Xvivo Perfusion AB · OMXSTO:XVIVO
Xvivo Perfusion AB — Investor Day (September 2021)
169 slides from Xvivo Perfusion AB's investor day presentation, Sep 23, 2021
Slide 1: XVIVO Capital Markets Day
XVIVO Capital Markets Day September 23, 2021
Slide 2: Disclaimer
Disclaimer Forward-looking statement The information contained in this presentation by XVIVO Perfusion results and developments to differ materially from those expressed The information presented at the Capital Markets Day is intended AB (publ) (the “Company”) (the ”Information”) has been prepared o
Slide 3: Agenda
Agenda 13.00 - 13.05 Introduction Lars Frick, Moderator and Dag Andersson, CEO 13.05 - 13.20 Market & trends Dag Andersson, CEO 13.20 - 13.35 Strategy Dag Andersson, CEO and Kristoffer Nordström, CFO 13.35 - 13.50 Health economics Johan Holmström, CCO 13.50 14.05 Q&A 14.05 - 14.20 Break 14.20 - 14.5
Slide 4: The need
The need With only 160,000 organ transplants Approximately, performed globally 1.6 million each year, this only organ transplants covers are required every year. 10% of the total need. 4
Slide 5: Waiting lists: the trend
Waiting lists The trend (a US example) It is estimated that approximately 140,000 120,000 150,000 patients 100,000 80,000 60,000 in the United States are currently w aiting for a new organ. 40,000 Approximately 25% of patients 20,000 waiting for new lungs or heart die 0 while waiting for a new organ
Slide 6: Beatrice Halby, Lung recipient
Beatrice Halby, Lung recipient 6
Slide 7: Nobody should die waiting for a new organ
We believe in an extended life of organs Nobody should die waiting for a new organ 7
Slide 8: Key facts
Key facts XVIVO is the first Experts in advanced World leading in global ‘all organ’ solutions and machines lung and liver company for transplantation transplantation Founded in HQ in Gothenburg Midcap NASDAQ 1998 Sweden Listed 2016 Employees Sales in more than 100 70 countries 8
Slide 9: Transplants per organ
Transplants per organ Lung & Heart Addressing Kidney ~98% of the market 64% Lung XVIVO’s addressable Heart market in thoracic 4% organs. 6% of global market (~6,700) 10% of global market (~8,300) Liver 24% 2% Pancreas Small bowel 0% 9
Slide 10: Our technology saves organs, so others can save lives
Our technology saves organs, so others can save lives 10
Slide 11: Our offer: We enable safe use of more organs
Our offer: We enable safe use of more organs We increase the We improve We improve organ availability of organs organ preservation function and survival 11
Slide 12: Market & trends
Market & trends Dag Andersson, CEO
Slide 13: Organ utilization rates
Organ utilization rates Utilization rate 2019 global averages Lung 20% Heart 30% Kidney 67% Liver 65% 13
Slide 14: Organ utilization must increase
Organ utilization must increase The hurdles Low utilization of Low or no use of Deterioration of donated organs DCD2 donors in organs after from DBD1 donors thoracic retrieval until transplantation transplantation 1 DBD - Donated after brain death 2 DCD - Donated after circulatory death 14
Slide 15: Deceased donor growth forecast – All organs
Deceased donor growth forecast – All organs Forecasted deceased donor growth 90000 77,000 80000 70000 60000 50000 39,000 40000 30000 20000 10000 0 2015 2016 2017 2018 2019 2020E 2021F 2022F 2023F 2024F 2025F 2026F 2027F 2028F 2029F 2030F Total DBD Donors Total DCD Donors DCD CAGR 2020 - 2030 DBD CAG
Slide 16: XVIVO is leading the transformation
XVIVO is leading the transformation MACHINE PERFUSION PLATFORMS DISPOSABLES FOR MACHINE PERFUSION STATIC PRESERVATION Lung XPS™ XPS DISPOSABLE LUNG KIT™ STEEN SOLUTION™ PERFADEX PLUS® UNDER EVALUATION IN CLINCAL TRIALS Heart Kidney Liver XVIVO HEART XVIVO DISPOSABLE KIDNEY ASSIST KIDNEY LIVER DONOR
Slide 17: Key take-aways: Market & trends
Key take-aways: Market & trends • A global organ shortage (demand 10x supply) • Organ utilization must increase • Machine perfusion will drive increased organ utilization • XVIVO has the widest machine perfusion offering in the world 17
Slide 18: Strategy
Strategy Dag Andersson, CEO and Kristoffer Nordström, CFO
Slide 19: EXTENDING HORIZONS in transplantation
What are we EXTENDING passionate about? HORIZONS in transplantation What drives our Revenue/ What shall we be Machine ECONOMIC Installed the best in the perfusion ENGINE? machine world at? 19
Slide 20: Strategy overview 2022-2026
Strategy overview 2022-2026 We believe in an extended life for organs. Our purpose Nobody should die waiting for a new organ. Our strategic Global leading ‘all organ’ company objective Our economic Global leader in machine perfusion – Revenue/Installed machine engine Global leader Market leading Inc
Slide 21: Strategic focus areas
Strategic focus areas xVIVO
Slide 22: Our strategic focus areas 2022-2026
Our strategic focus areas 2022-2026 Global leader Market leading Increase Secure all-inclusive China to become Abdominal (the US) heart preservation penetration of reimbursement in our second largest system machine perfusion key geographies market Qualifier Key activities • FDA clearance for Kidney
Slide 23: Our strategic focus areas 2022-2026
Our strategic focus areas 2022-2026 Global leader Market leading Increase Secure all-inclusive China to become Abdominal (the US) heart preservation penetration of reimbursement in our second largest system machine perfusion key geographies market Qualifier Key activities • Clinical trials in Europe
Slide 24: Our strategic focus areas 2022-2026
Our strategic focus areas 2022-2026 Global leader Market leading Increase Secure all-inclusive China to become Abdominal (the US) heart preservation penetration of reimbursement in our second largest system machine perfusion key geographies market Qualifier Key activities • Forward integration and n
Slide 25: Our strategic focus areas 2022-2026
Our strategic focus areas 2022-2026 Global leader Market leading Increase Secure all-inclusive China to become Abdominal (the US) heart preservation penetration of reimbursement in our second largest system machine perfusion key geographies market Qualifier Key activities • Drive and support reimbur
Slide 26: Our strategic focus areas 2022-2026
Our strategic focus areas 2022-2026 Global leader Market leading Increase Secure all-inclusive China to become Abdominal (the US) heart preservation penetration of reimbursement in our second largest system machine perfusion key geographies market Qualifier Key activities • Regulatory strategy to ga
Slide 27: Financial targets
Financial targets Kristoffer Nordström, CFO
Slide 28: World leading – 20 years of experience
The beginning of a journey World leading – 20 years of experience 28
Slide 29: Our business model
Our business model Economic engine KPI Revenue model Revenue/ Razor / Machine Installed Razor perfusion machine blades 29
Slide 30: Strong double-digit growth
Strong double-digit growth MSEK Pandemic impact on 220 sales and product mix CAGR*: 21.3% 188 180 Lung sales 148 138 • Static preservation 120 118 has historically 85 grown with the 69 market 57 • Machine perfusion has shown a CAGR of 42 % until 2019 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021
Slide 31: Market value - Machine perfusion
Market value - Machine perfusion Total market value potential of machine perfusion* Market potential value split (USD) 15% Actual market 30% 20% Lung, 20% 1.3 bn Kidney, 20% Heart, 30% 20% Liver, 30% 30% *Deceased donors. Solutions and disposables only (no machines or static preservation) 31
Slide 32: 2026 – Main assumptions: Sales
2026 – Main assumptions: Sales Sales by business area Sales by region 15% 30% EMEA Abdominal 50% 50% Americas Thoracic APAC 55% 32
Slide 33: 2026 – Profitability targets
2026 – Profitability targets EBIT (%) EBITDA (%) 20 30 33
Slide 34: Key take-aways: Strategy
Key take-aways: Strategy • Five strategic focus areas will make XVIVO become the global leading ‘all organ’ company • Machine perfusion is what we are best in the world at and our economic engine • Revenue model for lung will be applied also on kidney, liver and heart • 2026 profitability targets of
Slide 35: Health economics
Health economics Johan Holmström, CCO
Slide 36: Health benefit, the true potential of organ transplantation
Health benefit, the true potential of organ transplantation • The waiting list situation fails to 1,000,000 capture the true magnitude of the organ shortage 800,000 728,700 • The possibility to replace organs and 600,000 tissues on demand could generate health benefits on level with curing 400,000 c
Slide 37: Health benefits to drive reimbursement
Health benefits to drive reimbursement • Clinical evidence and national guidelines as a foundation • Publications, (e.g. the recent NEJM publication on HMPO2) • Perform clinical investigations on national level • Confirm and recommend clinical guidelines, e.g. NICE • Clinical guidelines to support f
Slide 38: Overview – Reimbursement
Overview – Reimbursement XVIVO is directly or indirectly involved in several initiatives that will open up reimbursement in EU countries for machine perfusion • The US covered through medicare / aid and private insurance • Asia & China: No nationwide reimbursement for specific procedures or use of c
Slide 39: NICE gives support for EVLP (the UK)
NICE gives support for EVLP (the UK) In May, XVIVO announced that The National Institute for Health and Care Excellence (NICE), had issued interventional procedure guidance recommending the use of Ex Vivo Lung Perfusion (EVLP) for preservation of lungs 2021 Next steps • Guidelines published • XVIVO
Slide 40: France - Successful case
France - Successful case Both EVLP (lung) and machine perfusion for kidney is granted reimbursement • Significant increase in available organs and improved transplant outcomes • Health care cost savings compared to number of renal services Reimbursement for machine perfusion of liver – on its way •
Slide 41: Netherlands – Positive news!
Netherlands – Positive news! Kidney machine perfusion reimbursed successfully NEWS! EVLP will be granted from January 2022 NEWS! Liver machine perfusion from January 2022 41
Slide 42: Key take-aways: Health economics
Key take-aways: Health economics • Clear health economic benefit from transplantation • XVIVO is supporting several research initiatives and projects to drive reimbursement and funding • Clinical evidence is a key driver • Debate is no longer focusing on the clinical benefits of machine perfusion bu
Slide 43: Q&A
Q&A
Slide 44: Break
Break
Slide 45: Agenda
Agenda 13.00 - 13.05 Introduction Lars Frick, Moderator and Dag Andersson, CEO 13.05 - 13.20 Market & trends Dag Andersson, CEO 13.20 - 13.35 Strategy Dag Andersson, CEO and Kristoffer Nordström, CFO 13.35 - 13.50 Health economics Johan Holmström, CCO 13.50 14.05 Q&A 14.05 - 14.20 Break 14.20 - 14.5
Slide 46: Heart
Heart Andreas Wallinder M.D., Ph.D., CMO
Slide 47: Overview: Heart
Overview: Heart The market XVIVO today Where Heart supports our strategy Key facts Market Strategic focus presence areas 2022 – 2026 No of transplants* Organ utilization rate XVIVO products • Market leading heart • 8,600 • 30% • XVIVO heart preservation system preservation system (in clinical trials
Slide 48: Heart failure
Heart failure • Heart failure is a chronic illness with a median survival of 2 years after diagnosis • Once heart failure progresses to the final stage, patients experience poor quality of life, high symptom burden and face a median life expectancy of only 6–12 months • Heart disease is the leading
Slide 49: Heart transplantation today
Heart transplantation today Adult and pediatric heart transplants Number of transplants by year and location Other Khush KK et al. J Heart Lung Transplant. 2020 Jan;39(1):91]. J Heart Lung Transplant. 2019;38(10):1056-1066. doi:10.1016/j.healun.2019.08.004 49
Slide 50: Donor heart standard of care
Donor heart standard of care The donor heart it is flushed with a cold solution that arrests the activity before explant During the first 50 years of heart transplant donor hearts have been placed in plastic bags with cold solution and placed on ice in a cooler during transport Once the heart is arr
Slide 51: Impact of ischemic time
Impact of ischemic time 2.5 2.5 Hazard Ratio of 1 Year Mortality 2.0 2.0 1.5 1.5 1.0 1.0 0.5 0.5 0.0 0.0 1 2 3 4 5 6 15 20 25 30 35 40 45 50 55 60 Ischemic time (hours) Donor age (years) Khush KK et al. J Heart Lung Transplant. 2020 Jan;39(1):91]. J Heart Lung Transplant. 2019;38(10):1056-1066. doi:
Slide 52: 2h 3h 6h
2h 3h 6h 52
Slide 53: Early causes of death after heart transplantation
Early causes of death after heart transplantation • Failure of the transplanted heart is the leading cause of death after transplantation • Injury to the donor heart during transport on ice is causing poor function in the recipient JHLT. 2019 Oct; 38(10): 1015-1066 53
Slide 54: Challenges in donor heart preservation
Challenges in donor heart preservation Ischemic injury to the donor heart There is need for a better during transport on ice is causing poor function after transplantation preservation method for in the recipient. donor hearts • Surgical teams turn down more than 70% of donor hearts today The transp
Slide 55: The evolution of non-ischemic heart preservation (NIHP)
The evolution of non-ischemic heart preservation (NIHP) From cold static storage on ice To Continuous oxygenated perfusion with a tailored solution 55
Slide 56: Preclinical proof of concept studies demonstrates
Preclinical proof of concept studies demonstrates • Reduced ischemic injury > Better organ quality after transplant • Longer preservation time possible (24 hours) • Allowed long term survival in Pig to Primate transplant (Xeno) 56
Slide 57: Non-ischemic heart preservation (NIHP)
Non-ischemic heart preservation (NIHP) 57
Slide 58: XVIVO Heart System
XVIVO Heart System Creates an optimal environment by supplying the resting heart with important substances in an oxygenated solution. Device Solution Disposable A portable Buffered and A single-use device used to supplemented set to be preserve solution for installed and hearts using flushing of the
Slide 59: First in human study
First in human study • Sponsor: Skåne University Hospital, Lund • Initial results published 2020 • Interim results presented at the European Society of Organ Transplantation (ESOT) Meeting Milan September 2021 • 100% 6-month survival without graft failure • Recruitment ongoing 59
Slide 60: NIHP Australia / New Zealand
NIHP Australia / New Zealand • Sponsor: Alfred Health, Melbourne, Australia • Explore extended transport times of donor hearts with NIHP (6-8 hours) • First hearts with extended ischemic times successfully transplanted 60
Slide 61: XVIVO sponsored studies
XVIVO sponsored studies (NIHP EU) (NIHP US) • First patient reported • Ongoing discussion with December 2020 FDA in preparation for IDE submission • Recruiting at 6 sites • Additional preclinical test • Standard donor hearts and ongoing in September and transport times less than October 6 hours • ID
Slide 62: Key take-aways: Heart
Key take-aways: Heart XVIVO’s game changing heart preservation technology has potential to: • Improve outcome after heart transplantation by replacing the cold, ischemic storage on ice used today with oxygenated perfusion of the donor heart with an optimal solution • Safely extend the time a donor h
Slide 63: The European NIHP study
The European NIHP study -Non-ischemic heart preservation Prof. Filip Rega, The University Hospitals Leuven
Slide 64: Non-Ischemic Heart Preservation
Non-Ischemic Heart Preservation Capital Markets Day November 23, 2021 Filip Rega, MD, PhD Head of Clinic, University Hospitals Leuven, Belgium Professor, Cardiovascular Sciences, KU Leuven, Belgium Director of the Leuven Surgical Heart Transplant Program Principal Investigator NIHP Trial
Slide 65: Leuven – NIHP
THE LANCET Transplantation of lungs from a non-heart-beating donor Long-term Preservation With Interim Evaluation of Lungs From a Non-Heart-Beating Donor After a Warm Ischemic Interval of 90 Minutes Filip R. Rega, MD,* Nicole C. Jannis,* Geert M. Verleden, MD, PhD,¥ Toni E. Lerut, MD, PhD,{ and Dirk
Slide 66: Leuven – NIHP
Leuven – NIHP Number of centers Percentage of transplants 140 70 120 60 Number of centers 100 50 % of transplants 80 123 40 60 30 40 20 66 59 57 20 6 10 22 8 4 0 0 1-4 5-9 10-19 20-29 30-39 40-49 50-74 75+ Average number of heart transplants per year 66
Slide 67: Leuven – NIHP
ORIGINAL ARTICLE Transplantation of donor hearts after circulatory death using normothermic regional perfusion and cold storage preservation Katrien Vandendriessche @ *"*, Vincent Tchana-Sato @ ‘, Didier Ledoux @ *, Karlien Degezelle’, ‘Stetfen Rex @ ™*, Arne Neyrinck @ »*, na Jochmans @ “6, Diethar
Slide 68: NIHP
NIHP • SCS is the standard method for organ preservation • Limitations SCS • Prolonged preservation leads to tissue damage 3 Relative Risk of 1 Year Mortality 2.5 2 1.5 1 0.5 p = 0.020 0 30 60 90 120 150 180 210 240 270 300 330 360 Ischemia Time (minutes) 68
Slide 69: NIHP
NIHP • SCS is the standard method for organ preservation • Limitations SCS • Prolonged preservation leads to tissue damage 3 Relative Risk of 1 Year Mortality 2.5 2 1.5 1 0.5 p = 0.020 0 30 60 90 120 150 180 210 240 270 300 330 360 ISHLT 2007 Ischemia Time (minutes) ISHLT 2018 69
Slide 70: NIHP
NIHP • SCS is the standard method for organ preservation • Limitations SCS • Prolonged preservation leads to tissue damage • Difficulty to assess donor function • Limited opportunity for organ repair • Need to extend preservation times 70
Slide 71: NIHP
71 NIHP eee © Wha stae ‘ORIGINAL ARTICLE Intact endothelial and contractile function of coronary artery after 8 hours of heart preservation ‘Guangqi Qin, Trygve Sjoberg, Qiuming Liao, Kiaoke Sun and Stig Steen Oxpaament of ic Suge Lind Ube and She Urverty Hox Lund esr auc esrory (bjt. The am of the
Slide 72: NIHP
NIHP OK COMMUNICATIONS ARTICLE Sree renee OPEN A nonrandomized open-label phase 2 trial of nonischemic heart preservation for human heart transplantation Johan Nilsson@ '*, Victoria Jernryd', Guangqi Qin@ ', Audrius Paskevicius', Carsten Metzsch’, Trygve Sjéberg' & Stig Steen! UZ LEUVEN J 72
Slide 73: NIHP – EU Trial
23 NIHP — EU Trial [ID us. National Library of Medicine Find Studies ~ About Studies + Submit Studies ¥ Resources ¥ About Site» PRS Login ClinicalTrials.gov Home > Search Results > Study Record Detail Save this study Non-ischemic Preservation of the Donor Heart in Heart Transplantation Clinica'Trial
Slide 74: Leuven – NIHP
Leuven – NIHP Milestones overview • June 6, 2019 - XVIVO NIHP File received by the UZL Clinical Trial Center • January 2020 – Training nursing, perfusion, residents & staff • March 24, 2020 – Approval by the Ethical Committee • April 2020 – Site initiation visit, CRF, … • June 17, 2020 – Contract XV
Slide 75: Leuven – NIHP
Leuven – NIHP Milestones overview • November 25, 2020 – Patient 1001 HTx 75
Slide 76: Leuven – NIHP
Leuven – NIHP Milestones overview • November 25, 2020 – Patient 1001 HTx 76
Slide 77: Leuven – NIHP
Leuven – NIHP Milestones overview • Since June 15th, 14 patients randomized • 6 Randomized to NIHP, All transplanted • 7 Randomized to Control • 1 Donor VSD closure – recipient succesfully transplanted • 3 Re-Htx, 3 DCD, 1 Cong • 1 patient transplanted while considering IC 77
Slide 78: NIHP – EU Trial
NIHP – EU Trial • Coordinating Principal Investigator Prof Rega, Leuven • Randomized trial (202 pt) Ice vs. NIHP • 6 active sites Leuven, Paris, Gothenburg, Madrid, Berlin, Munich. • Additional site under preparation • First patient reported Dec 2020 • Currently about 40 patient included 78
Slide 79: Potential Benefits – Short term
Potential Benefits – Short term Xvivo Heart was again terrific – even with severe PH in recipient no real problems (also thanks to top anesthesia off course) 79
Slide 80: Potential Benefits – Long term
Potential Benefits – Long term • Graft outcome • Logistics • Organ recovery marginal donors • DPP in DCD heart transplantation 80
Slide 81: Potential Benefits – Long term
Potential Benefits – Long term • Graft outcome • Outcome after heart tx • LVAD so far no major advancement • Logistics • Paper 24 hrs • Organ recovery marginal donors • DPP in DCD heart transplantation 81
Slide 82: Potential Benefits – Long term
Potential Benefits – Long term • Graft outcome • Logistics • Organ recovery marginal donors • DPP in DCD heart transplantation 82
Slide 83: Potential Benefits – Long term
Potential Benefits – Long term • Graft outcome • Logistics • Organ recovery marginal donors • DPP in DCD heart transplantation 83
Slide 84: Non-Ischemic Heart Preservation
Non-Ischemic Heart Preservation Capital Markets Day November 23, 2021 Filip Rega, MD, PhD Head of Clinic, University Hospitals Leuven, Belgium Professor, Cardiovascular Sciences, KU Leuven, Belgium Director of the Leuven Surgical Heart Transplant Program Principal Investigator NIHP Trial
Slide 85: Abdominal
Abdominal Arjan v.d. Plaats, R&D Director and Johan Holmström, CCO
Slide 86: Overview: Abdominal
Overview: Abdominal The market XVIVO today Where Abdominal supports our strategy Key facts Market Strategic focus presence areas 2022 – 2026 No of transplants* Organ utilization rate XVIVO products • Global leader Abdominal (the US) • Kidney 62,000** • Kidney 67% • Liver Assist • Increase penetratio
Slide 87: Abdominal product line
Abdominal product line Arjan v.d. Plaats, R&D Director
Slide 88: XVIVO – Abdominal portfolio
XVIVO – Abdominal portfolio Kidney Assist Liver Transport Assist XVIVO’s portable XVIVO’s platform for system for cold, cold and warm oxygenated perfusion oxygenated perfusion of donor kidneys of donor livers 88
Slide 89: XVIVO’s Kidney Assist Transport
XVIVO’s Kidney Assist Transport • XVIVO’s Kidney Assist Transport provides improved preservation of donor kidneys leading to better transplantation outcomes • Cold machine perfusion leads to improved graft survival and reduced delayed graft function after transplantation compared to static cold stor
Slide 90: Results from the COMPARE trial
1 Results from the COMPARE trial 75 Standard-HMP Filtration rate (mL/min/1,73m2 ) Improved renal function by • United Kingdom (Ploeg, Oxford) 47.6 11.7% 50 42.6 • The Netherlands (Hofker, Groningen) 25 • Belgium (Jochmans, Leuven) 0 P=0.035 st andard HM P HMP + O2 • Double blinded 18 Graft loss afte
Slide 91: XVIVO’s Liver Assist
XVIVO’s Liver Assist • XVIVO’s Liver Assist provides improved preservation of donor livers leading to better transplantation outcomes • Cold OXYGENATED machine perfusion leads to: • Reduced ischemia-reperfusion injury (DCD)1 • Lower biliary complications (DCD)1,2 • Less early allograft injury (ECD)3
Slide 92: Results from the dHOPE trial
Results from the dHOPE trial1 25 Static cold storage Non-anastomotic strictures (%) • The Netherlands (Porte, Groningen) 20 18 67% • Belgium (Monbaliu, Leuven) 15 • United Kingdom (Heaton, London) 10 Lower incidence of 6 5 biliary strictures • Computer- randomized study • 156 livers included in tota
Slide 93: XVIVO’s Liver Assist
XVIVO’s Liver Assist • XVIVO’s Liver Assist provides normothermic evaluation of previously-declined donor livers leading to more livers to become available for transplantation • 20% increase in liver transplantation combining hypothermic and normothermic machine perfusion1 • Safe use of initially re
Slide 94: Dedicated protocols for optimal use of donor livers
Dedicated protocols for optimal use of donor livers Regular Regular Split livers and High-risk (ECD**) DBD livers DCD livers logistic reasons (DBD/DCD) livers Static cold storage Static cold storage Static cold storage Static cold storage ∽40% ∽40% < 5% ∽20% dHOPE dHOPE dHOPE + NMP Viability assessm
Slide 95: Key take-aways: Abdominal (product line)
Key take-aways: Abdominal (product line) • Cold oxygenated machine perfusion improves success rate of kidney and liver transplantation (incl. DCD organs) • Clinical data, from successful machine perfusion studies, has been published for kidney and liver perfusion in The Lancet and New England Journa
Slide 96: Abdominal – US go to market
Abdominal – US go to market Johan Holmström, CCO
Slide 97: The transplant market today
The transplant market today* Liver Kidney No of Tx 28,000 62,000 Americas 30% 34% Europe 32% 32% RoW 38% 34% Active clinics 1,000 2,200 *Solid organs from deceased donors, 2019 figures 97
Slide 98: US market development - Kidney and Liver
US market development - Kidney and Liver Market opportunity DCD CAGR DBD CAGR • US transplants expected to (2019-2026) (2019-2026) increase to 50,000 by 2026 • Transplant volume development Kidney 14.3% 3.2% driven by disproportional growth of DCD • XVIVO machine perfusion Liver 17.3% 2.4% technolog
Slide 99: AOPO 50k transplants by 2026 campaign
AOPO 50k transplants by 2026 campaign The Association of Organ Procurement Organizations (AOPO) commits to achieving 50,000 annual transplants by 2026. AOPO and its members will work with key stakeholders to implement a series of initiatives: 1. Expand Collaboration 2. Reduce Health Inequities 3. Ma
Slide 100: Launch focus – Kidney Assist Transport
Launch focus – Kidney Assist Transport • Our first product launch in the US will be Kidney Assist Transport • The Kidney Assist Transport is XVIVO’s transportable organ preservation system designed for kidneys • In May 2021, XVIVO announced its submission of a 510(k) file with US FDA for Kidney Assi
Slide 101: Go to market model and value proposition
Go to market model and value proposition • Positioned as a premium product – based on a clinical and a performance proposition • Our clinical proposition with quantified clinical advantages – driving improved transplantation outcomes • Kidney Assist Transport will accommodate customers need to impro
Slide 102: Target launch dates – the US
Target launch dates – the US Kidney Assist Liver Transport Assist • Target launch in the • Process for FDA US, in January 2022 application has • Selective pre-launch started in Q4 2021 102
Slide 103: Key take-aways: Abdominal (US go to market)
Key take-aways: Abdominal (US go to market) • There is a clear ambition to significantly increase the number of transplants in the US (50k transplants in 2026) • DCD organs will drive the increase in number of organs donated • XVIVO’s ground breaking Kidney Assist Transport device to be launched lat
Slide 104: Q&A
Q&A
Slide 105: Break
Break
Slide 106: Agenda
Agenda 13.00 - 13.05 Introduction Lars Frick, Moderator and Dag Andersson, CEO 13.05 - 13.20 Market & trends Dag Andersson, CEO 13.20 - 13.35 Strategy Dag Andersson, CEO and Kristoffer Nordström, CFO 13.35 - 13.50 Health economics Johan Holmström, CCO 13.50 14.05 Q&A 14.05 - 14.20 Break 14.20 - 14.5
Slide 107: Lung
Lung Rodney Jones, Sales Director North America
Slide 108: Overview: Lung
Overview: Lung The market XVIVO today Where Lung supports our strategy Key facts Market Strategic focus presence areas 2022 – 2026 No of transplants* Organ utilization rate XVIVO products • Increase penetration of • 6,700 • 20% ® • PERFADEX Plus machine perfusion • XPSTM and STEEN SolutionTM • Secur
Slide 109: Trends and innovation – the US
Trends and innovation – the US Rodney Jones, Sales Director North America
Slide 110: Doubling the number of available lungs
Doubling the number of available lungs Cold preservation enables use of approx. 20% of all donated Today only DBD lungs. standard DBD lungs. PROCUREMENT COLD PRESERVATION TRANSPLANTATION 110
Slide 111: Doubling the number of available lungs
Doubling the number of available lungs Cold + Warm preservation enables use of approx. Today only DBD lungs. Potential Both DBD and DCD lungs. 40% of all donated standard DBD and DCD lungs. EVALUATION OF LUNG PROCUREMENT COLD PRESERVATION TRANSPLANTATION THROUGH EVLP 111
Slide 112: XPS™ with STEEN Solution™
Our EVLP Platform XPS™ with STEEN Solution™ A fully integrated platform for normothermic EVLP 112
Slide 113: EVLP
EVLP Expanding the available donor pool The ultimate objective of EVLP is to expand the available donor pool and minimize mortality and morbidity on the transplant waiting list. 113
Slide 114: Trends in lung transplants
Trends in lung transplants Lung transplants DCD lung transplants 3,000 250 2,500 200 2,000 150 1,500 100 1,000 50 500 0 0 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 OPTN data through December 31st, 2020 114
Slide 115: Exploring novel technique for expanding donor pool
Exploring NOVEL technique for expanding donor pool 5 Transplants 2.5 WIT Zero PGD3 72hrs 30 day mortality zero 80% 1 yr survival 115
Slide 116: EVLP publications over time
EVLP publications over time Publication count 80 2000 2008 2010 2014 RECENT First human Toronto group develops Launch of the first LS Launch of the XPS One publication 60 LTx after EVLP. their EVLP protocol. EVLP platform. EVLP platform. per week. 40 20 1972 1976 1980 1984 1988 1992 1996 2000 2004 2
Slide 117: EVLP during pandemic
EVLP during pandemic • 2016 only 1% of Lung Txp was EVLP • 2020 25% of Lung Txp was EVLP • 1 of 4 programs >100 Lung Txp • Rationale for EVLP • Logistics • 3rd party recovery services • Marginal criteria assessment • Additional COVID testing In the future, these newer EVLP indications may be applica
Slide 118: Preclinical drug discovery
Preclinical drug discovery 118
Slide 119: Key take-aways: Lung
Key take-aways: Lung • EVLP is a safe and efficatious way to increase the number of life saving lung transplants • The pandemic has demonstrated that there are potential new indications for EVLP • EVLP growth is trending upward and is a standard practice in high performing lung transplant centers 11
Slide 120: Lung bioengineering
Lung bioengineering - Centralized Ex Vivo Lung Perfusion Brandi Zofkie, Director Lung Bioengineering
Slide 121: XVIVO Capital Markets Day September 2021
XVIVO CAPITAL MARKETS DAY SEPTEMBER 2021
Slide 122: Our Story
WHO WE ARE Our Story Parent Parent company company 1996 2006 2014 United Therapeutics Corporation was Under the name of Lung Rx, Lung Biotechnology Founded in 2014, Lung Bioengineering Inc. is a founded in 1996 by Martine Rothblatt was established in 2006 as part of United wholly-owned subsidiary of
Slide 123: Lung Bioengineering public benefit mission
As a wholly-owned subsidiary of a public benefit corporation, Lung Bioengineering (LBE) is committed to advancing transplantation science and technology in addition to providing a seamless centralized EVLP service model designed to maximize the potential for every organ to count towards saving patie
Slide 124: Challenges in Transplantation
WHAT WE DO Challenges in Transplantation LOGISTICAL CHALLENGES AND REMOVING BARRIERS AND PROVIDING INADEQUATE INFORMATION TOUCHPOINTS THROUGHOUT THE ENTIRE PROCESS The current process that precedes the acceptance of a Lung Bioengineering’s unique centralized Ex Vivo Lung lung for transplant is compl
Slide 125: What is a Centralized EVLP Service?
What is a Centralized EVLP Service? Lung Bioengineering’s centralized EVLP service model supports WHAT WE DO transplant centers by removing barriers and providing touchpoints at every step of the donation and transplantation process in order to optimize organ utilization. FIRST OF ITS KIND FACILITIE
Slide 126: LBE's Centralized EVLP Process
LBE's Centralized EVLP Process 01 02 03 WHAT WE DO 126
Slide 127: Benefits of LBE Centralized EVLP service
Benefits of LBE Centralized EVLP service ROBUST EXPERTISE REASONS TO BELIEVE FLEXIBILITY TRUSTWORTHY DATA EXPANDED DONOR POOL RESOURCE SAVINGS RISK MANAGEMENT CONTINUOUS LOGISTICAL ASSISTANCE LBE SEAMLESS SERVICE 127
Slide 128: Our EVLP procedure figures
Our EVLP procedure figures* as of September 16th, 2021 291 DONOR LUNGS AT LB1 IN SILVER SPRING, MD & LB2 IN JACKSONVILLE, FL 188 EVLP LUNGS REASONS TO BELIEVE ACCEPTED TO TRANSPLANT 01 191 PATIENTS TRANSPLANTED WITH EVLP LUNGS LBE ROBUST Collective experience of our team SEAMLESS EXPERIENCE 100+ SER
Slide 129: Our EVLP team
OUR EVLP TEAM UNRIVALLED REASONS TO BELIEVE EXPERIENCE 24/7/365 LBE AVAILABILITY SEAMLESS SERVICE BENEFITS QUALITY ASSURANCE 129
Slide 130: Optimized decision making
OPTIMIZED DECISION MAKING Extended preservation time provides transplant clinicians with additional opportunities to: • evaluate lung viability • ensure donor compatibility REASONS TO BELIEVE while removing some of the resource burden on transplant center staff when lungs become available. 02 SINGLE
Slide 131: Remote real-time data
REMOTE REAL-TIME DATA The case management exchange (XMX) provides transplant physicians with real- time data that is viewable remotely from any location and on any mobile device (including cellphones and tablets). ENHANCED INSIGHT & COMMUNICATION REASONS TO BELIEVE Live video and continuous data sha
Slide 132: LBE Access XMX
REASONS TO BELIEVE LBE ACCESS XMX SEAMLESS SERVICE ANYWHERE & BENEFITS ANYTIME VIA INTERNET CONNECTION 132
Slide 133: Access to additional donor lungs
ACCESS TO ADDITIONAL DONOR LUNGS EVLP allows for consideration of lungs that once would have gone unused, such as those with limited or suspect functional data, or from more distant REASONS TO BELIEVE donor hospitals. 04 MULTIPLE EVLP PROCEDURE ROOMS EXPANDED LBE has two centers with four devices, e
Slide 134: Our facilities
OUR FACILITIES REASONS TO BELIEVE ü CONTROLLED SILVER SPRING, MD ENVIRONMENT 28,000 ft2 facility | Six procedure rooms ü IN-HOUSE MATERIALS LBE SEAMLESS AND INVENTORY SERVICE BENEFITS ü FACILITIES WITH AV INTEGRATION ü 24/7/365 AVAILABILITY JACKSONVILLE, FL 25,000 ft2 facility | Three procedure room
Slide 135: Reduction of resource burden
REDUCTION OF RESOURCE BURDEN REASONS TO BELIEVE Lung Bioengineering’s centralized EVLP model reduces the resource burdens experienced with in- house EVLP which include: 05 • Costs of personnel, training, and equipment • Technical issues that can occur during learning curve of training or in circumst
Slide 136: Facilitation of further evaluation
FACILITATION OF FURTHER EVALUATION Lungs are assessed in an ex vivo REASONS TO BELIEVE environment which allows for the gathering of information that may not be available in the ICU. This means that lungs can be sent 06 for further evaluation, even on short notice, and provides transplant physicians
Slide 137: Continuous expert support
CONTINUOUS EXPERT SUPPORT REASONS TO BELIEVE LBE’s experienced EVLP Specialists understand the medical management of 07 donor lungs, the allocation system, and transportation logistics and are on hand to offer support throughout the EVLP process. LBE CONTINUOUS SEAMLESS SERVICE LOGISTICAL BENEFICIAL
Slide 138: Lung Bioengineering 360°
Lung Bioengineering 360° THE FUTURE OF OUR CENTRALIZED EVLP MODEL As we work towards the future, we are WHAT WE DO expanding our capabilities to deliver a true 360-degree service model for EXPANSION INCREASE IN OF ORGAN NUMBER OF organ transplantation. This model will PERFUSION EVLP encompass hearts
Slide 139: Thank you
THANK YOU 139
Slide 140: Future of transplantation
Future of transplantation Christoffer Rosenblad, COO
Slide 141: Megatrends in transplantation
Megatrends in transplantation New business Bioprinting models Xeno- Digitalization transplantation 141
Slide 142: Xenotransplantation
Xenotranplantation Prof. Muhammad M. Mohiuddin University of Maryland School of Medicine
Slide 143: Cardiac Xenotransplantation
Cardiac Xenotransplantation Muhammad Mansoor Mohiuddin, MBBS Professor of Surgery Director, Program in Cardiac Xenotransplantation Department of Surgery, Division of Cardiac Surgery University of Maryland School of Medicine Baltimore, Maryland, USA 143
Slide 144: Normal Xenograft
) [ 144 UNIVERSITY ef MARYLAND SCHOOL OF MEDICINE Normal Xenograft
Slide 145: Hyper Acute Xenograft Rejection (HAR) Within Minutes
Hyper Acute Xenograft Rejection (HAR) Within Minutes 145
Slide 146: Orthotopic Tx
Orthotopic Tx Donors Recipients Orthotopic cardiac Specific Pathogen Free (SPF) (15-30 Kg) transplantation (15-30 Kg) Genetic Immune engineering modulation 146
Slide 147: Orthotopic Transplant
) [ 147 UNIVERSITY ef MARYLAND SCHOOL OF MEDICINE Orthotopic Transplant
Slide 148: Postoperative Cardiac Xenotransplant Function
Postoperative Cardiac Xenotransplant Function 148 Coming off of bypass
Slide 149: Postoperative Cardiac Xenotransplant Function
Postoperative Cardiac Xenotransplant Function 149 5 hours post-bypass
Slide 150: Model
Model Orthotopic transplant XVIVO Heart Box Thanks to Prof. Bruno Reichart' s Group 150
Slide 151: Methods
Methods • Donor genetically modified cardiac xenografts from landrace pigs were transplanted into Papio albus recipients. • After procurement and prior to transplantation, one of the following induction/preservation techniques were employed: 151
Slide 152: Methods
Methods Support Scale 1 2 3 4 5 Inotropes: Epinephrine (mcg/kg/min) 0.01-0.05 0.06-0.01 0.11-0.15 0.16-0.20 > 0.20 Dobutamine (mcg/kg/min) 2.5-6.9 7.0-11.4 11.5-16.9 16.0-20.4 > 20.4 Milrinone (mcg/kg/min) 0.125-0.24 0.250-0.374 0.375-0.49 0.5-0.624 > 0.624 Vasopressors: Norepinephrine (mcg/kg/min)
Slide 153: Results
Results Donor Recipient Genetics Preservation Type weight (kg) weight (kg) GTKO.B4KO.hCD46.hTBM.hEPCR.hCD47.hHO1.hVWF 21 25 GTKO.hCD46.hTBM.hCD47.hEPCR.hHO1 10 10 GTKO.hCD46.hTBM.hCD47.hEPCR.hHO1 23 21 Crystalloid GTKO.hCD46 13 13 Induction with GTKO.B4KO.hCD46.hHLAE Slush Storage 9 10 GTKO.CMAHKO.h
Slide 154: Results
Results Preservation % Surpassed Total Peak Peak Base % Extubated Peak pH Type PCXD Support Lactate Deficit Traditional (n=8) 0.0% 0.0% 6.4 ± 2.8 14.3 ± 1.7 12.5 ± 4.9 7.19 ± 0.1 Blood Cardioplegia 66.7% 66.7% 3.0 ± 2.6 3.6 ± 0.0 4.3 ± 3.0 7.29 ± 0.2 (n=3) NICP (n=5) 100.0% 80.0% 2.0 ± 1.9 3.5 ± 1.5
Slide 155: Blood cardioplegia and XHS (NICP) overcome PCXD
Blood cardioplegia and XHS (NICP) overcome PCXD Compared to Crystalloid Cardioplegia • Blood Cardioplegia/NICP (Steen) better than crystalloid cardioplegia • Primary end point: surpassed PCXD (dotted line) • Secondary end point: amount of support required, metabolic derangements 155 Goerlich, C. E.
Slide 156: Blood cardioplegia and XHS (NICP) overcome PCXD
Blood cardioplegia and XHS (NICP) overcome PCXD Compared to Crystalloid Cardioplegia • Blood Cardioplegia/NICP (Steen) better than crystalloid cardioplegia • Primary end point: surpassed PCXD (dotted line) • Secondary end point: amount of support required, metabolic derangements 156 Goerlich, C. E.
Slide 157: Survival-Based on Preservation
) [ UNIVERSITY ef MARYLAND SCHOOL OF MEDICINE Survival-Based on Preservation 100 Probability of Survival 3 oY 0 100 200 300 Survival (days) + XHS + Other
Slide 158: Results: Graft Survival
) [ UNIVERSITY ef MARYLAND SCHOOL OF MEDICINE > Results: Graft Survival 100+ : 2 g 50- + Group 1: non-GHRKO with CMAHKO (n=2) na 4 —- Group 2: GHRKO, non-CMAHKO (n=2) —— Group 3: GHRKO and CMAHKO (n=4) 0 roe oes 0 100 20 300 Time (days)
Slide 159: Conclusions
Conclusions • Graft survival is minimal with conventional methods of cardioplegia and preservation • PCXD limits graft survival beyond 48 hours • All transplants performed with XVIVO XHS and heart box overcame PCXD • Heart Xeno and Allografts after NICP did not require any inotropic support and had
Slide 160: XenoHeart Team
XenoHeart Team Program Director Perfusionists Veterinarian Muhammad M Mohiuddin Brian McCormick Ivan Tatarov Brian Donahue Surgeon Cardiac Transplant Surgeons Alyssa Yurek Tianshu Zhang Bartley Griffith Nursing and OR Staff Animal Supervisor David Kaczorowski Lauren Szostek Billeta Lewis Immunologis
Slide 161: Thanks
) [ UNIVERSITY ef MARYLAND SCHOOL OF MEDICINE Thanks
Slide 162: Key take-aways: Future of transplantation
Key take-aways: Future of transplantation • Today 10% of the total need for organ transplant is met • Machine perfusion is proven to increase the number of transplantable organs • New business models and Innovation e.g. Xeno transplantation will play a vital role to one day accomplish our vision tha
Slide 163: Q&A
Q&A
Slide 164: Thank you
Thank you Dag Andersson, CEO
Slide 165: In summary
In summary • A global organ shortage • Focus on organ utilization is increasing • Machine perfusion recognized as the enabler to drive utilization • XVIVO has a unique range of products for all major organs • Execution of our five strategic focus areas will make us the global leading ‘all organ’ com
Slide 166: Nobody should die waiting for a new organ
Nobody should die waiting for a new organ
Slide 167: Thank you!
Thank you!
Slide 168: Glossary
Glossary Clinical study / trial FDA or US Food and Drug Administration A study in healthy or sick people to study the effect of a drug or The FDA is the US’s food and drug authority with responsibility for treatment method. food, dietary supplements, drugs, cosmetics, medical equipment, radiology eq
Slide 169: Glossary
Glossary NEJM PMA or Premarket Approval New England Journal of Medicine. Premarket approval (PMA) is the FDA - process of scientific and regulatory review to evaluate the safety and efficacy of a medical NHSBT device. The NHS (National Health Service) Blood and Transplant in UK. Preclinical study NI