, engineered tracheae/airways and engineered esophagi, except that it is subject to Yale’s non-exclusive right, on behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes.

Large Diameter ATEV

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.

1 unchanged sentence

We may also sublicense our rights without Yale’s prior written consent, but such sublicense is subject to certain conditions.

In connection with our entry into the Yale License Agreement, we paid Yale an upfront cash fee of less than $0.1 million.

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:

4 unchanged sentences

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

The agreement expires on a country-by-country basis on the date on which the last of the patents in such country expires, lapses or is declared invalid.

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.

2 unchanged sentences

10,172,707 will expire no earlier than 2035.

Yale may terminate the agreement if we fail to (i) provide written diligence reports, (ii) provide a commercially reasonable diligence plan, (iii) implement the plan in accordance with the obligations under the agreement, or (iv) reach certain research and development milestones within the scheduled timeframe set forth in the agreement;

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 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.

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.

1 unchanged sentence

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 license granted under the agreement is exclusive in the field of acellular vascular tissues that deliver pancreatic islet cells to patients, except that it is subject to Yale’s non-exclusive right, on behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes.

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.

1 unchanged sentence

We may also sublicense our rights without Yale’s prior written consent, but such sublicense is subject to certain conditions.

In connection with our entry into the Yale License Agreement, we paid Yale an upfront cash fee of less than $0.1 million.

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:

4 unchanged sentences

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

The agreement expires on a country-by-country basis on the date on which the last of the patents in such country expires, lapses or is declared invalid.

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.

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.

We may terminate the license agreement (i) on 90 days’ prior written notice to Yale, provided we are not in breach of the license agreement and have made all required payments to Yale thereunder and on written notice to Yale following an uncured material breach.

Our rights under the license agreement will also terminate automatically with respect to a patent application or patent within the licensed patents in a specified country if, upon receipt of written notice from Yale, we do not agree to pay the patent filing, prosecution and maintenance fees incurred by Yale for such patent applications or patents in the specified country.

We 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.

13 unchanged sentences

Furthermore, time is required to prepare the vein harvest site and to remove the vein from the leg, which adds to ischemia time and can increase the risk of tissue and limb loss.

Rates of traumatic limb loss are strongly tied to ischemia time, and therefore rapid revascularization using an off-the-shelf HAV conduit may decrease ischemia time and lead to better outcomes.

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.

24 unchanged sentences

Some of these products require rinsing to remove toxic chemicals used for storage.

We believe our HAVs combine the off-the-shelf availability of synthetic grafts with the regenerative capabilities of autologous vessels.

We believe 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 states, including atherosclerosis, end-stage kidney disease, coronary artery disease, vascular trauma, pediatric congenital heart disease, airway disease, and others.

We believe that the HAV’s multiple key characteristics will drive rapid clinical adoption amongst surgeons and the broader healthcare community:

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 HAVs of varying diameters and lengths is designed to be stored on-site at facilities such as hospitals, trauma centers and outpatient surgical centers.

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 HAVs are available for immediate use by opening and removing the HAV from its original flexible bioreactor bag.

Since our HAV does not need flushing, harvesting or thawing, as is common with other vascular substitute alternatives, we believe hospitals will be able to use our HAVs for vascular surgery more quickly with smaller surgical teams, reduced logistics and decreased overall cost.

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 HAVs does not subject patients to the serious operation of harvesting an autologous vein, which can result in greater procedure and recovery time, potential scarring and disfigurement, increased costs, and numerous potential health complications.

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 HAVs have the potential to be universally implantable and durable across patients.

Because our HAVs are derived from human tissue (but cleansed of all cells and cellular components), we believe (and have observed in clinical trials to date) that they do not generate the foreign body response associated with the use of synthetic grafts, or the immune response associated with cryopreserved vessels.

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 HAVs as compared to synthetic materials.

As a result, we believe our HAVs may be used in complicated and potentially contaminated wounds with fewer patient complications following the initial procedure.

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 HAVs to precise specifications under controlled quality standards, which will allow surgeons the flexibility to quickly and easily select an HAV in the appropriate size and shape for each indication.

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 HAVs repopulate with the patient’s own vascular cells, creating a living vascular tissue with the associated long-term benefits of self-healing and infection resistance.

If approved, we expect our HAVs would compete with the use of a patient’s own blood vessels, as well as a variety of marketed products, such as conventional synthetic grafts, xenografts, and allografts, as well as developing technologies.

We expect the key competitive factors affecting the commercial success of our HAVs to likely be efficacy, safety, convenience, pricing and reimbursement.

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

3 unchanged sentences

Xenografts, such as Artegraft ® and Procol ® , are processed animal-derived vessels, while allografts are processed allogeneic cellular vessels, such as CryoVein ® and AngioGRAFT ® .

There are also a number of companies of which we are aware that have preclinical and early clinical-stage research programs underway to develop products that could potentially compete with our HAVs, including NovaHep AB, Xeltis AG, Hancock Jaffe, and Vascudyne Inc.

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.

2 unchanged sentences

Government Regulation

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

In the United States, the FDA regulates pharmaceutical drugs, medical devices and biologic products under the Federal Food, Drug, and Cosmetic Act (“FDCA”), the Public Health Service Act (“PHSA”), FDA implementing regulations, and other laws.

Our vessels are subject to regulation by the FDA as biologics.

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.

None of our vessels have been approved by the FDA for marketing in the United States, and we currently have one BLA pending.

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.

6 unchanged sentences

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

• Submission to the FDA of an Investigational New Drug application (“IND”), which must become effective before human clinical trials in the United States may begin;

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

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

4 unchanged sentences

to assure that the facilities, production methods, testing and controls are adequate;

and, if applicable, to assure compliance with cGTP requirements for human cellular and tissue-derived products;

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

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

3 unchanged sentences

Biological Products Development Process

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

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.

15 unchanged sentences

Information about clinical trials must be submitted within specific timeframes to the National Institutes of Health (“NIH”) for public dissemination on its ClinicalTrials.gov website.

For purposes of BLA submission and approval, clinical trials are typically conducted in three sequential phases, which may overlap or be combined.

For 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.

5 unchanged sentences

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.

31 unchanged sentences

The FDA may not grant approval on a timely basis, or at all.

Even if we believe a clinical trial has demonstrated safety and efficacy of one of our vessels for the treatment of a disease, the results may not be satisfactory to the FDA.

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 our vessels.

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.

6 unchanged sentences

This bar does not apply to submission or approval of full BLAs.

Because FDA has determined that our HAVs are regulated as biologics and require a BLA for marketing, we believe that our lead product will be entitled to 12 years of exclusivity upon approval.

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.

30 unchanged sentences

Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a biological product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a biological product available in the United States for this type of disease or condition will be recovered from sales of the product.

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.

27 unchanged sentences

Post-Approval Requirements

Any biologics manufactured or distributed by us or our collaborators pursuant to FDA approvals would be subject to continuing post-approval regulation by the FDA, including recordkeeping requirements and reporting of adverse experiences associated with the product, as well as any post-marketing surveillance requested by the FDA as a condition to BLA approval.

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.

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.

13 unchanged sentences

Third-Party Payor Coverage and Reimbursement

Although none of our vessels have been commercialized for any indication, if they are approved for marketing, commercial success of our vessels will depend, in part, upon the availability of coverage and reimbursement from third-party payors at the federal, state and private levels.

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.

8 unchanged sentences

Some third-party payors also require pre-approval of coverage for new or innovative devices or therapies before they will reimburse health care providers who use such therapies.

While we cannot predict whether any proposed cost-containment measures will be adopted or otherwise implemented in the future, the announcement or adoption of these proposals could have a material adverse effect on our ability to obtain adequate prices for our vessels and operate profitably.

Significant cost containment pressure and downward pricing pressures exist in the U.S.

27 unchanged sentences

Advice is not legally binding with regard to any future marketing authorization application of the product concerned.

To date, we have not initiated any scientific advice procedures with the EMA, but we have obtained confirmation from the EMA that our HAVs would be eligible for the EMA’s scientific advice procedures.

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

5 unchanged sentences

Applicants file marketing authorization applications with the EMA, where they are reviewed by a relevant scientific committee, in most cases the CHMP (although other specialist committees may also be involved;

for example, the Committee for Advanced Therapies will also be involved in the review of advanced therapy medicinal products (“ATMP”), and HAVs could potentially be classified as an ATMP).

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.

7 unchanged sentences

Marketing authorization applications for generic medicinal products do not need to include the results of preclinical and clinical trials, but instead can refer to the data included in the marketing authorization of a reference product for which regulatory data exclusivity has expired.

If a marketing authorization is granted for a medicinal product containing a new active substance or to a different marketing authorization holder that has carried out a complete set of pre-clinical tests and clinical trials, that product benefits from eight years of data exclusivity, during which generic marketing authorization applications referring to the data of that product may not be accepted by the regulatory authorities, and a further two years of market exclusivity, during which such generic products may not be placed on the market.

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 pre-clinical tests and trials are not necessary, the results of appropriate preclinical or clinical trials must be provided, and guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product.

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

7 unchanged sentences

EU Requirements Applicable to Medical Devices

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

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 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.

49 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business