Humacyte, Inc. · NASDAQ:HUMA
Humacyte — Alpha Healthcare Acquisition — SPAC Merger (June 2021)
122 slides from Humacyte's SPAC merger presentation, Jun 7, 2021
Slide 1: Humacyte Incorporated June 2021 Investor Update
Humacyte Incorporated June 2021 Investor Update
Slide 2: Disclaimer
DISCLAIMER 2 These slides and the accompanying oral presentation contain forward - looking statements . All statements, other than statements of historical fact, included in these slides and the accompanying oral presentation are forward - looking statements reflecting management’s current beliefs a
Slide 3: Disclaimer: Important Information About the Merger
DISCLAIMER 3 Important Information About the Merger and Where to Find It A full description of the terms of the business combination is provided in a registration statement on Form S - 4 filed with the SEC by AHAC that includes a prospectus with respect to the securities to be issued in connection w
Slide 4: Agenda
AGENDA 4 Welcome Dr. Laura Niklason Scientific Platform Dr. Bob Langer Humacyte Clinical Overview Dr. Laura Niklason Vascular Trauma: Standard of Care Col. Todd Rasmussen Humacyte Innovation and Phase 2/3 Update Dr. Laura Niklason End Stage Renal Disease: Standard of Care Dr. Laura Niklason Humacyte
Slide 5: Humacyte Clinical Overview
Humacyte Clinical Overview Humacyte is pioneering the development and manufacture of off - the - shelf, universally implantable, bioengineered human tissues Dr. Laura Niklason
Slide 6: Key Features of Humacyte Technology
KEY FEATURES OF HUMACYTE TECHNOLOGY Potential benefits of HAVs evaluated in completed and ongoing clinical trials across multiple indications Off - the - shelf, immediately available with 18 - month shelf life HAV is highly resistant to infection No evidence of imm unogen i c it y Host cells repopul
Slide 7: Humacyte's R&D Pipeline
HUMACYTE’S R&D PIPELINE AIMED AT TREATING DISEASE THROUGHOUT THE BODY Vascular Products Tissue and Organ Products PRE - CLINICAL CLINICAL P R OG R AMS Vascular Trauma P er i phera l A r te r i al Disease (PAD) D i a l y si s A V A cc e ss Coronary Artery Bypass Graft (CABG) Lung T r a c hea Pancreas
Slide 8: Clinical-Stage Product Indications
8 CLINICAL - STAGE PRODUCT INDICATIONS Note: HAV data based on clinical trials to date Source: Humacyte Vascular Trauma • Restoring circulation quickly is key to good outcomes in acute trauma • HAVs are designed to be off - the - shelf and universally implantable • Phase 2/3 trial underway, single -
Slide 9: Extensive Clinical Experience in Varied Patient Cohorts
9 EXTENSIVE CLINICAL EXPERIENCE IN VARIED PATIENT COHORTS V 00 1 A V A cc e s s P ha s e 2 (60 - m ont h re s u l t s ) 2013 2014 2015 2016 2017 2018 2019 2020 HAVs have been implanted into hundreds of patients over more than 8 years. 2012 2021 A V Access Peripheral Arterial Disease T r au m a V005
Slide 10: Public Financing Expected to Facilitate Key Value-Creating Milestones
1 0 PUBLIC FINANCING EXPECTED TO FACILITATE KEY VALUE - CREATING MILESTONES • File BLA in Trauma 2022 • Submit for Marketing Approval in Trauma 2023 • PAD V004 2 - year Readout 2022 • Initiate Phase 3 PAD trial 2022 • V011 1 - year AV Results 2021 • V007 Finish Enrollment 2021 • V007 1 - year AV Res
Slide 11: HAV Maximal Pressures Resemble Those of Native Arteries
11 HAV MAXIMAL PRESSURES RESEMBLE THOSE OF NATIVE ARTERIES 1) Gomes, V.C. Journal of Vascular Surgery 2019 2) McClurken, M.E., Vascular Graft Update ASTM STP 898, 1986 3) Ciszek, B., Stroke 2013. 4) Dahl, et. Al., Science Translational Medicine, 2011 1,400 mmHg 1 1,800 mmHg 3 3 , 200 mm Hg 4 Synthet
Slide 12: HAV Is Highly Resistant to Infection
1 2 THE HAV IS HIGHLY RESISTANT TO INFECTION ACROSS ALL EVALUATED CLINICAL INDICATIONS 1) Zanoni, Journal of Vascular Access 2020 2) Vertrees, Infection and Critical Care, 2009 3) Siracuse, Journal of Vascular Surgery, 2013 4) PAD and Trauma Infection data as of April 2021 1.3% 0% 1.0% 4.5% 30% 1 HA
Slide 13: No Evidence of Immunologic Rejection
1 3 NO EVIDENCE OF IMMUNOLOGIC REJECTION AFTER IMPLANTATION IN ANY HUMACYTE PHASE 2 OR PHASE 3 STUDY • Panel Reactive Antibodies (PRAs) measure antibodies against donor organs. cPRA values range from 0 – 100%. • Patients with cPRA > 20% are considered “sensitized” and are difficult to cross - match
Slide 14: HAV Remodels as a Tissue Over Time
HAV REMODELS AS A TISSUE OVER TIME WHILE ePTFE SCARS AND FRACTURES WITH REPEATED CANNULATION 1 ePTFE: Patient V006 - 1167 - 001, 13 months HAV: Patient V006 - 1199 - 023, 13 months 14 1) Remodeling based on samples from clinical trials to date
Slide 15: The HAV Remodels With Patient Cells Over Time
THE HAV REMODELS WITH PATIENT CELLS OVER TIME 1 3079 - 012 - V006. 26 years old . 67.4 weeks post - implantation for AV Access 1006 - 001 - V006. 83 years old . 66.1 weeks post - implantation for AV Access 15 1) Remodeling based on samples from clinical trials to date
Slide 16: Overall Clinical Observations for HAV
OVERALL CLINICAL OBSERVATIONS FOR HAV • The HAV has been in clinical use since December 2012 , with over 800 patient - years of exposure to the product. • Patient exposure across 6 countries, in subjects ranging from 18 – 89 years of age, having multiple pre - existing co - morbidities. • The HAV ha
Slide 17: Platform Has Broad Application Across Multiple Diseases
HUMAYCTE PLATFORM HAS BROAD APPLICATION ACROSS MULTIPLE DISEASES Co r on ary Graft • CABG patients not always ideal for vein stripping: obesity, diabetes • HAVs are designed to be off - the - shelf and universal • 500,000 grafts per year in US Pediatric Heart Surgery • Babies born with heart defects
Slide 18: Todd E. Rasmussen: Need and Implications for Military and Civilian Trauma Care
Todd E. Rasmussen, MD, FACS Colonel, USAF MC Professor of Surgery The Uniformed Services University , Bethesda, Maryland Senior Associate Consultant in Vascular Surgery Mayo Clinic , Rochester, Minnesota Implementation of the Humacyte Human Acellular Vessel (HAV): Need and Implications for military
Slide 19: Military Need for Advanced Vascular Conduit
Military Need for Advanced Vascular Conduit TODD E. RASMUSSEN, MD, FACS Modern rate of vascular injury 5x that reported in previous wars Annals of Surgery 2011;253(6):1184 - 9 The Epidemiology of Vascular Injury in the Wars in Iraq and Afghanistan Joseph M. White, MD, Adam Stannard, MRC, Brian J. Ea
Slide 20: Military Need for Advanced Vascular Conduit
Military Need for Advanced Vascular Conduit TODD E. RASMUSSEN, MD, FACS Journal of Vascular Surgery 2018;68:1872 - 9 From the Society for Vascular Surgery A contemporary, 7 - year analysis of vascular injury from the war in Afghanistan Jigarkumar A. Patel, MD, Joseph M. White, MD, Paul W. White, MD,
Slide 21: Complex Wartime Injury
Complex Wartime Injury TODD E. RASMUSSEN, MD, FACS Right superficial femoral artery injury Traumatic left above knee amputation As such, saphenous vein not available for vascular repair 21
Slide 22: Complex Wartime Injury
Complex Wartime Injury TODD E. RASMUSSEN, MD, FACS Temporary vascular shunt placed in right superficial femoral artery Used ePTFE routed extra - anatomic to popliteal artery Graft became infected and extremity amputated 22
Slide 23: Complex Wartime Injury
Complex Wartime Injury TODD E. RASMUSSEN, MD, FACS Left proximal femoral artery injury with temporary vascular shunt Traumatic right above knee amputation Saphenous vein exposed as part of injury and used as repair conduit 23
Slide 24: Complex Wartime Injury
Complex Wartime Injury TODD E. RASMUSSEN, MD, FACS Repair of left superficial femoral artery and vein with saphenous taken from original wound Limb salvage particularly important as this patient had an above knee amputation of the other leg 24
Slide 25: Outcomes of US and UK Vascular Trauma
Outcomes of US and UK Vascular Trauma TODD E. RASMUSSEN, MD, FACS Journal of Vascular Surgery 2019 ; 70 : 224 - 232 Management and outcome of 597 wartime penetrating lower extremity arterial injuries from an international military cohort Anna E. Sharrock, MSc, MRCS, Nigel Tai, MS, FRCS, Zane Perkins
Slide 26: Outcomes of US and UK Vascular Trauma
Outcomes of US and UK Vascular Trauma TODD E. RASMUSSEN, MD, FACS Freedom from amputation was 74% at 5.5 years; better for gunshot wound than blast – likely due to severity of injury from blast mechanism 26
Slide 27: Humacyte HAV in Military Health System
Humacyte HAV in Military Health System TODD E. RASMUSSEN, MD, FACS Journal of Trauma & Acute Care Surgery 2019;87:S44 - S47 Clinical implementation of the Humacyte human acellular vessel: Implications for military and civilian trauma care 27 Jonathan J. Morrison, PhD, John McMahon, PhD, Joseph J. Du
Slide 28: HAV in Military & Civilian Health Systems
HAV in Military & Civilian Health Systems TODD E. RASMUSSEN, MD, FACS • Given promise of the HAV product, the military is leading the way with civilian expanded access cases • 5 cases at Walter Reed National Military Medical Center with military surgeons having performed 5 more at leading civilian c
Slide 29: HAV in Military & Civilian Health Systems
HAV in Military & Civilian Health Systems TODD E. RASMUSSEN, MD, FACS • Performance of anastomosis between HAV and the left common femoral artery 29 • Anastomosis is complete and arterial flow has been placed into the HAV which is now pulsatile and distended
Slide 30: HAV in Military & Civilian Health Systems
HAV in Military & Civilian Health Systems TODD E. RASMUSSEN, MD, FACS • Feeding the HAV into a metal tunneling device from the left groin to below the left knee 30 • Anastomosis complete to artery below the knee with restoration of arterial flow into the left leg and foot
Slide 31: Vascular Trauma Phase 2/3 V005 Trial
Vascular Trauma Phase 2/3 V005 Trial Dr. Laura Niklason
Slide 32: Vascular Trauma: The HAV May Save Lives and Limbs
3 2 VASCULAR TRAUMA: THE HAV MAY SAVE LIVES AND LIMBS 1) Alarhayem, A.Q., al, Journal of Vascular Surgery 2019; 69: 1519 - 1523. 2) Kauvar, D.S., et al, Journal of Vascular Surgery 2011; 53: 1598 - 603. 3) Siracuse, J.J. et al, Journal of Vascular Surgery 2013: 57: 700 - 705. 4) Andercou, O., et al,
Slide 33: Success Rates of Saphenous Vein and ePTFE Grafts in Trauma
3 3 SUCCESS RATES OF SAPHENOUS VEIN AND ePTFE GRAFTS IN TRAUMA 1) Klocker, Journal of Vascular Surgery , 2014 2) Watson, 2015 3) Vertres, Journal of Trauma , 2005 Saphenous Vein Success Rates ePTFE Success Rates 79% at 30 days 3 90% at 30 days 1 50% at 12 months 2 78% at 12 months 2
Slide 34: Time to Re-Vascularization Is Critical in Trauma Cases
3 4 TIME TO RE - VASCULARIZATION IS CRITICAL IN TRAUMA CASES 1) Alarhayem A.Q. et al, 2019; Journal of Vascular Surgery 2) Glass, G. et al. 2009; Journal of Plastic and Reconstructive Surgery. • In vascular trauma: quicker revascularization significantly reduces risk of amputation . 1 • Extending ti
Slide 35: Limb Salvage Is a Defense Department Priority
LIMB SALVAGE IS A DEFENSE DEPARTMENT PRIORITY • In 2018, the DoD listed Humacyte’s HAV as a Medical Product Priority under Public Law 115 - 92. • Public Law 115 - 92 requires enhanced collaborations and communication between the U.S. Department of Defense (DoD) and the U.S. Food and Drug Administrat
Slide 36: Ongoing Phase 2/3 V005 Trial in Vascular Trauma
ONGOING PHASE 2/3 V005 TRIAL IN VASCULAR TRAUMA Enrollment: Discussions with FDA are ongoing on final trial design (41 subjects enrolled through May 2021); Unblinded trial for repair of vascular traumatic injury. NCT03005418: A Study for the Evaluation of Safety and Efficacy of Humacyte’s Human Acel
Slide 37: HAV Performs Well Against Potential Comparators in V005 Trial
3 7 HAV PERFORMS WELL AGAINST POTENTIAL COMPARATORS IN V005 TRIAL Reported Outcome in PROOVIT PROOVIT (%) Primary Patency at 30 days ~ 79% NOT Complication Free, Patent at 30 days ~ 8% Required Intervention at Initial Hospitalization ~ 12% Potential Comparator 1 : Saphenous vein Data from PROspectiv
Slide 38: Subjects Enrolled in V005 Trauma Trial as of May 2021
3 8 SUBJECTS ENROLLED IN V005 TRAUMA TRIAL AS OF MAY 2021 Location of Injury Subjects Lower Extremity 29 Upper Extremity 9 Torso 3 Mechanism of Injury Subjects Gunshot Wound 18 Motor Vehicle Accident 6 Fall 4 Iatrogenic 11 I ndu s tr i a l A cc i den t/ C r u s h 2 41 Current HAV Implants for V005 I
Slide 39: Ongoing V005 Trial Shows Excellent Function to Date
3 9 I lia c Art e r y B y pa s s w i t h H AV ( Conne c t i n g pel v i s an d leg) ONGOING V005 TRIAL IN TRAUMA SHOWS EXCELLENT FUNCTION TO DATE Results to date show robust HAV function: Trauma Case Study ~14% ePTFE Infection Rate (Data from initial meta - analysis of published literature using ePT
Slide 40: Ongoing V005 Trial Shows Excellent Function to Date
4 0 ONGOING V005 TRIAL IN TRAUMA SHOWS EXCELLENT FUNCTION TO DATE • Sites are Level - I Trauma centers in the US, including sites with high clinical volume, led by key opinion leaders (e.g. Denver, Baltimore Shock - Trauma). • Outstanding HAV primary patency at 30 days: 97% as of May 2021. • Current
Slide 41: Vascular Trauma: Health Economics
4 1 VASCULAR TRAUMA – COMPELLING HEALTH ECONOMICS 1) Alarhayem, A.Q. et al, “Impact of time to repair on outcomes in patients with lower extremity arterial injuries”, Journal of Vascular Surger y 2019; 69: 1519 - 1523. 2) Kauvar, D.S., et al, “National trauma databank analysis of mortality and limb
Slide 42: Trauma Patients Receiving HAV After Saphenous Vein Graft Failure
SUBJECT 02 - 004 56 - year - old Female: • Received saphenous vein graft to restore flow after a serious car accident • Saphenous vein graft failed; Subject returned to operating room and received an HAV • Subject discharged from hospital with good blood flow to leg through HAV VASCULAR TRAUMA PATIE
Slide 43: Trauma Patients Receiving HAV After Saphenous Vein Graft Failure
VASCULAR TRAUMA PATIENTS RECEIVING HAV IN V005 TRIAL AFTER SAPHENOUS VEIN GRAFT FAILURE SUBJECT 06 - 013 57 - year - old Female: • Received saphenous vein graft to restore flow after dislocation of knee and artery injury due to a fall on ice • Saphenous vein graft failed; Subject transferred to anot
Slide 44: Expanded Use Case EA-013: Resists Infection
4 4 EXPANDED USE CASE # EA - 013: RESISTS INFECTION Source: Humacyte • The patient was a 38 - year - old female with critical limb ischemia due to systemic thromboembolic disorder that was treated with an autologous vein bypass • No vein was available to perform a bypass and the patient was at high
Slide 45: Milestones and Value Inflection Points for Trauma Program
4 5 MILESTONES AND VALUE INFLECTION POINTS FOR TRAUMA PROGRAM 2021 Complete agreement with FDA on number of subjects and comparator 2022 Completion of V005 Trauma trial enrollment, early top - line results Late - 2022 File BLA for Vascular Trauma , anticipate Accelerated Approval Pathway TARGET INDI
Slide 46: End Stage Renal Disease Standard of Care
End Stage Renal Disease Standard of Care Dr. Laura Niklason
Slide 47: End Stage Renal Disease Standard of Care
4 7 END STAGE RENAL DISEASE STANDARD OF CARE Leading Causes of ESRD in the US 2 : • Diabetes – 43% • Hypertension – 23% • Glomerulonephritis – 12% • Cystic Kidney Disease – 3% • Other – 19% 600k It is estimated that nearly 600,000 Americans suffer from End Stage Renal Disease (ESRD) 1 2 - 3% Rate of
Slide 48: US Statistics of ESRD Treatment
4 8 US STATISTICS OF ESRD TREATMENT TOTAL COST >$40 Billion (US) 1 12% of total expenditures are related to vascular access care (surgery, infections and interventions) Access care estimated to cost nearly $3 billion dollars (US, 2013) 2 MODE OF DIALYSIS CARE 92% Hemodialysis 1 8% Peritoneal Dialysi
Slide 49: Types of Access for Hemodialysis
4 9 TYPES OF ACCESS FOR HEMODIALYSIS 1) http://www.aakp.org/library/attachments/understandingyourhemodialysisaccessoptionseng.pdf Secondary/Graft Current Estimates of Access in the US Primary/AV Fistula (Autogenous) Venous/Temporary Catheter ~20% G r afts ~60% AV fistulas ~20% C a t he t ers
Slide 50: Vascular Access at Initiation of Dialysis
5 0 VASCULAR ACCESS AT INITIATION OF DIALYSIS 1) Hakim, Kidney International (2009) 76, 1040 – 1048 In the USA, more than 60% of patients initiate dialysis with a dialysis catheter.
Slide 51: Many Modes of AV Fistula Failure
5 1 MANY MODES OF AV FISTULA FAILURE 1) Dember et al. JAMA. 2008;299(18):2164 - 2171 Maturation – Hemodialysis Fistula Maturation Study noted that only 61% of fistulas are use - able for dialysis at 6 months 1 . Maturation failure is a large problem – Small vessels, low blood flow, inadequate vessel
Slide 52: Infection and Other Modes of Synthetic ePTFE AV Graft Failure
5 2 INFECTION AND OTHER MODES OF SYTHETIC (ePTFE) AV GRAFT FAILURE Low Durability and Poor Long - Term Patency 1 1) Based on historical, published data 2) Halbert, et al, Kidney306, 2020. • Only 70% of ePTFE grafts functional at one year • 9% annual rate of infection 2 • Vein neointimal hyperplasia,
Slide 53: Historical Success Rates for Fistulas and ePTFE Grafts
5 3 HISTORICAL SUCCESS RATES FOR FISTULAS AND ePTFE GRAFTS 1) Allon, Hemodiaysis Fistula Maturation Study, Journal of Vascular Surgery 2018; 2) Arhuidese, Journal of Vascular Surgery 2018; 3) Lok, et al, CJASN 2013; 4) Halbert, R., et al, Kidney360, 2020; 5) Kakisis, et al, Journal of Vascular Surge
Slide 54: Summary of AV Access Standards of Care
5 4 SUMMARY OF AV ACCESS STANDARDS OF CARE Standards of vascular access in the US remain the lowest in the industrialized world • Highest rate of central catheter use • Lowest successful fistula maturation and use rate: 40 - 60% of fistulas do not mature • Infection is a common cause of ePTFE graft
Slide 55: Arteriovenous Access for Hemodialysis
Arteriovenous Access for Hemodialysis TARGET INDICATION : Use of HAV as a conduit for hemodialysis, for patients who are at high risk of fistula failure or non - maturation, or at high risk of vascular access infection . Dr. Laura Niklason
Slide 56: Target Indication: HAV Will Address Fistula Failures, Infections
5 6 TARGET INDICATION: HAV WILL ADDRESS FISTULA FAILURES, INFECTIONS 1) Lawson, J.H, et al, The Lancet 2016; 387: 2026 - 2034.; 2) Halbert, R.J., et al, Kidney360 2020; doi: 10.34067/KID.003502020. Source: Humacyte AV Fistula 65% Market Share Strategy in Dialysis Access is to target the “gold standa
Slide 57: Two Phase 2 Trials in Dialysis Access: V001 and V003
5 7 TWO, PHASE 2 TRIALS IN DIALYSIS ACCESS: V001 and V003 Enrollment: 60 total subjects enrolled from December 2012 – May 2014. • 40 subjects in V001 • 20 subjects in V003 NCT01840956 and NCT01744418: Safety and Efficacy of a vascular prosthesis for hemodialysis access in patients with end - stage r
Slide 58: V001 Update: Outstanding Long-Term Durability
5 8 V001 UPDATE: OUTSTANDING LONG - TERM DURABILITY 1) Lok, et al; 2013 CJASN 2) Kakisis et al; 2017, JVS 3) Arhuidese, et al, 2018; JVS 97 94 79 58 0 . 5 1 2 5 HAV Secondary Patency (%) 59 54 30 27 1 2 5 Fistula Secondary Patency (%) ePTFE Secondary Patency (%) Time (years) Needle punctures over 6
Slide 59: First of Two Phase 3 Trials in Dialysis Access: V006 HUMANITY
5 9 FIRST OF TWO PHASE 3 TRIALS IN DIALYSIS ACCESS: V006 HUMANITY Enrollment: 355 total subjects; 1:1 prospective randomization HAV (6mm x 42cm) vs. ePTFE grafts NCT02644941: An Assessment of Humacyte’s Human Acellular Vessel in Patients Needing Renal Replacement Therapy: A Comparison with ePTFE Gra
Slide 60: Phase 3 V006 HUMANITY Trial Subject Demographics
6 0 PHASE 3 V006 HUMANITY TRIAL SUBJECT DEMOGRAPHICS 1) United States Renal data system (USRDS) report V006 Demographics (N = 355) ePTFE (n=178) HAV (n=177) Age (years) 60 63 Male (%) 49% 50% Caucasian (%) 65% 70% Black (%) 28% 25% Hispanic (%) 11% 15% Asian / Other (%) 3% 2% Body Mass Index (BMI) 2
Slide 61: Phase 3 V006 HUMANITY Trial: Secondary Patency Results
6 1 1) Secondary Patency is defined as the time between initial implantation and abandonment of the conduit PHASE 3 V006 HUMANITY TRIAL: SECONDARY PATENCY RESULTS Statistical Approach: Cox Proportional Hazards Model Cox Proportional Hazards Model for Time to Loss of Secondary Patency Treatment Group
Slide 62: Phase 3 V006 HUMANITY Trial: Secondary Patency Results (RMST)
6 2 R MS T A n a l y s i s fo r T i m e t o Lo s s o f Sec ond ar y Pa t e n cy Treatment Group (HAV vs ePTFE) Timepoint Difference Non - inferiority Margin Hazard Non - inferiority Demonstrated (Yes/No) Estimate 95% CI 12 months 16.949 ( - 1.77, 35.67) - 21.06 Yes 24 months 1.563 ( - 46.72, 49.84)
Slide 63: HAV Patency Surpassed Published ePTFE and Fistula Patencies
6 3 HAV PATENCY IN PHASE 3 V006 HUMANITY TRIAL SURPASSED PUBLISHED ePTFE and FISTULA PATENCIES 1) Halbert, et al, Kidney360; 2020; 1 (12) 1437 - 1446 2) Arhuidese, I.J., et al. Journal Vascular Surgery 2018; 68: 1166 - 1174 3) Allon, M., et al. American J Kidney Disease 2018; 71: 677 - 689. Secondar
Slide 64: Primary Safety Endpoint: HAV Had ~5x Fewer Infections Than ePTFE
6 4 PRIMARY SAFETY ENDPOINT: HAV HAD ~5x FEWER INFECTIONS THAN ePTFE IN V006 TRIAL 1) 1 de Jager DJ et al. JAMA 2009; 302: 1782 – 1789 H AV EP TFE HAV ePTFE 4 . 5% ePTFE Infections 5x of HAV p = 0.04 9 3 15 13 S U BJE C T S N EE D I N G HOSPITALIZATION ePTFE SUBJECTS NEEDING IV ANTIBIOTICS H A V Inf
Slide 65: PRA Increases Were Worse for ePTFE Than for HAV Patients
6 5 PRA INCREASES WERE WORSE FOR ePTFE THAN FOR DIALYSIS HAV PATIENTS 1) Dawson 2011 • Panel Reactive Antibodies (PRAs) measure antibodies against donor organs. cPRA values range from 0 – 100%. • Patients with cPRA > 20% are considered “sensitized” and are difficult to cross - match for transplants.
Slide 66: Mean Diameter of HAV Comparable to ePTFE
MEAN DIAMETER OF HAV WAS COMPARABLE TO ePTFE AT KEY MEASUREMENT POINTS OF THE TRIAL 6.2 6.3 6.0 5. 7 5.7 5.7 5.7 5.9 Day 7 Month 12 Month 24 Mean Inner Diameter of Conduit (mm) Month 18 HAV ePTFE 66 6.0mm nominal conduit diameter
Slide 67: Blood Flow Rate of HAV Comparable to ePTFE
BLOOD FLOW RATE OF HAV WAS COMPARABLE TO ePTFE AT KEY MEASUREMENT POINTS OF THE TRIAL 1,231 1,121 1,075 994 1,195 1,131 1,122 1,096 Day 7 Month 12 Month 24 Mean Blood Flow Rate (mL/min) Month 18 HAV ePTFE 67
Slide 68: HAV Had Fewer Removals Than ePTFE
HAV HAD FEWER REMOVALS THAN ePTFE • For HAVs, 42% had angioplasties with over - sized balloons, and these HAVs had a significant increase in interventions. • When HAVs were handled as directed, interventions were similar for HAV and ePTFE. • In V006, ePTFE grafts had to be removed from patients more
Slide 69: Secondary Patency Higher at Sites With Previous HAV Experience
SECONDARY PATENCY WAS HIGHER IN CLINICAL SITES WITH PREVIOUS HAV EXPERIENCE • Kaplan - Meier curve of HAV and ePTFE graft secondary patency at 4 sites with previous HAV experience • HAV secondary patency was 100% until 18 months at sites with prior HAV experience (from Phase 2 studies) 69
Slide 70: Factors Potentially Affecting V006 HUMANITY Trial Outcomes
FACTORS POTENTIALLY AFFECTING V006 HUMANITY TRIAL OUTCOMES MONITORING and FOLLOW - UP: • Frequent study - mandated ultrasounds (at 1, 3, 6, 12, 18 and 24 months), which exceed standard of care, provided enhanced ability of surgeons to monitor ePTFE study conduits. • Over 40% of HAVs in the HUMANITY
Slide 71: V006 HUMANITY Trial Supports Utility of HAV
V006 HUMANITY TRIAL SUPPORTS UTILITY OF HAV IN PATIENTS AT RISK FOR INFECTION OR FISTULA NON - MATURATION 71 • The HUMANITY trial showed that the HAV is safe and functional for dialysis access . • HAV in the HUMANITY trial performed as expected, and predicted, from Phase 2 data. • The performance of
Slide 72: Enrolling Phase 3 Trial in Dialysis Access Versus AV Fistula (V007)
ENROLLING PHASE 3 TRIAL IN DIALYSIS ACCESS VERSUS AV FISTULA (V007) 72 Enrollment: Target 240 total subjects (over 185 subjects enrolled through April 2021);1:1 Prospective randomization HAV (6mm x 42cm) vs. autogenous fistula NCT03183245: Compare the Efficacy and Safety of Humacyte’s Human Acellula
Slide 73: Learnings From HUMANITY Applied to V007 Trial
LEARNINGS FROM HUMANITY THAT HAVE BEEN APPLIED TO V007 TRIAL MONITORING and FOLLOW - UP: • Pro - active teaching at all clinical sites around suitable interventions for the HAV : angioplasty balloon size, etc . • Monitoring sites for inappropriate interventions and provide additional, specific instr
Slide 74: Data From Phase 2 and Phase 3 Compared to Prior Fistula Publications
7 4 DATA FROM PHASE 2 AND PHASE 3 COMPARED TO PRIOR FISTULA PUBLICATIONS HAV Phase 2 DATA HAV Phase 3 DATA Fistula, published data, not head - to - head Expected Indication: Use of HAV as a conduit for hemodialysis, for patients who are at high risk of fistula failure or non - maturation or at high
Slide 75: HAV May Reduce Infection and Catheter Contact Time
7 5 HAV MAY REDUCE INFECTION AND CATHETER CONTACT TIME. INFECTIONS AND CATHETERS ARE MORBID FOR PATIENTS, AND COSTLY TO THE SYSTEM 1) USRDS Expenditures on ESRD 2018, and 2008. • Catheters cost $23,000 more , per year, than working fistulas. • ePTFE costs $17,000 more , per year, than working fistul
Slide 76: Estimated Milestones and Value Inflection Points for AV Access Program
7 6 ESTIMATED MILESTONES AND VALUE INFLECTION POINTS F O R A V ACCES S PROGRAM Q 4 2021 Complete enrollment of V 007 trial comparing HAV vs . autogenous fistula Q1 2023 Top - line readout for V007 trial – 12 - month follow - up from last subject enrolled. Mid - 2023 File BLA for AV Access , includin
Slide 77: Fresenius Is a Global Dialysis Leader and Strong Humacyte Partner
7 7 FRESENIUS IS A GLOBAL DIALYSIS LEADER AND STRONG HUMACYTE PARTNER • Fresenius made strategic investment in Humacyte of $150M in 2018. • Fresenius participated in Alpha SPAC’s PIPE fundraise as the largest single investor • Humacyte and Fresenius collaborating on clinical trial designs in Europe
Slide 78: Peripheral Artery Disease Treatment
Jack L. Cronenwett, M.D. Professor of Surgery Dartmouth - Hitchcock Medical Center Peripheral Artery Disease Treatment
Slide 79: Peripheral Artery Disease (PAD)
Peripheral Artery Disease (PAD) JACK L. CRONENWETT, M.D. Caused by atherosclerosis • Like coronary heart disease • Most commonly affects legs (can involve any artery) A ge % US Population Prevalence of PAD in U.S. Affects 10 Million Americans > age 40 • Increases with age, > 20% by age 80 Narrowed a
Slide 80: Peripheral Artery Disease (PAD)
Peripheral Artery Disease (PAD) JACK L. CRONENWETT, M.D. Can progress to multiple leg arteries, further reducing circulation Treatment requires restoration of blood flow • Non - surgical, catheter - based intervention • Surgical bypass Critical Limb Threatening Ischemia • Tissue does not receive eno
Slide 81: Peripheral Artery Disease Treatment
Peripheral Artery Disease Treatment JACK L. CRONENWETT, M.D. Peripheral Vascular Intervention (PVI) Balloon Angioplasty or Stenting • Less invasive, percutaneous procedure • Used for less severe disease • Increasing in frequency Surgical Bypass • Used for more severe disease • Different levels based
Slide 82: Conduit Used for Leg Bypass Surgery
Conduit Used for Leg Bypass Surgery JACK L. CRONENWETT, M.D. Saphenous Vein Grafts (54%) • Best patency, lowest reintervention rate • More resistant to infection • Only suitable in ~ half of cases • Require long leg incision to harvest – Increases risk and complications – Other veins (arm) used in o
Slide 83: Leg Bypass Grafts: Current Challenges
Leg Bypass Grafts: Current Challenges JACK L. CRONENWETT, M.D. • Saphenous vein grafts often not suitable and require morbid incisions • Synthetic grafts have worse patency, higher reintervention/ amputation • Biologic grafts have worse patency and degeneration Opportunities for HAV in treatment of
Slide 84: Peripheral Arterial Disease Phase 2 Trials
Peripheral Arterial Disease Phase 2 Trials Dr. Laura Niklason
Slide 85: Phase 2 V002 Trial in Peripheral Arterial Disease
8 5 PHASE 2 V002 TRIAL IN PERIPHERAL ARTERIAL DISEASE (PAD) Enrollment: 20 total subjects, enrolled from October 2013 – June 2014 ; all patients received the HAV ( 6 mm x 42 cm) NCT01872208: Evaluation of the safety and efficacy of a vascular prosthesis as an above - the - knee graft in patients wit
Slide 86: Phase 2 V002 Trial: Demographics and Safety
8 6 PHASE 2 V002 TRIAL: DEMOGRAPHICS AND SAFETY 1: Gutowski, et al, 2020, Journal of Vascular Surgery. Demographics 1 Age average 66 yo (54 – 79 yo) Male 65% Female 35% Hypertension 75% Diabetic 45% Cardiovascular disease 25% Distal anastomosis of an HAV in V002 trial Severity of Disease Median clau
Slide 87: Phase 2 V002 Trial Update: Results Show HAV Durability
8 7 PHASE 2 V002 TRIAL UPDATE: 6 - YEAR RESULTS SHOW HAV DURABILITY 1) Vartanian and Conte, 2015; Circulation Research 2) Rychlik 2014 Journal of Vascular Surgery 3) Siracuse 2013 In PAD, 40% of patients do not have ipsilateral Saphenous Vein available 1 . Those patients are forced to use lesser vei
Slide 88: Long-Term Imaging Indicates That the HAV Is Durable
LONG - TERM IMAGING INDICATES THAT THE HAV IS DURABLE V002 - 01 - 008: 51 months V002 - 01 - 005: 51 months V002 - 01 - 008: 50 months 88 Scale bars in images show dimensions in mm. “anast” denotes “anastomosis”. “anast” denotes “anastomosis”.
Slide 89: Phase 2 V004 Trial in PAD in U.S.
PHASE 2 V004 TRIAL IN PAD IN U.S. 89 Enrollment: 15 total subjects, enrolled from December 2016 – December 2019; all patients received the HAV (6mm x 42cm) NCT02887859: A phase 2 study for the evaluation of safety and efficacy of Humacyte’s Human Acellular Vessel for use as a vascular prosthesis for
Slide 90: Phase 2 V004 Update: Data in Critical Limb Ischemia
9 0 PHASE 2 V004 UPDATE: 12 - MONTH DATA IN CRITICAL LIMB ISCHEMIA 1) Kinlay, 2016; Circulation Cardiovascular Interventions. (PREVENT III trial) 2) Benoit, et al, 2011, Journal of Translational Medicine. Results from V004 Trial (as of April 2021) Pre - Op 6 mos 12 mos Secondary Patency - 86% 64% An
Slide 91: Conclusions From Phase 2 PAD Trials With HAV
CONCLUSIONS FROM PHASE 2 PAD TRIALS WITH HAV 91 • HAV has been implanted into patients with PAD, claudication, and critical limb ischemia . • HAV is durable in the arterial system, with no reports of aneurysm out to 6 years (and counting) . • HAV has zero instances of graft infection . • HAV has zer
Slide 92: Expanded Access in PAD: HAV Urgently Requested for Multiple Patients
EXPANDED ACCESS IN PAD: THE HAV HAS BEEN URGENTLY REQUESTED FOR MULTIPLE PATIENTS 92 Date Location Injury Implant Location Last known status 8 - May - 19 Walter Reed National Military Medical Center 70 yo limb threatening critical ischemia no viable autologous vein Superficial Femoral to T i b i a l
Slide 93: Case EA-003: Avoiding Amputation and Restoring Mobility
9 3 CASE # EA - 003: AVOIDING AMPUTATION, AND RESTORING MOBILITY Source: Humacyte Knee joint Staples at incision HAV Pa t i en t ’ s own arteries, smaller caliber A ngiog r a m at 1 year • The patient was a 70 - year - old male with critical limb ischemia • No vein was available to perform a bypass,
Slide 94: Pediatric Heart Surgery
Dr. Chris Breuer Director of the Center for Regenerative Medicine Nationwide Children's Hospital Pediatric Heart Surgery
Slide 95: Congenital Heart Disease Statistics
IATIONWIDE CHILDRENS part ba gg 40,000 infants are born in the US each year with CHD 3 MILLION people living with CHD in the US today CHD is th i ;|affecting hegears 1in 100 }#@ sic birth defect | NE WbDOrNns deaths THERE IS NO CURE 3:4%|SQBILLION 2009 direct hospital costs for CHD patients <10 PERC
Slide 96: Cyanotic Congenital Heart Disease
CYANOTIC CONGENITAL HEART DISEASE DR. CHRIS BREUER 96
Slide 97: Stages of HLHS: Fontan Procedure
Ce of HLHS: Fontan Cit Stage tt ‘Amesified Fontan procedure is Completed 6-12 months ater Sage utilizing an exracardiac GOR: TEX” condo connect infer ver Nariogwie Critpreys fiw to the pulmonary artery Closed purse sing for ‘ype cannoli Systemic venous bod bypasses the ight heart deci to ‘te puimona
Slide 98: af Narionwipe CHILDRENS
af Narionwipe CHILDRENS
Slide 99: WE Narioywine Cunpreys
WE Narioywine Cunpreys
Slide 100: NATIONWIDE CHILDRENS
2 NATIONWIDE CHILDRENS
Slide 101: Humacyte Innovation in Cardiac Grafts
Humacyte Innovation in Cardiac Grafts Dr. Laura Niklason
Slide 102: Pediatric Heart Defects
102 PEDIATRIC HEART DEFECTS 1) Parry et al., 2000; 2) Wells et al., 2005; 3)Williams et al., Annals of Thoracic Surgery 2007 • Congenital Heart Defects (CHDs) occur in 1% of babies (40,000) born each year in U.S. • Blalock - Taussig (BT) Shunt – Palliative systemic - to - pulmonary conduit, typicall
Slide 103: Small Diameter HAV in Pediatric Heart Surgery
SMALL DIAMETER HAV IN PEDIATRIC HEART SURGERY Tremendous opportunity to help pediatric patients in numerous applications with BT Shunt identified as a first step The Small Diameter, 3.5mm HAV is currently being investigated as a BT Shunt in a preclinical juvenile primate model using angiography, MRI
Slide 104: Small Diameter Preclinical HAV Imaging
SMALL DIAMETER PRECLINICAL HAV IMAGING Systemic C i r c u lati o n P u l m on a r y C i r c u lati o n HAV BT Shunt I mp l a nt 6 Months 3D Rotational Angiogram ( 6 Months Post - Implant) 4D Flow MRI ( 1 Month Post - Implant) HAV BT Shunt Systemic C i rc ul at io n P u lm ona ry C i rc ul at io n Sy
Slide 105: Small Diameter HAV Remodels in Preclinical Studies
SMALL DIAMETER HAV REMODELS IN PRECLINICAL STUDIES 3.5mm HAV BT Shunts in primates harvested after 6 months undergo host cellular remodeling HAV Lume n Adventitia αSMA DAPI Green Stains smooth muscle cells Blue Stains all cells HAV Lume n Adventitia HAV 105 Lume n Adventitia
Slide 106: Summary and Next Steps
SUMMARY AND NEXT STEPS 5 primates have been evaluated with our 3.5mm small diameter HAV implanted as a BT Shunt and followed for 4 - 6 months • Surgeons determined size, handling, ability to suture, and durability of the HAV was appropriate for pediatric cardiac surgery. • Juvenile primate model was
Slide 107: Video of Coronary Artery Bypass in Adult Baboon
VIDEO OF CORONARY ARTERY BYPASS IN ADULT BABOON HAV is being tested as a coronary artery bypass graft (CABG) in adult, non - human primates. This video shows a 3.5mm HAV supporting blood flow to the coronary artery of an adult baboon. If successful, data will be utilized for Pre - IND meeting reques
Slide 108: Type 1 Diabetes
Type 1 Diabetes Dr. Laura Niklason
Slide 109: Type 1 Diabetes Is a Growing Health Problem
109 TYPE 1 DIABETES IS A GROWING HEALTH PROBLEM • Like many other auto - immune diseases, Type 1 diabetes is growing at a rate of 2% in the Western world – cause of this is unknown 1 . • Insulin injections, insulin pumps, finger sticks: $10k/year 2 • Constant vigilance for blood sugar control impair
Slide 110: A Curative Therapy for Type 1 Diabetes Has Not Yet Arrived
1 1 0 A CURATIVE THERAPY FOR TYPE 1 DIABETES HAS NOT YET ARRIVED 1) https://health.costhelper.com/pancreas - transplant - cost.htm l 2) https://www.kidmey.org/atoz/content/kidpantx 3) CITR 9 th Annual Report, 2016, Collaborative Islet Transplant Registery Pancreas t r ansp l anta t i on is dangerous
Slide 111: BioVascular Pancreas May Deliver Curative Islets to Diabetics
BIOVASCULAR PANCREAS MAY DELIVER CURATIVE ISLETS TO DIABETICS • Islets die after implantation under the skin, or after injection into the abdomen, due to lack of oxygen and nutrients. • Without a blood supply, pancreatic islets cannot survive transplantation. • Humacyte’s HAV is being developed as a
Slide 112: BioVascular Pancreas Normalizes Glucose in Diabetic Animals
BIOVASCULAR PANCREAS NORMALIZES GLUCOSE IN DIABETIC ANIMALS 0 50 T i m e ( D ay) 100 0 50 100 Percent Euglycemic (%) B VP N o F l ow • Diabetic rodents implanted with BVPs containing rat islets, then followed for blood glucose levels. • All treated animals normalized glucose over time. All sham - tr
Slide 113: Bio-Engineered Lungs: Design Criteria
1 1 3 BIO - ENGINEERED LUNGS: DESIGN CRITERIA Sou r c e : H u m a c y t e • Native lungs can be decellularized, leaving behind a lung scaffold that contains airsacs and microvessels. • Lung engineering requires structural scaffolding, and a detailed understanding of cellular makeup and function of t
Slide 114: Severe Lung Disease Destroys Lung Architecture
SEVERE LUNG DISEASE DESTROYS LUNG ARCHITECTURE. A NEW LUNG SCAFFOLD, WITH NEW CELLS, IS REQUIRED TO REPLACE LUNG FUNCTION Nor m al lung Emphysematous lung Nor m al alveoli 114 Alveoli dest ro y ed
Slide 115: Long Term Goal: Create Functional Lungs
LONG TERM GOAL: CREATE FUNCTIONAL LUNGS THAT CAN CURE PATIENTS WITH END - STAGE LUNG DISEASE Bioengineered porcine lungs in bioreactors, breathing Engineered rodent lung, transplanted and breathing Lung scaffold, re - populated with lung cells in a bioreactor: 115
Slide 116: Business Update
CHuMACYTE Business Update Dale Sander
Slide 117: Merger Transaction Summary
1 1 7 MERGER TRANSACTION SUMMARY T r a n sac tion Structure • Existing Humacyte shareholders to receive the following consideration in AHAC common shares: – Base valuation of $800 million – Plus, stock performance linked incentive when the share price reaches or exceeds the following levels, for at
Slide 118: Projected Merger and Financing Timeline
1 1 8 PROJECTED MERGER AND FINANCING TIMELINE Date Milestone COMPLETED MILESTONES February 17, 2021 Announcement of Intent to Merge March 3, 2021 Hart Scott Rodino (HSR) antitrust filing March 22, 2021 Alpha/Humacyte file S - 4 / Proxy with SEC April 7, 2021 Completion of $50 million debt facility w
Slide 119: Anticipated Use of Proceeds
1 1 9 ANTICIPATED USE OF PROCEEDS Source: Humacyte BLA submissions in Dialysis AV Access and Vascular Repair • Completion of Phase III trials • BLA Submissions and FDA approval Commercial launch of HAV • U.S. market launches in dialysis AV access and vascular repair • Subsequent market launches in k
Slide 120: Upcoming Milestones for Humacyte
120 UPCOMING MILESTONES FOR HUMACYTE Q3 - Q4 2021 Complete agreement with FDA (V005 Trauma: number of subjects and comparator) 2022 Completion of V005 Trauma trial enrollment, early trial results, depends on FDA - agreed trial size Late - 2022 File BLA for Vascular Trauma. A nt ici pat e A cc e l er
Slide 121: Humacyte Incorporated Contact Information
Humacyte Incorporated Contact Information: • Dr. Laura Niklason, CEO & Founder, niklason@humacyte.com • Dale Sander, CFO, dsander@humacyte.com Off i ce A dd ress: 2525 E. Highway NC 54 Durham, NC 27713
Slide 122: V006 HUMANITY Trial Comparison
comparison ePTFE HAV months 6 12 18 24 6 12 18 24 Secondary Patency (V006 Trial) 87% (81 - 92%) 80% (73 - 85%) 77% (70 - 83%) 74% (67 - 81%) 92% (87 - 95%) 82% (75 - 87%) 73% (65 - 79%) 67% (59 - 74%) Non - inferiority, secondary patency: • Cox Proportional Hazard Model (Pre - specified study endpoi
Alpha Healthcare Acquisition — SPAC Merger (June 2021) on 6ix