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Item 1. Business

2023-03-24 compared with 2022-03-29 · 163 added, 143 removed, 1212 unchanged (20% of the section changed)

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Humacyte, Inc.

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

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

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.

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, or HAVs.

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.

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arteriovenous (“AV”) access for hemodialysis;

peripheral arterial disease (“PAD”);

peripheral artery disease (“PAD”);

and coronary artery bypass grafting (“CABG”).

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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.

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, 2022, our HAVs have been implanted in approximately 533 patients.

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

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

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

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

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.

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

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

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

• 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.

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

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

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.

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.

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

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

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 used in our Phase III trials.

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

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

The results of the comparability assessment and the 30-day results from the V011 crossover study were submitted to the FDA.

In 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.

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

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

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

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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 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 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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Our Market Opportunity

We are a biotechnology company with Phase III clinical trials in two indications and a strong pipeline for additional products and indications.

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.

Our Initial Market Opportunity in Vascular Repair, Reconstruction and Replacement

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

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

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In military populations, as the rate of battlefield fatalities has been declining due to faster evacuations and more robust protection from body armor, the rate of survivable vascular injuries has been increasing.

In civilian populations, trauma injuries are primarily caused by motor vehicle accidents, gun violence, mass casualty terrorist attacks, stabbings and blunt trauma.

In civilian populations, trauma injuries are primarily caused by motor vehicle, workplace and sporting accidents, gun violence, mass casualty terrorist attacks, stabbings, blunt trauma, and iatrogenic injuries (injuries caused by medical treatment or examination).

We estimate that central or peripheral vascular injuries in civilian patients account for approximately 150,000 of all injuries reported in global trauma patients.

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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.

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 :

An estimated $5 to $6 billion per year is spent on hospital admissions in hemodialysis patients with infection and access complications.

In 2017, there were nearly 500,000 patients receiving hemodialysis in the United States.

In 2021, there were over 550,000 patients receiving hemodialysis in the United States.

Annually, at least 160,000 existing or new dialysis patients require a new AV access in the U.S.

and an additional 150,000 patients require a new AV access in Europe and Japan.

Hemodialysis patients are a chronically ill patient population, suffering an average of 1.8 hospital admissions, three visits to the emergency department, and four days hospitalized for infections each year.

The two most common causes of hospital admissions in hemodialysis patients are infection and access complications, resulting in an estimated total spend of $5 billion to $6 billion per year.

For hemodialysis patients, an infected access can lead to sepsis, which is life threatening, is the most expensive cause for hospitalization in the United States and carries at least a 10% overall mortality rate.

Hemodialysis patients are a chronically ill population, suffering an average of 1.8 hospital admissions, three visits to the emergency department, and four days hospitalized for infections each year.

The two most common causes of hospital admissions in hemodialysis patients are infection and access complications.

For hemodialysis patients, an infected access site can lead to sepsis, a life-threatening complication that is the most expensive cause for hospitalization in the United States and carries at least a 10% overall mortality rate.

We believe that our 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.

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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 heart to head, arms, kidneys, and stomach.

We believe our

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

Peripheral arterial bypass procedures are common with as many as 160,000 PAD related procedures reported annually in the U.S.

and over 550,000 annual PAD procedures estimated globally.

Expanding into markets outside the U.S., annual peripheral bypass procedures are nearly 170,000 per year in Europe, and approximately 220,000 per year in Asia.

While endovascular techniques have become available over the past ten years to treat an array of vascular occlusions, depending on the nature and length of the blockage these types of treatment options have met with both mixed success and durability compared to conventional surgical bypass.

Both angioplasty and stenting procedures provide near term success, however long-term durability has remained a question.

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.

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.

Both angioplasty and stenting procedures provide near term success, however long-term durability has remained a question, as highlighted in the results of the recent BEST-CLI clinical trial published in the New England Journal of Medicine demonstrating that patients treated with surgical bypass had fewer major amputations and less need for repeat procedures than those treated with endovascular therapy.

Type I Diabetes :

Type 1 diabetes, caused by auto-immune destruction of insulin-producing cells in the islets of the pancreas, is a devastating disease affecting more than 1.7 million people in the United States, and costing at least $10 billion to $14 billion annually.

In Europe, the number of patients suffering with Type 1 diabetes is estimated at approximately 2.2 million.

In the EU4 (France, Germany, Italy and Spain) and the UK, the number of patients suffering with Type 1 diabetes is estimated at approximately 1.5 million.

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

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

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

Studies in non-human primates are planned.

We 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.

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

CABG procedures are common, with 350,000 CABG procedures reported annually in the U.S.

CABG procedures are common, with more than 200,000 CABG procedures reported annually in the U.S.

and over 765,000 annual CABG procedures globally.

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The following table highlights key information about our current product pipeline:

We began clinical evaluations of our HAVs in December 2012, with the enrollment of the first Phase II patient in our V001 hemodialysis access trial in Europe.

Since then, we have completed one Phase II trial in the United States, and currently have seven trials either actively enrolling or in long-term follow-up.

HAVs have been implanted in approximately 79 clinical centers in six countries around the world, and by more than 100 practicing surgeons.

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.

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

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Vascular Trauma

V005 Vascular Trauma 2018 Phase II/III Single-arm Historical Comparator Unblinded Targeting 75± total 47 total (32 lower extremity) enrolled as of December 31, 2021 Enrolling Trial is currently enrolling

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

Dialysis Access

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

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

Infection Rate/yr:

Number of Rejections:

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

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

Infection Rate/yr:

Number of Rejections:

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

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:

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Number of HAV Rejections:

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

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 II (LUNA200 manufacturing system) 30 3-year follow-up ongoing 30-day PP:

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

Infection Rate HAV/yr:

Number of HAV Rejections:

Peripheral Arterial Disease

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

Peripheral Artery Disease

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

Infection Rate/yr:

Number of Rejections:

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

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

Infection Rate/yr:

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Our cumulative HAV exposure is approximately 880 subject-years in the hemodialysis access population, 130 subject-years in the PAD population, and 70 subject-years in the arterial trauma population.

The longest our HAV has been in a patient and used for dialysis is more than eight years and there have been more than 100,000 estimated dialysis

sessions using our HAVs.

Additionally, a total of 17 expanded access/compassionate use cases have been granted by the FDA.

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

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.

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.

We have also observed consistent durability with a strong tolerability profile.

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

The HAV has been implanted in approximately 471 patients, across approximately 79 clinical sites in six countries, over more than eight years (as of December 31, 2021).

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).

Rates of primary and secondary patency were similar across trial designs and disease states, with 30-day primary patency ranging from 95% – 100%.

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

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

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.

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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HAVs Remodel with Host Cells After Implantation

Additionally, based on clinical samples obtained during our Phase II AV access trials and published in three peer reviewed journals, The Lancet in 2016, Science Translational Medicine in 2019, and in the Journal of Vascular Surgery in 2020, we observed that the HAV became populated with healthy, vascular cells from the patient.

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.

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3.2% 5.3% N/A

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

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

ePTFE (synthetic graft) 2008 61 12 months:

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In civilian populations, trauma injuries are primarily caused by motor vehicle accidents, gun violence, mass casualty terrorist attacks, stabbings and blunt trauma.

In civilian populations, trauma injuries are primarily caused by motor vehicle, workplace and sporting accidents, gun violence, mass casualty terrorist attacks, stabbings, blunt trauma and iatrogenic injuries (injuries caused by medical treatment or examination).

Consequently, we believe there is an increasingly urgent unmet need for novel materials that are immediately available for permanent vascular repair for both civilian and military vascular trauma.

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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 II/III Trial for Vascular Trauma

Our Current Phase 2/3 Trial for Vascular Trauma

Trial Design:

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

The current primary efficacy endpoint evaluates primary patency of the HAV at 30 days.

Based on the results we have observed to date, and subject to discussions with the FDA regarding trial size, we expect that the final design of the trial will support the submission of a BLA in 2022 or 2023.

We anticipate that analysis of data from V005 will focus on patients with lower extremity injuries.

The final number of subjects to be enrolled and evaluated in the study is dependent on additional guidance from the FDA, but is currently estimated to approximate 75.

Status of Phase III Trial of HAV in Vascular Trauma (as of December 31, 2021)

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.

Status of Phase 3 Trial of HAV in Vascular Trauma (as of December 31, 2022)

Number Indication Begin

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

___________________________

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Current Trial Status:

During 2020, we increased the number of trial sites for the V005 trial in the United States, from seven to 20 sites.

We are currently working to further expand sites in the United States, as well as add additional sites in Poland and Israel.

Increasing the number of sites is expected to provide a broader patient cohort for enrollment in the trial, providing more extensive clinical exposure to differing types of vascular traumatic injury.

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.

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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).

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.

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

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.

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.

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.

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

The patient was a 42-year-old male who suffered a gunshot wound in the leg which damaged his femoral artery.

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

The 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.

Proposed Indication #2:

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A catheter, which is tunneled underneath the skin and placed directly into a large vein in the patient, is generally the least desirable access solution.

Given the time necessary for fistulae to mature, the vast majority of patients in

the United States begin hemodialysis using a catheter while awaiting fistula maturation.

Given the time necessary for fistulae to mature, the vast majority of patients in the United States begin hemodialysis using a catheter while awaiting fistula maturation.

Catheters have rates of blood stream infections as high as 200% per patient-year, with high associated morbidity and health care costs.

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

Our Current Phase II and Phase III Trials of the HAV in Hemodialysis Access

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

Clinical Trial

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Subjects Status Outcomes**

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

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

Infection Rate/yr:

Number of Rejections:

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

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

Infection Rate/yr:

Number of Rejections:

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

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:

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Number of HAV Rejections:

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

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 II (LUNA200 manufacturing system) 30 3‑year follow-up ongoing 30‑day PP:

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

Infection Rate HAV/yr:

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patent with or without interventions.

Long-Term Data from Early Phase II Trials in Hemodialysis:

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

V001 and V003

Phase II Trial Design and Current Outcomes:

We have completed or are in long-term follow-up on two open-label Phase II trials in 60 hemodialysis patients in the United States and Poland from December 2012 through May 2014, which we refer to as our V003 trial and V001 trial, respectively.

Phase 2 Trial Design and Current Outcomes:

We have completed or are in long-term follow-up on two open-label Phase 2 trials in 60 hemodialysis patients in the United States and Poland from December 2012 through May 2014, which we refer to as our V003 trial and V001 trial, respectively.

Both the V001 and V003 studies were designed as single-arm trials to assess the safety and efficacy of the HAV for hemodialysis access, with assessments of patency at 6, 12, 18 and 24 months.

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

Phase III V006 AV Access Study

Phase 3 V006 AV Access Study

Trial Design:

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

SAEs Reported in V006 Phase III Clinical Study in AV Access

SAEs Reported in V006 Phase 3 Clinical Study in AV Access

Description of SAE Number of SAEs

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

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

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);

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

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

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.

This outcome was due at least in part to unexpectedly high patency of the ePTFE grafts, particularly after 12 months.

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

Phase III V007 AV Access Study

Phase 3 V007 AV Access Study

Trial Design:

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

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

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

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

The V007 trial is designed to assess the usability of the 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.

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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 to complete the V007 trial in time to support a BLA filing for the use of HAV in AV access for hemodialysis in 2023.

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

Proposed Indication #3:

Peripheral Arterial Disease

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 Arterial Disease Saphenous Vein (autologous) 2008 60 12 months:

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

– 86% N/A N/A

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

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

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

Our Current Phase II Trials of the HAV in PAD

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

Number Indication Begin

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Subjects Status Outcomes**

V002 Peripheral 2013 Phase II 20 10-year 30-day PP:

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

V002 Peripheral 2013 Phase 2 20 10-year 30-day PP:

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

ongoing 12-month SP:

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Number of Rejections:

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

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

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

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

ongoing 12-month SP:

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Patients in the V002 trial are currently in long-term follow-up out to ten years.

For the V002 trial, six-year long-term follow-up data were compiled in March 2021, which confirmed durability of the HAV in the arterial circulation.

For HAV patients in the V002 trial, there were also no reports of conduit infections, and no reports of amputations of the operative limb.

Long-term results from V002 Phase II study in PAD

In 2022, s ix-year results from V002 were published in Journal of Vascular Surgery – Vascular Science .

The article, entitled “6-Year Outcomes of a Phase 2 Study of Human-Tissue Engineered Blood Vessels for Peripheral Arterial Bypass,” reported overall secondary patency rate of 60% at 72 months, including all patients originally enrolled, as estimated by Kaplan Meier analysis.

There was no evidence of graft rejection or infection, and no patients underwent amputation of the affected limb out to six years.

Long-term results from V002 Phase 2 study in PAD

Result from V002

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Hence, the subjects enrolled in the V004 trial had severe and debilitating limb ischemia due to PAD and had no autologous vein that was suitable for lesion bypass and revascularization.

12-month results from V004 Phase II study in PAD

12-month results from V004 Phase 2 study in PAD

Result from V004 Trial (as of April 2021)

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Lastly, there were zero reported amputations of any operative limb in the first 12 months of follow-up.

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

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

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

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The patient had no signs of infection in the HAV 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 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.

Preclinical Pipeline

Pancreatic Islet Transplantation for Type 1 Diabetes (“Biovascular Pancreas”)

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

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.

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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 as the next step in the development of this product candidate.

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

Coronary Artery Bypass Graft (CABG)

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

We anticipate that this study will provide sufficient in vivo data to support an IND filing for a Phase I clinical trial in adult CABG.

As of December 31, 2021, we have implanted a 3.5mm HAV CABG from the aorta to the left anterior descending coronary artery in five baboons.

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

In January 2022, results from this preclinical study were presented at Advanced Therapies Week where we reported that the HAV maintained patency and exhibited host-cell remodeling and regeneration in the non-human primate model.

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

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

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The system used in our clinical trials since 2016, including all Phase III trials, utilizes a single tray within one growth drawer holding ten HAVs per batch.

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.

This system is planned to be utilized for ongoing Phase III trials and for subsequent anticipated commercial launches once approved.

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.

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In this way, a single LUNA200 can produce up to 200 HAVs per batch while maintaining the critical operating parameters that direct growth, creating a gross capacity of approximately 900 HAVs per system annually.

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

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 used in our Phase III trials.

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

The results of the comparability assessment and the 30-day results from the V011 crossover study were submitted to the FDA.

In 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.

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Distribution Agreement with Fresenius Medical Care

We entered into a distribution agreement with Fresenius Medical Care in June 2018 which, as amended as of February 16, 2021, granted Fresenius Medical Care and its affiliates exclusive rights to develop outside the United States and European Union (the “EU”) and commercialize outside of the United States our 6 millimeter x 42cm HAV and all improvements thereto, and modifications and derivatives thereof (including any changes to the length, diameter or configuration of the foregoing), for use in vascular creation, repair, replacement or construction, including renal replacement therapy for dialysis access, the treatment of peripheral arterial disease, and the treatment of vascular trauma, but excluding coronary artery bypass graft, pediatric heart surgery, or adhering pancreatic islet cells onto the outer surface of the distribution product for use in diabetic patients.

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.

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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They may also be subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, any of which could harm our business, prospects, operating results and financial condition.

Containment of healthcare costs has been a priority of federal, state, and foreign governments, and the prices of drug products have been a focus of this effort.

Governments have shown significant interest in implementing cost-containment programs.

This interest has resulted in significant proposed and enacted reform measures affecting healthcare reimbursement and drug pricing, including the enactment in August 2022 of significant changes to potential Medicare drug product reimbursement through government negotiation of certain drug prices, as well as manufacturer discount and inflation rebate obligations under the Inflation Reduction Act (the “IRA”).

Intellectual Property

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As of December 31, 2022, our patent estate is comprised of 18 families of patents.

Of these families, nine are solely owned by Humacyte, one is jointly owned by Humacyte and Global Life Sciences Solutions USA LLC, one is jointly owned by Humacyte and Yale University, two are exclusively licensed to Humacyte from Duke University and two are exclusively licensed to Humacyte from Yale University.

Of these families, 14 are solely owned by Humacyte, one is jointly owned by Humacyte and Global Life Sciences Solutions USA LLC, one is jointly owned by Humacyte and Yale University, one is exclusively licensed to Humacyte from Duke University and one is exclusively licensed to Humacyte from Yale University.

For more information regarding these license agreements, see “— License Agreement with Duke University” and “— License Agreements with Yale University.”

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(i) eight issued U.S.

patents, 64 foreign patents in Austria, Belgium, Canada, China, Cyprus, Denmark, France, Germany, Hong Kong, Hungary, Ireland, Italy, Japan, Liechtenstein, Netherlands, Spain, Sweden, Switzerland, Turkey, and the UK, five pending U.S.

non-provisional patent applications, one pending PCT patent application and two pending foreign applications in Europe and Hong Kong, which are solely owned by us,

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,

(ii) three issued U.S.

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

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

(iii) two issued U.S.

patents, 23 issued foreign patents in Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Liechtenstein, Netherlands, Spain, Sweden, Switzerland, Turkey, and the UK, one pending U.S.

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

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

(iii) one issued U.S.

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

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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 three pending, Humacyte-owned non-provisional applications relating to the manufacturing of engineered tissues at commercial scale.

If these three non-provisional applications are allowed, such additional patents issuing therefrom would be expected to expire around 2040.

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.

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

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

However, our owned and licensed pending patent applications, and any patent

applications that we may in the future file or license from third parties, may not result in the issuance of patents.

However, our owned and licensed pending patent applications, and any patent applications that we may in the future file or license from third parties, may not result in the issuance of patents.

For more information, see “Risk Factors — Risks Related to Our Intellectual Property.”

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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.

behalf of itself and all other non-profit academic institutions, to use the licensed products for research, teaching, and other non-commercial purposes.

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

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

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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;

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;

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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

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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.

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.

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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.

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.

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The supply of cryopreserved vessels is limited by the number of cadaveric donors available, and the vessels are often non-uniform in size.

In addition, because the vessels contain human

cells from a donor, they can generate an immune rejection response that can lead to aneurismal degradation or catastrophic failure.

In addition, because the vessels contain human cells from a donor, they can generate an immune rejection response that can lead to aneurismal degradation or catastrophic failure.

Furthermore, development of antibodies to the implanted cryopreserved human vessel frequently has a detrimental impact on the ability of the patient to receive a transplant in the future.

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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 I and Phase II trials have heretofore been combined into a single trial design.

For the V005 trauma trial, we are in discussions with FDA about converting a Phase II/III study into a Phase III pivotal study.

For 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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These trials are designed to generate enough data to statistically evaluate clinical effectiveness and safety as well as to establish the overall benefit-risk relationship of the investigational new biological product, and to provide an adequate basis for product approval.

FDA typically requires at least two Phase III trials to support approval, but in some cases may approve an application on the basis of one trial.

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.

In some cases, the FDA may condition approval of a BLA on the sponsor’s agreement to conduct additional clinical trials to further assess the biologic’s safety and effectiveness after BLA approval.

Such post-approval clinical trials are typically referred to as Phase IV clinical trials.

Such post-approval clinical trials are typically referred to as Phase 4 clinical trials.

During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical trial investigators.

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

Breakthrough Therapy Designation provides all the features of Fast Track designation in addition to intensive guidance on an efficient development program beginning as early as Phase I, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where appropriate.

Breakthrough Therapy Designation provides all the features of Fast Track designation in addition to intensive guidance on an efficient development program beginning as early as Phase 1, and FDA organizational commitment to expedited development, including involvement of senior managers and experienced review staff in a cross-disciplinary review, where appropriate.

Any marketing application for a biological product submitted to the FDA for approval, including a product candidate with a Fast Track designation and/or Breakthrough Therapy Designation, may be eligible for other types of FDA programs intended to expedite the FDA review and approval process, such as priority review and accelerated approval.

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The sponsor of a clinical trial must register the clinical trial in advance, and certain information related to the clinical trial will be made public as part of the registration.

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

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.

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Employees and Human Capital Management

As of December 31, 2021, we had 146 employees, including 145 full-time employees.

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

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

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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