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Item 1. Business

2024-03-28 compared with 2023-03-24 · 231 added, 174 removed, 1201 unchanged (25% of the section changed)

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

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

arteriovenous (“AV”) access for hemodialysis;

peripheral artery disease (“PAD”);

and coronary artery bypass grafting (“CABG”).

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

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

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

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.

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

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

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

In addition, in many instances of vascular trauma, the patient may not have adequate vein available to make autologous graft repair feasible.

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.

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

We are currently conducting Phase 2 and Phase 3 trials of our 6 millimeter HAV across two therapeutic indications, vascular trauma and AV access for hemodialysis, as well as continuing long-term follow up of patients in our Phase 2 PAD studies.

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.

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.

Upon completion of our Phase 3 trials, we intend to submit a Biologics License Application (“BLA”) to the FDA for an indication in vascular trauma and AV access for hemodialysis.

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.

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

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

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

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

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

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

Our Proprietary Scientific Technology Platform

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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, utilized a single tray within one growth drawer holding ten HAVs per batch.

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.

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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 are manufactured on Humacyte’s commercial LUNA200 platform with the primary goal to evaluate the safety, efficacy and immunogenicity of the LUNA200-manufactured HAVs.

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.

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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 for anticipated commercial launches of the HAV if it is approved.

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

Our current 83,000 square foot manufacturing facility has space to further expand manufacturing capacity as needed to over 40 LUNA200 systems.

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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 commercial launch of the 42cm HAV for surgeries that require shorter segments of HAV in the setting of vascular trauma and repair.

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.

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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.

Our Initial Market Opportunity in Vascular Repair, Reconstruction and Replacement

We believe there is a significant market opportunity for our technology across a number of important clinical areas within vascular reconstruction and replacement including vascular trauma, AV access for hemodialysis, peripheral artery disease, and adult cardiac surgery.

To treat these diseases and conditions, patients often require invasive cardiovascular surgery, which involves the use of alternative vascular synthetic materials or autologous vessels harvested from elsewhere in the body.

To treat these diseases and conditions, patients often require invasive vascular and cardiovascular surgery, which involves the use of alternative vascular synthetic materials or autologous vessels harvested from elsewhere in the body.

For more information about our evaluation of market opportunity, see “Risk Factors — Risks Related to the Development and Commercialization of Our Product Candidates — The sizes of the market opportunities for our product candidates have not been established with precision and are estimates that management believes to be reasonable.

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Furthermore, these injuries account for greater than 20% of all trauma-related deaths.

Civilian patients with central or peripheral vascular injuries are estimated to account for approximately 80,000 of all injuries reported in trauma patients in the United States, inclusive of urgent and iatrogenic vascular trauma injuries.

However, these injuries 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 environments.

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.

Arteriovenous Access for Hemodialysis :

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.

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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.

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.

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

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

We have termed this new paradigm for pancreatic islet cell delivery the “Biovascular Pancreas (BVP).” Proof-of-concept studies in rodents and pigs have shown promise that the BVP can reduce glucose levels.

Studies in non-human primates are planned to commence in 2023.

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 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.

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Pediatric Heart Surgery :

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

The BT shunt is a surgical procedure that is used to increase pulmonary blood flow for the treatment of babies born with a complex congenital heart defect called Tetralogy of Fallot, a common type of “blue baby syndrome”.

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Our Clinical and Pre-Clinical Stage Product Pipeline

The following table highlights key information about our current 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 Phase 2 trial in the United States, and currently have seven trials either actively enrolling or in long-term follow-up.

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.

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Vascular Trauma

V005 Vascular Trauma 2018 Phase 2/3 Single-arm Historical Comparator Unblinded A total of 60 patients enrolled as of December 31, 2022.

Primary analysis will be based on a total of 50 patients with injuries of extremities, 42 of which have been enrolled as of December 31, 2022 Enrolling Trial is currently enrolling

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:

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.

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:

Infection Rate:

Amputation Rate:

Dialysis Access

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

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

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

12-month SP HAV:

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Number of HAV Rejections:

V007 Dialysis Access 2017 Phase 3 Prospective Randomized Blinded Target 240 total;

230 enrolled (as of December 31, 2022) Enrolling Trial is currently enrolling

V011 Dialysis Access 2019 Phase 2 (LUNA200 manufacturing system) 30 3-year follow-up ongoing 30-day PP:

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

Peripheral Artery Disease

V002 Peripheral Artery Disease 2013 Phase 2 Single-arm 20 10-year follow-up ongoing 30-day PP:

2013 Phase 2 Single-arm 20 10-year follow-up ongoing 30-day PP:

Infection Rate/yr:

Number of Rejections:

V004 Peripheral Artery Disease 2016 Phase 2 Single-arm 15 5-year follow-up ongoing 30-day PP:

2016 Phase 2 Single-arm 15 Completed 30-day PP:

Infection Rate/yr:

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patent with or without interventions.

As of December 31, 2022, approximately 533 patients worldwide have received our HAVs for the treatment of trauma, AV access for hemodialysis, PAD, and in expanded access cases resulting in approximately 1,080 subject-years of exposure to the HAV.

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 nine years and there have been more than 106,000 estimated dialysis sessions using our HAVs.

Additionally, a total of 26 expanded access/compassionate use cases have been granted by the FDA, and another 18 patients with severe PAD have been treated with the HAV under an investigator IND at the Mayo Clinic.

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

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.

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Furthermore, we have observed no evidence of clinically relevant immunologic reactions to our HAVs, supporting the potential use of our HAVs as off-the-shelf, universally implantable, bioengineered human tissues.

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

The HAV has been implanted in approximately 533 patients, across approximately 85 clinical sites in seven countries, over more than nine years (as of December 31, 2022).

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 nine years, suggesting that the HAV was not immunologically rejected after implantation.

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.

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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

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3.2% 5.3% N/A

Peripheral Artery Disease Saphenous Vein (autologous) 2008 60 12 months:

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:

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Synthetic materials have been shown to be inferior to autologous vein in resistance to infection and durability and, therefore, are generally only used for vascular repair when autologous vein is not an option.

Our Solution for Vascular Trauma

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.

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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.

Our Current Phase 2/3 Trial for Vascular Trauma

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.

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

Trial Design:

Our ongoing V005 trial is a single-arm, multi-center, non-randomized clinical trial to evaluate the efficacy, safety and tolerability of our 6 millimeter HAV in replacement or reconstruction of vascular tissues in patients with life or limb-threatening vascular trauma.

Since the V005 trial is a single-arm, non-randomized, open label study, we have the ability to track ongoing efficacy and safety.

The primary efficacy endpoint will evaluate patency of the HAV at 30 days based on an assessment of 50 patients from the V005 trial who have vascular trauma of the extremity, excluding torso injuries and iatrogenic trauma patients.

The Company plans to file a BLA with the FDA for an indication in vascular trauma approximately four months after completion of the V005 trial.

The Company plans to seek accelerated approval of the HAV for urgent arterial repair following extremity vascular trauma when synthetic graft is contraindicated and when autologous vein is not feasible.

Results from patients from V005 outside of the primary endpoint population, as well as results from patients treated in the Ukraine humanitarian program, will be included in the BLA as supportive data.

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.

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)

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Enrollment Design/Phase Number of Subjects Status Outcomes**

V005 Vascular Trauma 2018 Phase 2/3 Single-arm Historical Comparator Unblinded A total of 60 patients enrolled as of December 31, 2022.

Primary analysis will be based on a total of 50 patients with injuries of extremities, 42 of which have been enrolled as of December 31, 2022 Enrolling Trial is currently enrolling

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:

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patent with or without interventions.

Current Trial Status:

As of December 31, 2022, we had 17 clinical trial sites for the V005 trial in the United States and four in Israel.

We are in the process of adding to the trial sites in Ukraine which are currently participating in the ongoing humanitarian program.

The range of trauma injuries in V005 has been broad, including penetrating trauma cases, blunt injury cases, and iatrogenic injuries.

Mechanisms of injury have included motor vehicle accidents, gunshot wounds, industrial accidents, falls, and iatrogenic injuries from other interventional or surgical procedures.

The HAVs have been placed throughout the body, including in the lower limbs, upper limb, and torso.

The HAV has been used to repair the axillary artery, femoral artery, popliteal artery and vein, and the brachial artery in the V005 trial.

Many of the injuries treated in the V005 trial, including industrial accidents, motor vehicle accidents, and some gunshot wounds, are contaminated injuries that are at elevated risk of graft infection.

Nonetheless, as of December 31, 2022, there has been only one report of HAV infection in any V005 subject, despite a number of instances where the HAV has been implanted into contaminated surgical fields of acute vascular wounds.

There have been several instances of local wound infections, but importantly only one of these instances has led to infection of the HAV material itself, which we believe represents a significant advantage of the HAV over ePTFE grafts, which have a higher propensity to become infected in contaminated or infected wound beds.

There have been no reports of limb amputation that occurred as a result of HAV malfunction or loss of patency.

The resistance to

infection we have observed in trials to date is particularly important in traumatic injuries which are often caused by infected material (i.e., knife, car accident, blast injury).

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

V005 Trial Results:

For the primary analysis group of 51 patients with extremity injury, the range of trauma injuries in V005 were broad, including penetrating trauma cases and blunt injury cases.

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

The 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.

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

30-Day Endpoint V005 Trial

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

Primary Patency 84.3% Not reported

Secondary Patency 90.2% 78.9%

Conduit Infections 2.0% 8.4%

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)

Number of Patients (%)

Total Adverse Events 50 (98.0%)

Non-Fatal Serious Adverse Events 28 (54.9%)

Over Duration of Study

HAV Infections 2 (3.9%)

HAV Rupture 1 (2.0%)

HAV Occlusion/Thrombosis 15 (29.4%)

Pseudoaneurysm 1 (2.0%)

Aneurysm 1 (2.0%)

Other 2 (3.9%)

There were no unexpected safety signals for the 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.

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.

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.

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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 have utilized the HAV to treat patients with wartime injuries including blast trauma, shrapnel injuries, and gunshot wounds.

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.

As of December 31, 2022, a total of ten vascular patients have been treated under this humanitarian program, and all patients are reported to have primary patency at 30 days and zero cases of infection despite the presence of contaminated wound beds.

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.

The FDA advised Humacyte to include in the BLA submission patient outcomes from the Ukraine humanitarian program.

We refer to the results for the 16 patients from Ukraine with extremity vascular trauma who provided consent for use of their results in the BLA filing as the V017 trial.

A high success rate for the 16 extremity patients in the V017 trial was observed, despite the presence of contaminated wound beds, as summarized in the table below.

V017 Ukraine Humanitarian HAV Results in Vascular Trauma

30-Day Endpoint V017 Trial

HAV Extremity Group (%)

Primary Patency 93.8%

Secondary Patency 93.8%

Conduit Infections 0.0%

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)

Number of Patients (%)

Total Adverse Events 4 (25.0%)

Non-Fatal Serious Adverse Events 1 (6.3%)

Over Duration of Study

HAV Infections 0 (0.0%)

HAV Rupture* 1 (6.3%)

HAV Occlusion/Thrombosis 1 (6.3%)

Pseudoaneurysm 0 (0.0%)

Aneurysm 0 (0.0%)

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

In the figure below, photographs are shown of the first patient treated under the humanitarian program in Ukraine.

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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

Compared to Synthetic Graft Benchmark

30-Day Endpoint V005 Trial

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

Secondary Patency 91.5% 78.9%

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.

Proposed Indication #2:

Use of the HAV for Arteriovenous Access for Hemodialysis

Overview of Hemodialysis and Existing Methods of Arteriovenous Access for Hemodialysis

Use of the HAV for AV Access for Hemodialysis

Overview of Hemodialysis and Existing Methods of AV Access for Hemodialysis

End-stage renal disease (“ESRD”) develops when chronic kidney disease progresses to a point where either dialysis or a kidney transplant is required for the patient to survive.

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

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

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

12‑month SP HAV:

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Number of HAV Rejections:

V007 Dialysis Access 2017 Phase 3 Prospective Randomized Blinded Target 240 total;

230 enrolled (as of December 31, 2022) Enrolling Trial is currently enrolling

V011 Dialysis Access 2019 Phase 2 (LUNA200 manufacturing system) 30 3‑year follow-up ongoing 30‑day PP:

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

___________________________

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Phase 3 V006 HUMANITY trial rates of infection

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

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.

SAEs Reported in V006 Phase 3 Clinical Study in AV Access

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Trial Design:

We are currently enrolling a Phase 3 trial, called V007, in 240 patients with ESRD.

In April 2023 we completed enrollment of a Phase 3 trial, called V007, in 242 patients with ESRD.

V007 is a Phase 3, prospective, multi-center, open label, randomized, two-arm comparative study conducted in the United States.

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Current Trial Status:

As of December 31, 2022, there were 230 patients enrolled in the V007 trial, out of a target enrollment of 240 total.

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

As of December 31, 2023, 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

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 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.

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 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.

Proposed Indication #3:

Peripheral Artery Disease

PAD involves partial or complete occlusion of blood vessels in the peripheral circulation and is a major cause of morbidity and mortality in the developed world.

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

Peripheral Artery Disease Saphenous Vein (autologous) 2008 60 12 months:

Saphenous Vein (autologous) 2008 60 12 months:

– 86% N/A N/A

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Number of Rejections:

V004 Peripheral 2016 Phase 2 15 5-year 30-day PP:

Artery Disease Single-arm follow-up 6-month SP:

ongoing 12-month SP:

V004 Peripheral 2016 Phase 2 15 Completed 30-day PP:

Artery Disease Single-arm 6-month SP:

Infection Rate/yr:

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Trial Design:

Both our V004 and V002 trials are prospective, open-label, single treatment arm, multi-center studies.

Both our V004 and V002 trials were prospective, open-label, single treatment arm, multi-center studies.

We enrolled 20 patients in our V002 trial in Poland, and 15 patients in our V004 trial in the United States.

Both trials have the primary objectives of evaluating the safety of the HAV as a femoral-to-popliteal bypass graft, and determining the primary, primary assisted, and secondary patency over 12 and 24 months.

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.

Current Trial Status and Outcomes:

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

For Rutherford 4,5 patients with no vein and no revascularization procedure, amputation rates at 6 months are reported at 31%.

For stage 4,5 patients who do undergo saphenous vein revascularization, the amputation rate at one year is approximately 10%.

The lack of amputation for stage 4,5 patients in the V004 trial at one year, none of whom had saphenous vein for revascularization, supports the use of the HAV in severe PAD.

For Rutherford 4 and 5 patients with no vein and no revascularization procedure, amputation rates at 6 months are reported at 31%.

For stage 4 and 5 patients who do undergo saphenous vein revascularization, the amputation rate at one year is approximately 10%.

The lack of amputation for stage 4 and 5 patients in the V004 trial at one year, none of whom had saphenous vein for revascularization, supports the use of the HAV in severe PAD.

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

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He underwent a successful bypass with the HAV.

Imaging at one year demonstrated a patent graft.

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

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Mayo Clinic Study in Severe PAD

The Mayo Clinic, Rochester, MN, is conducting a study in up to 25 patients with severe PAD under an investigator IND filed with the FDA.

As of December 25, 2022, 18 patients have been implanted with the HAV under the study.

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.

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.

Of these 29 patients, 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%.

The limb salvage rate was 86%, corresponding to only a 14% amputation rate.

Preclinical Pipeline

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Furthermore, we have implanted rat-sized BVPs into the aortas of diabetic rats, and observed that the BVP could restore normal glucose levels in all treated animals, while control animals (“No Flow” in red in figure below) did not restore glucose control.

Studies in large animal models are planned to commence in 2023 as the next step in the development of this product candidate.

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.

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)

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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 plan to commence IND-enabling preclinical studies in large animals to support potential advancement of the HAV into human clinical trials.

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

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BT Shunt Implant Schematic

In November 2021, the results for this preclinical study were presented at the American Heart Association’s Scientific Sessions 2021 meeting.

In this study, five non-immunosuppressed juvenile primates were surgically implanted with the 3.5mm diameter HAVs as mBTT shunts.

The 3.5mm HAVs were implanted into primates as mBTT shunts using standard surgical techniques, and the animals were studied for three to six months.

Each of the HAVs remained parent during the study and exhibited repopulation with vascular cells.

Two of the primates showed a stronger xenogeneic to the human HAV material.

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.

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We source bioprocess solutions, including culture media and decellularization buffers, from a division of Thermo Fisher Scientific, which has a second production site to provide redundant media/buffer production capacity.

We are in the process of developing redundant vendors for all critical materials and we manage all vendor changes through a robust change control process.

We continue to explore the development redundant vendors for all critical materials and we manage all vendor changes through a robust change control process.

Supply Agreement with SeraCare

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

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

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 peripheral artery disease, and the treatment of vascular trauma, but excluding coronary artery bypass graft, pediatric heart surgery, or adhering pancreatic islet cells onto the outer surface of the distribution product for use in diabetic patients.

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.

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.

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For countries outside the United States, the parties agreed to use commercially reasonable efforts to satisfy certain agreed minimum market entry criteria for the distribution product in the field in such country.

For the EU, once such criteria have been satisfied for the applicable country, or if the parties otherwise mutually agree to obtain regulatory

approval for the distribution product in the field in the applicable country, we agreed to use commercially reasonable efforts to obtain such regulatory approval (other than pricing approval), and Fresenius Medical Care agreed to use commercially reasonable efforts to obtain the corresponding pricing approval.

For the EU, once such criteria have been satisfied for the applicable country, or if the parties otherwise mutually agree to obtain regulatory approval for the distribution product in the field in the applicable country, we agreed to use commercially reasonable efforts to obtain such regulatory approval (other than pricing approval), and Fresenius Medical Care agreed to use commercially reasonable efforts to obtain the corresponding pricing approval.

For the rest of the world (i.e., outside the United States and the EU), once such criteria have been satisfied for the applicable country, or if the parties otherwise mutually agree to obtain regulatory and pricing approval for the distribution product in the field in the applicable country, Fresenius Medical Care agreed to use commercially reasonable efforts to obtain such approvals, and we agreed to use commercially reasonable efforts to support Fresenius Medical Care in its efforts.

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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.

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Our 18 families of patents are comprised of:

(i) eight issued U.S.

patents, 74 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, nine pending U.S.

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

(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,

(ii) three issued U.S.

patents, 19 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 two pending foreign patent applications in Europe and Canada, which we co-own, and

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

(iii) one issued U.S.

patents, seven issued foreign patents in Canada, France, Germany, Italy, Spain, Sweden, and the UK, one pending 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.

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patents relating to the systems and methods of manufacturing our vessels expires in 2032.

patent relating to the entangler machinery used to make tubular

scaffolds expires in 2035.

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

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.

If these non-provisional applications are allowed, such additional patents issuing therefrom would be expected to expire around 2043.

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We have also registered trademarks for use in connection with our products.

These include registrations for HUMACYL™ in the United States, Europe, Australia, Canada, China, and Israel;

These include registrations for SYMVESS™ in the United States, Europe, United Kingdom and Ukraine, HUMACYL™ in the United States, Europe, Australia, Canada, China, and Israel;

HUMAGRAFT™ in Australia, China, Europe, and Israel;

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We have agreed to indemnify Yale against certain third-party claims.

Small Diameter HAV Coating

In February 2014, we entered into a license agreement with Yale that granted us a worldwide license to the patents related to coatings for small-diameter vessels to inhibit clotting.

The license granted under the agreement is exclusive in the field of engineered vascular tissues and tissues and extracellular matrix-based implants used for vascular repair, reconstruction and replacement (provided that all uses are vascular tissues within the range of 1-12mm in diameter), except that it is subject to Yale’s non-exclusive right, on behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes.

We have agreed to use reasonable commercial efforts to develop and commercialize the licensed patents and any licensed products and methods, and to use reasonable efforts to make the licensed products available to patients in low and low-middle income countries.

We are also obligated to provide Yale periodically an updated and revised copy of our plan, which must indicate progress of our development and commercialization.

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

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

We have also agreed to pay to Yale:

an annual maintenance fee, increasing between the first anniversary of the agreement until the fifth anniversary up to a maximum of less than $0.1 million per year;

milestone payments upon

achievement of certain regulatory and commercial milestones of $0.2 million and $0.6 million for this license;

a low single-digit percentage royalty on worldwide net sales, subject to reductions for third-party license fees;

and a low double-digit percentage of sublicensing income.

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

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

Issued patents and additional patents issuing from this licensed portfolio will expire no earlier than 2034, and the term of each patent may be extended by patent term adjustment, patent term extension, or foreign equivalents thereof.

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

however, any such termination right would be limited in scope to the country or countries to which such failure relates.

Yale may also terminate for our non-payment, uncured material breach, failure to obtain adequate insurance, bringing or assisting in bringing of a patent challenge against Yale, abandonment of the research and development of our product or insolvency.

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

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.

Under certain circumstances, Yale may, at its option, convert the exclusive license to a non-exclusive license if we decline to initiate certain infringement or interference proceedings with respect to the licensed patents.

We have agreed to indemnify Yale against certain third-party claims.

On December 21, 2022, we provided notice to Yale that we were terminating the license effective March 21, 2023 as we do not intend to use the technology underlying the patents.

Biovascular Pancreas

In August 2019, we entered into a license agreement with Yale that granted us a worldwide license to its patents related to a biovascular pancreas.

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.

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however, any such termination right would be limited in scope to the

country or countries to which such failure relates.

however, any such termination right would be limited in scope to the country or countries to which such failure relates.

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Biologics require the submission of a BLA and approval by the FDA before being marketed in the United States.

None of our vessels have been approved by the FDA for marketing in the United States, and we currently have no BLAs pending.

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

If we fail to comply with applicable FDA or other requirements at any time during the product development process, clinical testing, and the approval process or after approval, we may become subject to administrative or judicial sanctions.

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Before a biologic is approved in the United States, an applicant must submit a BLA that includes sufficient evidence to establish the safety, purity, and potency of the product candidate for its intended indications, including from the results of preclinical studies and clinical trials.

A BLA must also contain extensive information about manufacturing and product quality control testing, and the applicant must pass an FDA preapproval inspection of the manufacturing facility or facilities at which the biologic product is produced and distributed from to assess compliance with current good manufacturing practices, or cGMPs.

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

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

For Humacyte’s development of product candidates, Phase 1 and Phase 2 trials have heretofore been combined into a single trial design.

For certain of Humacyte’s development of product candidates, Phase 1 and Phase 2 trials have heretofore been combined into a single trial design.

The biological product is initially introduced into human subjects and tested for safety.

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After the BLA submission is accepted for filing, the FDA reviews the BLA to determine, among other things, whether the proposed product is safe and potent, or effective, for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMPs (and, where applicable, GTPs) to assure and preserve the product’s identity, safety, strength, quality, potency, and purity, and biological product standards.

The FDA may refer applications for novel biological products or biological

products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes outside clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and, if so, under what conditions.

The FDA may refer applications for novel biological products or biological products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes outside clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and, if so, under what conditions.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

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The sponsor of a Fast Track product has opportunities for more frequent interactions with the applicable FDA review team during product development and, once a BLA is submitted, the product candidate may be eligible for priority review.

determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.

A Fast Track product may also be eligible for rolling review, where the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.

A biological product candidate may be eligible for Breakthrough Therapy Designation if it is intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

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The results of the clinical trial must be submitted to the competent authorities and, with the exception of non-pediatric Phase 1 trials, will be made public at the latest within 12 months after the end of the trial.

During the development of a medicinal product, the European Medicines Agency (“EMA”) and national medicines regulators within the EU provide the opportunity for dialogue and guidance on the development program.

During the development of a medicinal product, the EMA and national medicines regulators within the EU provide the opportunity for dialogue and guidance on the development program.

At the EMA level, this is usually done in the form of scientific advice, which is given by the Scientific Advice Working Party of the Committee for Medicinal Products for Human Use (“CHMP”).

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All application procedures require an application in the common technical document format, which includes the submission of detailed information about the manufacturing and quality of the product, and non-clinical and clinical trial information.

There is an increasing trend in the EU towards greater transparency and, while the manufacturing or quality information is currently generally protected as confidential information, the EMA and national regulatory authorities are now liable to disclose much of the non-clinical and clinical information in marketing authorization dossiers, including the full clinical study reports, in response to freedom of information requests after the marketing authorization has been granted.

There is an increasing trend in the EU towards greater transparency and, while the manufacturing or quality information is currently generally protected as confidential information, the EMA and national regulatory authorities are now liable to disclose much of the non-clinical and clinical information in marketing authorization dossiers, including the full clinical study reports, proactively or in response to freedom of information requests after the marketing authorization has been granted.

The centralized procedure gives rise to marketing authorizations that are valid throughout the EU.

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The EMA forwards CHMP opinions to the European Commission, which uses them as the basis for deciding whether to grant a marketing authorization.

The centralized procedure is compulsory for medicinal products that (1) are derived from biotechnology processes, (2) contain a new active substance (not yet approved on 20 November 2005) indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders, viral diseases or autoimmune diseases and other immune dysfunctions, (3) are orphan medicinal products or (4) are advanced therapy medicinal products.

For medicines that do not fall within these categories, an applicant may voluntarily submit an application for a centralized marketing authorization to the EMA, as long as the CHMP agrees that (i) the medicine concerned contains a new active substance (not yet approved on November 20, 2005), (ii) the medicine is a significant therapeutic, scientific, or technical innovation, or if its authorization under the centralized procedure would be in the interest of public health.

The centralized procedure is compulsory for medicinal products that (1) are derived from biotechnology processes, (2) contain a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative disorders, viral diseases or autoimmune diseases and other immune dysfunctions, (3) are orphan medicinal products or (4) are advanced therapy medicinal products.

For medicines that do not fall within these categories, an applicant may voluntarily submit an application for a centralized marketing authorization to the EMA, as long as the CHMP agrees that (i) the medicine concerned contains a new active substance, (ii) the medicine is a significant therapeutic, scientific, or technical innovation, or if its authorization under the centralized procedure would be in the interest of public health.

For those medicinal products for which the centralized procedure is not available, the applicant must submit marketing authorization applications to the national medicines regulators through one of three procedures:

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Conformity assessment procedures for all but the lowest risk classification of device involve a notified body, which are non-governmental, private entities licensed to provide independent certification of certain classes of medical device.

EU regulatory bodies are not involved in the premarket approval of medical devices, with only very limited exceptions (such as medical devices that incorporate a medicinal product as an ancillary substance, in which case these regulatory bodies

review the medicinal product).

The onus of ensuring a device is safe enough to be placed on the market is ultimately the responsibility of the manufacturer and the notified body.

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Employees and Human Capital Management

As of December 31, 2022, we had 164 employees that were all full-time.

As of December 31, 2023, we had 185 employees, of which 183 were full-time.

None of our employees are represented by a collective bargaining agreement, and we have never experienced any work stoppage.

We believe we have good relations with our employees.

Financing Arrangements

In March 2021, Legacy Humacyte entered into a Loan Agreement with Silicon Valley Bank and SVB Innovation Credit Fund VIII, L.P., which provides a term loan facility of up to $50.0 million with a maturity date of March 1, 2025.

We became a co-borrower under the Loan Agreement in connection with the Merger.

The obligations of Humacyte and Legacy Humacyte under the Loan Agreement are secured by substantially all of their assets, except for their intellectual property.

In connection with the Loan Agreement, the lenders were each granted a warrant to purchase Legacy Humacyte common stock, with an exercise price of $2.699 per share, subject to customary adjustments.

In connection with the closing of the Merger, these warrants were exchanged for warrants to purchase 287,704 shares of our common stock at an exercise price of $10.28 per share.

On October 13, 2021, we borrowed an additional $10.0 million under the Loan Agreement, and in connection with that borrowing, issued Silicon Valley Bank and SVB Innovation Credit Fund VIII, L.P.

warrants to purchase an aggregate of 123,302 shares of our common stock at an exercise price of $10.28 per share.

The Loan Agreement contains certain customary covenants, including, but not limited to, those relating to additional indebtedness, liens, asset divestitures, and affiliate transactions.

We may use the proceeds of borrowings under the Loan Agreement as working capital and to fund our general business requirements.

As of February 28, 2023, we had borrowed $30.0 million of principal under the Loan Agreement.

Additional Information

We were incorporated in Delaware on July 1, 2020, under the name Alpha Healthcare Acquisition Corp.

(“AHAC”), in order to effectuate a merger, capital stock exchange, asset acquisition, stock purchase, reorganization or similar business combination with one or more businesses or entities.

in order to effectuate a merger, capital stock exchange, asset acquisition, stock purchase, reorganization or similar business combination with one or more businesses or entities.

AHAC completed its initial public offering on September 22, 2020.

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The information posted on our website is not incorporated into this Annual Report on Form 10-K.

Securities and Exchange Commission (“SEC”) maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC at http://www.sec.gov.

Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Securities Exchange Act of 1934, as amended, (the “Exchange Act”) are also available free of charge on our investor relations website as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

SEC maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC at http://www.sec.gov.

Our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act are also available free of charge on our investor relations website as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

We provide notifications of news or announcements regarding our financial performance, including SEC filings, investor events, and press releases, as part of our investor relations website.

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

What changed 10-K

Item 1. Business