Immunic, Inc. · NASDAQ:IMUX
Immunic — Vital Therapies — Investor Presentation (October 2015)
79 slides from Immunic's investor presentation, Oct 16, 2015
Slide 1: Corporate Overview as of October 16, 2015
I a ~V~ VITAL THERAPIES’ TARGETING LIVER DISEASE Corporate Overview as of October 16, 2015
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation are forward-looking statements, including, among others, statements relating to plans and objectives of management for future oper
Slide 3: Table of Contents
Table of Contents |. Overview Il. Investment Highlights lll. The ELAD System lV. VTI-208 Trial Results and the Path Forward V. Market Opportunity for ELAD VI. Background: Financial, Management and Board Vil. Key Challenges VIII. Review of Highlights IX. Appendix 3 SS vita
Slide 4: VTI-208 Overall Intent-to-Treat (ITT) Did Not Work
VTI-208 Overall Intent-to-Treat (ITT) Did Not Work August 21, 2015 Announcement: VTI-208, a randomized, controlled open label phase 3 trial in subjects with alcohol-induced liver decompensation (AILD) did not achieve its primary (Kaplan Meier survival analysis through at least day 91) or secondary (
Slide 5: VTI-208 Subset of MELD < 28
VTI-208 Subset of MELD < 28 Apre-specified subset analysis of subjects with baseline MELD Score less than 28 revealed a strong trend in overall survival favoring ELAD (p=0.077, non-significant or NS)". 100 90 20 & rs Z p=0.07 Bs HR=0.575 3 ELAD N=51 a Control N=69 a Total N=120 g 5 30h a 20h. of ———
Slide 6: VTI-208 Subset of Subjects Below Median Age
VTI-208 Subset of Subjects Below Median Age A pre-specified subset analysis of subjects with age less than the median (46.9 years) revealed a trend in overall survival favoring ELAD (p=0.167, NS)". 100 30 80 vol. Control N=58 Total N=101 ‘Survival probability (%) ELAD toh. ‘| Control re 1. 1. A ° 10
Slide 7: VTI-208 Post-Hoc Analysis: Overall Survival, ITT population
VTI-208 Post-Hoc Analysis: Overall Survival, ITT population, Age <50, MELD <30, INR $2.5, Creatinine <1.3, Bilirubin 216 Apost-hoc subsetanalysis of 60 subjects with baseline age < 50, MELD < 30 and further restrictions on MELD components creatinine < 1.3 mg/dL, INR $2.5 and bilirubin = 16 mg/dL thr
Slide 8: The Path Forward: Anticipated Next Steps
The Path Forward: Anticipated Next Steps GOAL: Complete a successful phase 3 confirmatory trial focused on the type of subjects who appear to have responded to ELAD in VTI-208 TIMELINE: Q4:2015 Briefing Document for Proposed VTL-308 trial design sent to FDA Confer with FDA Presentation of VTI-208 re
Slide 9: The Path Forward: Proposed Confirmatory Trial
The Path Forward: Proposed Confirmatory Trial GOAL: Modify as little as possible from VTI-208 to create a confirmatory trial focusing on most promising population * Focus on sites with VTI-208 experience in US and Europe (40 sites enrolled subjects) * Narrowing of eligibility based on age, MELD and
Slide 10: Hypothesis of ELAD Mechanism of Action
Hypothesis of ELAD Mechanism of Action* The ELAD System contains over one hundred billion human liver-derived cells which are believed to perform key aspects of liver function in response to patient-specific stimuli. These functions include: * Modulation of inflammation, which is thoughtto be a majo
Slide 11: Acute Liver Failure: A Significant Market
Acute Liver Failure: A Significant Market + Estimated 80,000 patients in the US and Europe with addressable forms of liver failure: predominantly alcohol-induced liver decompensation + Expert consultant recommended price range from $150 to $275K for ELAD: - Substantial pricing precedence with orphan
Slide 12: Investment Highlights
Investment Highlights ELAD: Bio-artificial liver system designed to improve overall survival in acute forms of liver failure, incorporating hundreds of billions of human liver-derived cells - Orphan Biologic in United States and Europe — Research shows performance of key aspects of liver function, i
Slide 13: Investment Highlights
Investment Highlights Unique market position - No known bio-artificial liver competitors in clinical trials in US or EU - Key US patent into April 2027; follow-on applications pending — Orphan designation provides market exclusivity of 7 years in the US and 10 years EU, if first to market - |fapprov
Slide 14: ELAD System: Bio-artificial liver system designed to improve overall survival
ELAD System: Bio-artificial liver system designed to improve overall survival in acute forms of liver failure The ELAD System is limited by federal law to investigational use only, and is not approved for commercial distribution. S$ VITAL THERAPI
Slide 15: The ELAD System
The ELAD® System Bio-artificial liver system designed to improve survival in acute forms of liver failure Combination product regulated as a biologic by FDA (CBER*); ATMP* by EMA Allogeneic cellular therapy: continuous treatment for 3 to 5 days 440g of immortal human C3A liver-derived cells — Four c
Slide 16: Key Differentiator: Human Liver-Derived C3A Cells
Key Differentiator: Human Liver-Derived C3A Cells Allogeneic cellular therapy based on VTL C3A cells — Human No animal safety issues with the cells — Scalable Can be grown in large quantities — Allogeneic Simpler than autologous therapies — — Stable ‘Can be maintained for 50 days; shipped up to 60 h
Slide 17: New Phase Program to be Guided by Large Clinical Data Subset
New Phase 3 Program to be Guided by Large Clinical Data Subset $< VITAL THERAPIES
Slide 18: VTI-208 Results Inform Future Phase Design
VTI-208 Results Inform Future Phase 3 Design + VTI-208: phase 3 randomized, controlled, open-label trial in subjects with alcohol-induced liver decompensation (AILD) enrolled 203 subjects — Primary endpoint: Kaplan Meier overall survival through at least 91 days — Secondary endpoint: proportion of s
Slide 19: VTI-208 Safety Profile
VTI-208 Safety Profile * Treatment emergent serious adverse events (TESAEs) were similar between the treated and control groups Safety Population ELAD Control 5 08 n n n Number 73 (768) 75 (69.4) 148 (72.9) Reporting Any TESAE Number of TESAEs 156 168 324 ELAD Control Total (N=95) (N=108) (N=203) Pr
Slide 20: VTI-208 Revealed Two Very Different Responses to ELAD
‘Survival probability (%) VTI-208 Revealed Two Very Different Responses to ELAD Overall Survival, ITT Population *| p=0.904 ‘| Ret 027 ELAD N96 “ Control e107 Tota W203 er 8 Days ELAD Control ‘Sunival probability (%) : Pre-specified Exploratory Analysis Based on MELD — = Overall Survival, MELD <28 D
Slide 21: ELAD Outcomes varied significantly by MELD Score
ELAD Outcomes varied significantly by MELD Score ELAD Response Determined by MELD Category: MELD Score <28 MELD Score 228 ELAD Treatment ‘Control ELAD Treatment Control Survival Estimates (N=51) (N=69) (N=45) (N=38) Number (%) Subjects who Died 45 (29.4) 30 (43.5) 34 (68.9) 21 (55.3) ‘Stil Alive 35
Slide 22: MELD is Clinically Validated
MELD is Clinically Validated The Model for End-stage Liver Disease (MELD) score is the most widely used and validated predictor of 90-day mortality in liver failure. MELD = _ 3.78xIn[serum bilirubin (mg/dL)] + 411.2xIn[INR] + 9.57xIn[serum creatinine (mg/dL)]. MELD was pre-specified subgroup paramet
Slide 23: Creatinine Analysis Helps Explain MELD Finding
Creatinine Analysis Helps Explain MELD Finding + Subjects with poor kidney function (high creatinine levels) appear not to tolerate ELAD: Creatinine < 1.5 mg/dL Creatinine 2 1.5 mg/dL ELAD Control ELAD Control Survival Estimates (N=78) | _(N=92) (N=18) (N=15) Number (%) of Subjects Died 33(429) | 44
Slide 24: INR Analysis Helps Explain MELD Finding
INR Analysis Helps Explain MELD Finding + Subjects with high INR levels appear not to tolerate ELAD: INR $2.5 INR > 2.5 ELAD Control ELAD Control Survival Estimates (N=80) (N=87) (N=16) (N=20) Number (%) of Subjects Died 34 (425) | 431494) | 12076.0) | 8(40.0) ‘Still Alive 45 (56.3) | 42(483) | 4(25
Slide 25: VTI-208 Revealed Two Very Different Responses to ELAD
VTI-208 Revealed Two Very Different Responses to ELAD Overall Survival, ITT Population px0.908 Ret 027 r ELAD N=95 ControiN=107 me Total N=203 ob a a a a a a a) Days ELAD Control -_ Pre-specified Exploratory Analysis Based on Age Overall Survival Age < Median 0.167 HRe0 634 ELAD N83 ControlN=58 Tota
Slide 26: ELAD Outcomes Varied by Age
ELAD Outcomes Varied by Age ELAD Response by Age Category: ‘Age <median ‘Age 2 median ELAD Treatment ‘Control ELAD Treatment Control ‘Survival Estimates (N=43) (N=58) (N=53) (N=49) Number (%) of Subjects Died 44 (32.6) 26 (44.8) 32 (60.4) 25 (51.0) Still Alive 29 (67.4) 32 (55.2) 21 (39.6) 24 (49.0)
Slide 27: Younger Patients Fared Better on ELAD Treatment
Younger Patients Fared Better on ELAD Treatment « A key observation from VTI-208 is that younger patients experience better outcomes on ELAD treatment — Younger patients are believed to have more regenerable livers’ — Older patients may be more likely to have undetected cirrhosis? — Older patients m
Slide 28: VTI-208 Post-Hoc Analysis: Overall Survival, ITT population
VTI-208 Post-Hoc Analysis: Overall Survival, ITT population, Age <50, MELD <30, INR $2.5, Creatinine <1.3, Bilirubin 216 Apost-hoc subset analysis of 60 subjects with baseline age < 50, MELD < 30 and further restrictions on MELD components creatinine < 1.3 mg/dL, INR < 2.5 and bilirubin > 16 mg/dL t
Slide 29: VTI-208 Insights
VTI-208 Insights « Although VTI-208 trial failed to achieve its primary endpoint, we believe it... — Provides key insights into most promising population for ELAD: + ELAD outcome appears better in those with baseline MELD Scores less than 28 — Subjects with creatinine < 1.3 mg/dL had better survival
Slide 30: Potential Multi-Billion Dollar Addressable Market
Potential Multi-Billion Dollar Addressable Market Noe VITAL THERAPIES
Slide 31: Acute Liver Failure: A Significant Market
Acute Liver Failure: A Significant Market * Sizeable market for orphan indication(s)*: AILD Fulminant Hepa‘ Surge! Failure Acute Liver Failure United States 30,000 2,000 10,000+ 40,000+ validated validated estimated Europe’ 30,000+ 2,000+ 10,000+ 40,000+ estimated —_ estimated estimated * MELD and a
Slide 32: Market Size Impact
Market Size Impact + Does lower MELD lead to a smaller market? - InAILD, MELD progresses from normal to mid-20’s and above over the course of weeks / months + Patients with MELD > 28 typically had a MELD < 28 several weeks beforehand — MELD restriction requires capturing patients earlier + More proa
Slide 33: ROW Also Presents Large Opportunity
ROW Also Presents Large Opportunity + ELAD market in ROW anticipated to focus on future indications: * Acute flares of viral hepatitis (see VTIC-301 for clinical data) + Supporting resections of liver cancer (anecdotal evidence from compassionate use; formal trial would likely be required) + Large p
Slide 34: Pricing Flex
Pricing Flex + MME has provided reimbursement support — Completed>125 US and EU launch price strategies in the last 3 years - Vast orphan drug experience, assisting clients with > 20 ultra-orphan compounds in> 30 disease states across > 40 countries + MME recommended price range from $150 to $275K f
Slide 35: Liver Transplant Cost / Benefit
Liver Transplant Cost / Benefit + Costof approximately $577,100in 2011 for7 months surrounding transplant (and can total over $1 million over the life of a patient’): - Inaddition $40K per year for immunosuppression alone; high risk of cancer, infection, kidney failure Transplant Physician __180-day
Slide 36: ELAD Presents Potential Multi-Billion Dollar Opportunity
ELAD Presents Potential Multi-Billion Dollar Opportunity Estimated annual addressable market in US & EU 80,000 patients Preliminary pricing guidance of $150,000-$275,000* Total market size (using low end of preliminary price guidance) estimated to be roughly $12 billion Reduction in market size due
Slide 37: Unique Market Position
Unique Market Position
Slide 38: Intellectual Property and Exclusivity
Intellectual Property and Exclusivity Patent Protection MT - KeyU.S. Patent Issued in 2012, term to April 2027 o United Sates Patent gormanas_ Uskgaant + Covers use of the C3A celMline in ELAD System to treat liver sr ere ONES RE failure ao cee — December 2013 patent covers bedside unit; term to May
Slide 39: Financial Summary
Financial Summary $< VITAL THERAPI
Slide 40: Cash Position and Cap Table
Cash Position and Cap Table Cash Position Capitalization Table Common shares outstanding Options outstanding Total Other Options available for grant Warrants (average exercise price of $95.21, expiring between February 2016 and September 2019) Cash of $63 million as of August 31, 2015 As of October
Slide 41: Team
Team
Slide 42: Executive Team with Operational Experience
Executive Team with Operational Experience Tecty Winters, ERD = MortnoLoaic" ceo Rob Ashley, MA EVP /CTO Amersham Duane Nash, MD, JD, MBA STARMINE Evp / CBO ransplantexperience at Michael Swanson, MBA Gee a a ate amira > PROMETHEUS Jan Stange, MD 10 Andrea Loewen Baxter VP, Regulatory sere = Biogen
Slide 43: Strong Board of Directors
Strong Board of Directors Muneer A. Satter Co-Chairman/Lead Terry Winters, PhD Co-Chairman Jean-Jacques Bienaimé Philip Croxford, BPh Cheryl Cohen Doug Godshall Errol Halperin, JD, LLM Lowell Sears Randolph Steer, MD, PhD Chairman - Satter Investment Mgmt.; Chairman — Akebia Therapeutics Former part
Slide 44: World-Class Clinical Advisory Boards
World-Class Clinical Advisory Boards UNITED STATES Michael Millis, MD, Chief of Transplant, University of Chicago — CHAIRMAN Robert Brown, MD, MPH, Director of Center for Liver Disease and Transplantation, Columbia University Steve Conrad, MD, PhD, Director of Critical Care, Louisiana State Universi
Slide 45: Key Challenges
Key Challenges 1. ELADis notyetproventowork: Our VTI-208 trial failed to achieve its primary and secondary endpoints, and ELAD has not yet been proven to be effective and safe based on prospectively defined criteria in a US or European trial. This evidence will be necessary for future commercializat
Slide 46: Investment Highlights
Investment Highlights ELAD: Bio-artificial liver system designed to improve overall survival in acute forms of liver failure, incorporating hundreds of billions of human liver-derived cells - Orphan Biologic in United States and Europe — Research shows performance of key aspects of liver function, i
Slide 47: Investment Highlights
Investment Highlights Unique market position - No known bio-artificial liver competitors in clinical trials in US or EU - Key US patent into April 2027; follow-on applications pending — Orphan designation provides market exclusivity of 7 years in the US and 10 years EU, if first to market - |fapprov
Slide 48: APPENDIX
APPENDIX §X VITAL THERAPIES
Slide 49: Additional VTI-208 Post Hoc Subset Analyses
Additional VTI-208 Post Hoc Subset Analyses 3S VITAL THERAPIES
Slide 50: Overall Survival, ITT population, including VTI-208E through 7/30/15
Overall Survival, ITT population, including VTI-208E through 7/30/15 Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 ELAD Treatment Control ‘Survival Estimates (N=29) (N=31) Number (%) of Subjects who Died 6 (20.7) 16 (51.6) Number (%) of Subjects Censored 23.793) 45 (48.4) Censored re
Slide 51: Overall Survival, ITT population, including VTI-208E through 7/30/15
Overall Survival, ITT population, including VTI-208E through 7/30/15 Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 mary of Kapha Mei Anse of reall Srv for Saji wih ep S0, MELD<30,By=16,INRe2 Sand Cratne<l.3 Trt Popa LAD mametste>) Ceara 2 OO MEAD Teva Supe Cond 3 BOBeew xen cewend ro
Slide 52: Overall Survival, ITT population, up to Study Day 91
Overall Survival, ITT population, up to Study Day 91 Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 ELAD Treatment Control Survival Estimates (N=29) (N=31) Number (%) of Subjects who Died 2(69) 12 (38.7) Number (%) of Subjects Censored 27 (93.1) 19 (61.3) Censored reason: Still Alive
Slide 53: Overall Survival, ITT population, up to Study Day 91
Overall Survival, ITT population, up to Study Day 91 Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 ‘Samar of Kaplan-Meier Arabs of Overall Survalup to Suady Dey Difor Subjects vith Age 50, MELLD<30,.Bilb=16,INR<=2 5 and Crestinine=13 TrTPopulasn (== bo —con(3¥31) ‘pavia Dienioaion s
Slide 54: Proportion of Survivors at Study Days 28 and 91
Proportion of Survivors at Study Days 28 and 91 Age < 50, MELD<30, Bili>=16, INR<=2.5 and Creatinine<1.3 ELAD Treatment Control Total Characteristic (N=29) (N=31) (N=80) ‘Study Day 28 Number(%) of Subjects who Died 1eG Por ces Number (%) of Subjects Stil Alive 28 (988) 2767.1) 55(917) pevalue [1] 0.
Slide 55: Demographics (1): Age < 50, MELD<30, Bilirubin>=16
Demographics (1): Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 ELAD Treatment Control Total Characteristic (N=29) (N=31) (N=60) Randomization Stratum, n (%) ‘Subjecthas AILD thatis classified as severe Acute AlcoholicHepatitis 28 (26.6) 28 (903) 56 (93.3) Subjecthas AILD thatisnot c
Slide 56: Demographics (2): Age < 50, MELD<30, Bilirubin>=16
Demographics (2): Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 ELAD Treatment Control Total Characteristic (N=29) (N=31) (N=60) Height (cm) [1] n 25 30 55 Mean (SD) 168.5 (10.34) 172.3(10.98) 170.5 (10.76) Median 167.0 173.0 170.0 Min, Max 152, 200 150, 193 150, 200 ‘Weight (kg) [1]
Slide 57: Liver disease characteristics (1)
Liver disease characteristics (1): Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 ELAD Treatment Contr Total Characteristic (e29) (ve31 (60) pevalie Medical treatments at Baseine, n(%): Steroids 16 (652) 19613) 35683) 0631 Pentoxtylne 910) 1155) 20333) o715 Neacetyboystene 269) 265) 4
Slide 58: Liver disease characteristics (2)
Liver disease characteristics (2): Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 ELAD Treatment Control Total Characteristic (=23) (v=31) (=60) pwalue Subject had dialysis at least twice in the past week. n (%) Yes 0 0 0 No 29 (100) 31 (100) 60 (100) Baseline Maddrey Discriminant Fun
Slide 59: Liver disease characteristics (3)
Liver disease characteristics (3): Age < 50, MELD<30, Bilirubin>=16, INR<=2. 5 and Creatinine<1.3 ELAD Treaiment Conta ——Tet " : Characteriste_ i=29) (W=31) W=60) . (On renal replacement therapy (hemodialysis, CVVHD, CVVH, peritoneal, tc) at randomization, n (%) ‘Yes ° ° ° No 29100) 34 (100) 60 (100
Slide 60: Safety Summary: Age < 50, MELD<30, Bilirubin>=16
Safety Summary: Age < 50, MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 ELAD Treatment Control Total Characteristic (N=30) (N=30) (N=60) Number (%) of Subjects Reporting Any TEAE 30 (100) 30 (100) 60 (100) Number of TEAES 547 494 1041 Number (%) of Subjects Reporting Any TESAE 20 (68.7) 18 (60
Slide 61: VTI-208 Bilirubin Percentage Change
VTI-208 Bilirubin Percentage Change - ITT, N=203 MELD<28, N=120 Control ELD 100% os ay PS oS NY dP e grdoroty soot Ay PPot om esis s os ery ay ‘Soe 3 MELD<30, age<50, INR<=2.5, Cr<1.3, Bili>=16, N=60 20% 0% 20% 40% 60% Control 80% ED ee we a ey &. be se aah
Slide 62: VTI-208: Subjects Experiencing at least 20% Reduction in Bilirubin
VTI-208: Subjects Experiencing at least 20% Reduction in Bilirubin ITT Overall MELD<28 Overall Chi-square Chi-square Total Alve %ANe = Dead «LTFU OP Total Alve %AlNe Dead LTFU Bil>=20% 99 63 GMN7(65%) 34 2 l>=20% 5045 4e69(am) 141 Bili<20% S| ees | eee 61 30 36161%) 391 10.0028 MELD<28 Control ITT C
Slide 63: Overall Survival for MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3
Overall Survival for MELD<30, Bilirubin>=16, INR<=2.5 and Creatinine<1.3 N=102 Cases summary Number of events Number censored ® Factor N N % 24 44.44 | ELAD 33 68.75 Overall 57 55.88 i Comparison of survival curves (Logrank test) Chi-squared 7.3159 DF 1 Significance P = 0.0068 Hazard ratios* with 95
Slide 64: Additional VTI-208 Information
Additional VTI-208 Information $< VITAL THERAPIES
Slide 65: VTI-208 Clinical Trial Sites
VTI-208 Clinical Trial Sites Number of subjects enrolled by site rx Pa PEE LOSS OLS MOIOED SE LS LAE LOO A d cs
Slide 66: Prior Clinical Data Lend Support to VTI-208 Subset Analysis
Prior Clinical Data Lend Support to VTI-208 Subset Analysis ee VITAL THERAPIES
Slide 67: Transplant Free Survival (proportion)
Transplant Free Survival (proportion) China Trial*: Enrolled Younger, Lower MELD Subjects Kaplan-Meier Plot of Transplant-Free Survival 5-year Follow up 100 1 ~ x, oe 0. S 8 8 5 2 sth 20.027 (Log-rank) a = oof] b. : ge 0. & 4 Par) 3 a 2 2 | p< 0.05, Wilcoxon nao? Ex a] nzas Control 10 ° soo tooo 380
Slide 68: China Data (VTIC-301) Distribution at Baseline
China Data (VTIC-301) Distribution at Baseline China: MELD analysis is consistent with VTI-208 MELD < 28 MELD 2 28 ‘Alive Dona | frramplar Ta ee Treated a 15 (71.4%) 5 (23.8%) 1 (4.8%) d 11 6 (54.5%) 5 (45.5%) 0 Control 9 5 (55.6%) 2 (22.2%) 2 (222%) Control 8 2(25%) 337.5%) 3(37.5%) China: very few
Slide 69: ELAD VTI-206: Trend to Increased Survival in AILD
ELAD VTI-206: Trend to Increased Survival in AILD 100 Overall survival: é 80 70 60 ‘Survival probabllity (%) 50 * Per protocol population (PP) acute lcohotec hepatitis (AAH) cohort (0-28) 40 Time (days) Baseline parameters comparison: VTI-206 PP vs VTI-208 MELD < 28 Cohort:* Baseline Parameter VTI-2
Slide 70: VTI-206 Data Distribution at Baseline
VTI-206 Data Distribution at Baseline VTI-206 PP AAH: MELD analysis is consistent with VTI-208 MELD < 28 MELD 2 28 Total | Alfro Sal] Dead | Trameplant Aliso] oscil | transplant Treated [ed 4(0%) —1:(20%) 0 Tr 8 4 (60%) 337.5%) 1.(125%) Control 3 1(33.3%) 2 (66.7%) 0 Control 3 6 (46.2%) 7 (53.8%) 0
Slide 71: ELAD Mechanism of Action Appendix
ELAD Mechanism of Action Appendix Research Shows Key Aspects of Liver Function
Slide 72: Hypothesis of ELAD Mechanism of Action
Hypothesis of ELAD Mechanism of Action* The ELAD System contains over one hundred billion human liver-derived cells which are believed to perform key aspects of liver function in response to patient-specific stimuli. These functions include: * Modulation of inflammation, which is thoughtto be a majo
Slide 73: Modulation of Liver Inflammation: International Liver Transplant Society (ILTS) 2015
Modulation of Liver Inflammation: International Liver Transplant Society (ILTS) 2015 AILD involves unregulated systemic inflammation’ and elevated plasma levels of inflammatory factors such as IL-1, IL-6, lipopolysaccharide (LPS), and TNF-a? Hepatocytes have been found to be a major source of acute-
Slide 74: Modulation of Liver Inflammation: ILTS 2015
Modulation of Liver Inflammation: ILTS 2015 VTL C3A cells have been shown in bench studies to secrete anti- iniammatory factors IL-1Raand AAT Constitutively - In response to co-incubation with IL-18 and IL-6. — Inresponse to LPS Response is dynamic - Temporal - Dose-dependent May contribute to the m
Slide 75: Support of Hepatocellular Metabolic Function: EASL 2015
Support of Hepatocellular Metabolic Function: EASL 2015 + Acute-on-chronic liver failure and acute liver failure are characterized by impaired liver function * Cell-based support of liver function could have therapeutic benefit if the cell therapy was demonstrated to provide metabolicfunctions requi
Slide 76: Support of Hepatocellular Metabolic Function: EASL 2015
Support of Hepatocellular Metabolic Function: EASL 2015 * Laboratory studies carried out by VTL show that C3A cells exhibit a diverse expression of various critical cytochrome P 450 isozymes including those involved in drug metabolism such as CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and CYP3AS. — The
Slide 77: Regeneration and Restoration of Liver Function: AASLD 2015
Regeneration and Restoration of Liver Function: AASLD 2015 a Liver has remarkable capacity for regeneration * VTL C3A cells produce several growth factors’ e.g.; — TGF-alpha — VEGF — HGF * Abstract accepted for poster presentation AASLD (November 2015) * Further work is aimed at understanding whethe
Slide 78: Mechanism of Action — Conclusion
Mechanism of Action — Conclusion * The precise mechanism of action for the ELAD System is unknown. * Laboratory studies conducted by VTL and presented at medical meetings suggest: — Simultaneous targeting of multiple processes associated with liver failure — Dynamic, patient specific responses * Fin
Slide 79: Vital Therapies: Targeting Liver Disease
XVsf -“Wr~ VITAL THERAPIES” TARGETING LIVER DISEASE
Vital Therapies — Investor Presentation (October 2015) on 6ix