Sequana Medical N.v · EURONEXT:SEQUA
Sequana Medical — Investor Presentation (October 2023)
68 slides from Sequana Medical's investor presentation, October 2023
Slide 1: Pioneers in the treatment of fluid overload
Pioneers in the treatment of fluid overload Transforming lives in liver disease, heart failure & cancer Investor presentation – October 2023 Euronext: SEQUA.BR
Slide 2: Disclaimers
Disclaimers Important Notice IMPORTANT: You must read the following before continuing. The following applies to this document, the oral presentation of the information in this document by Sequana Medical NV (the "Company") or any person on behalf of the Company, and any question-and-answer session t
Slide 3: Fluid overload – large markets with strong growth
Fluid overload – large markets with strong growth Poor clinical outcomes and high treatment costs when diuretics are no longer beneficial alfapump in liver disease DSR in heart failure • Market growing to over $2.5 billion by 2035(1) • Multi-billion market opportunity • FDA breakthrough device / App
Slide 4: Strong outlook for key value drivers
Strong outlook for key value drivers North American alfapump study – POSEIDON Liver disease / Q2 ‘23: H2 ‘23: Q4 ‘23: H2 ‘24: NASH Additional data Patient preference PMA submission Anticipated FDA at EASL & Matched registry* to FDA approval data 2023 2024 Q2 ‘23:Mid ‘23: Heart failure Q4 ‘23: H1
Slide 5: alfapump
alfapump® Proven step change in the treatment of liver refractory ascites
Slide 6: Refractory ascites – key complication of liver cirrhosis
Refractory ascites – key complication of liver cirrhosis Fatty liver disease / NASH is driving dramatic growth and change in attitudes to liver cirrhosis patients Viral infections (Hepatitis B & C) Non-Alcoholic Steatohepatitis Alcoholic Liver Disease (NASH/MASH) Liver Ascites Refractory cirrhosis A
Slide 7: Clear limitations of existing treatment options
Clear limitations of existing treatment options Little innovation or new development – transplant is a partner not competitor Paracentesis (LVP / drainage) Permanent Catheter System Painful, burdensome, short term benefit, QoL impact External Catheter, Risk for Infections / Blockage “Normal Life” TI
Slide 8: alfapump – continuous ascites removal to the bladder
alfapump – continuous ascites removal to the bladder Fully implanted automatic device for long term implantation Wireless battery charging Breakthrough Device Designation Settings wirelessly adjusted Remote data monitoring Moves up to 4 litres / day Over 1,000 systems implanted Strong IP barriers th
Slide 9: Large and strongly growing North American market
Large and strongly growing North American market NASH is forecast to drive significant growth for many years – and is changing attitudes to cirrhosis 3-5 paracentesis Priority market / year ~$500MM in 2025: 12+ paracentesis 78,000 / year patients with >$2.5 Bn recurrent or 6-7% CAGR refractory ascit
Slide 10: POSEIDON – Successful North American pivotal study
POSEIDON – Successful North American pivotal study Pivotal Cohort of 40 patients with recurrent or refractory ascites due to liver cirrhosis alfapump Primary Secondary Enrolment implantation endpoint endpoints 3 months 3 months 3 months // 18 months // Pre-implant Post-implant Post-implant Lon
Slide 11: Sustained effective control of ascites and robust safety profile at 12 months
Sustained effective control of ascites and robust safety profile at 12 months post-implant Virtual elimination of needle paracentesis • Maintaining 100% median per-patient reduction in therapeutic paracentesis (N=19, p<0.001)* Robust safety profile despite disease progression • 2 pumps explanted (
Slide 12: Clear US patient preference for alfapump vs SoC
Clear US patient preference for alfapump vs SoC Data from patient preference study and matched interim analysis of NACSELD registry with POSEIDON • US patients have a strong preference for the alfapump vs large volume paracentesis* • Reduction in paracentesis frequency and additional ascites good he
Slide 13: Attractive pricing with derisked reimbursement
Attractive pricing with derisked reimbursement Existing DRG payment and breakthrough device designation de-risk reimbursement of alfapump Coding – Strong existing position with potential for further upside • Existing US hospital DRG payment for alfapump procedure of $60-70K in target hospitals* • Su
Slide 14: US – Go direct to liver transplant centers
US – Go direct to 90 liver transplant centers Highly efficient approach to target doctors and patients – driven by treatment guidelines Cover 95% of liver transplants ~50 person commercial team Source: Organ Procurement & Transplantation Network, US Dept of HHS (optn.transplant.hrsa.gov) 14 14
Slide 15: DSR
DSR® Disease-modifying heart failure drug therapy tackling cardiorenal syndrome (CRS)
Slide 16: Cardiorenal Syndrome – key clinical challenge in HF
Cardiorenal Syndrome – key clinical challenge in HF Decongestion is a key component of CRS but the core therapy – loop diuretics – exacerbates the problem • Combined, and self-reinforcing dysfunction of heart and kidneys with hypothesised complex and interconnected mechanisms • Clinical profile thou
Slide 17: Congestion is key driver of morbidity & hospitalization
Congestion is key driver of morbidity & hospitalization Diuretic-resistance in heart failure is common and there are few effective clinical alternatives US hospitalizations HF hospitalizations annually due to ~1m 90% due to fluid overload heart failure (HF)(3) (AKA congestion)(3) c.5d Typical Annual
Slide 18: DSR (Direct Sodium Removal) – targets the key cause
DSR (Direct Sodium Removal) – targets the key cause Eliminating fluid spread across the body – working in partnership with the kidneys 1 Sodium-free DSR product 2 Sodium diffuses from 3 DSR product + extracted 4 Body eliminates free water administered to peritoneal body into DSR product sodium remov
Slide 19: Breaking the CRS vicious cycle & improving outcomes
Breaking the CRS vicious cycle & improving outcomes Detailed biomarker analysis aligns with improved clinical outcomes in RED DESERT and SAHARA Clinical proof-of-concept from RED DESERT and SAHARA studies Complete replacement of loop diuretics with safe, rapid and effective decongestion and mainten
Slide 20: DSR 2.0 improves therapeutic and safety profile
DSR 2.0 improves therapeutic and safety profile Strong granted IP drives high margin recurring revenue stream DSR 1.0 DSR 2.0 Sodium-free D10% (off-the-shelf) Sodium-free dextrose / icodextrin (proprietary) Clinical proof-of-concept Improved therapeutic profile Rapid clinical path Favorable
Slide 21: MOJAVE – Phase 1/2a randomized controlled US study
MOJAVE – Phase 1/2a randomized controlled US study Seeking to replicate RED DESERT and SAHARA positive results in US patients using DSR 2.0 4 weeks 3 months (initial follow-up at 30 days) DSR therapy (up to daily) + optimized usual care vs. Safety follow-up period IV loop diuretic + optimized usual
Slide 22: On track to start randomized cohort in Q1 2024
On track to start randomized cohort in Q1 2024 Top-line data from all three patients in non-randomized cohort planned by year-end • First 2 patients in non-randomized cohort successfully treated, without need for any loop diuretics • Both patients had heart failure with severe diuretic resistance at
Slide 23: Multi-billion commercial opportunity
Multi-billion commercial opportunity ~400K chronically congested HF patients hospitalized per year in the US and EU (“frequent flyers”) EU US $45K >$9 Bn 200K 200K US annual HF DSR addressable market patients patients hospitalization cost in US per patient Potential for premium DSR pricing through r
Slide 24: Outlook
Outlook Strong near term value drivers with clear long term potential
Slide 25: Strong outlook for key value drivers
Strong outlook for key value drivers North American alfapump study – POSEIDON Liver disease / Q2 ‘23: H2 ‘23: Q4 ‘23: H2 ‘24: NASH Additional data Patient preference PMA submission Anticipated FDA at EASL & Matched registry* to FDA approval data 2023 2024 Q2 ‘23:Mid ‘23: Heart failure Q4 ‘23: H1
Slide 26: Contact info
Contact info IR@sequanamedical.com +32 498 053579 www.sequanamedical.com
Slide 27: Back-up
sequanamedical
Slide 28: Sequana Medical NV
Sequana Medical NV Founded in 2006 Gent, Belgium (HQ): corporate, clinical, commercial Zurich, Switzerland: manufacturing, engineering, QA/RA ~60 employees Euronext Brussels: SEQUA 28 28
Slide 29: Strong organisation
Strong organisation Highly experienced leadership team supported by committed and well-reputed shareholders Executive team: Ian Crosbie Kirsten Van Bockstaele Oliver Gödje Dragomir Lakic Chief Executive Officer Chief Financial Officer Chief Medical Officer VP Manufacturing Gijs Klarenbeek Martijn Bl
Slide 30: Shareholders base and financial overview
Shareholders base and financial overview Ticker: SEQUA – Euronext Brussels • Outstanding shares: 28.2M • Outstanding shares corresponding to outstanding share options: 3.9M • Analysts: • Degroof Petercam – Laura Roba • Edison – Pooya Hemami • H.C. Wainwright – Yi Chen • KBC Securities – Jacob Mekhae
Slide 31: POSEIDON: Pivotal cohort
POSEIDON: Pivotal cohort alfapump therapy still ongoing at day 180 post-implant Actual data used Implanted with Evaluable for primary N = 26 Enrolled in alfapump effectiveness endpoint Pivotal Cohort at 6 months N = 71 Exited study prior to N = 40 N = 40 completing 6-month Pre-specified post-implant
Slide 32: POSEIDON: Pivotal Data - Patient profile
POSEIDON: Pivotal Data - Patient profile 40 severely decompensated patients – alcohol and NASH as key drivers of cirrhosis Age (mean) 63.6 ± 9.5 yr MELD score (mean ± SD) 15.2 ± 3.8 Cirrhosis etiology* - Alcohol - 47.5% - NASH - 37.5% - Viral hepatitis - 12.5% - Others - 11.0% TP per month prior to
Slide 33: POSEIDON: Primary effectiveness endpoints exceed predefined thresholds
POSEIDON: Primary effectiveness endpoints exceed predefined thresholds for study success* • 100% median per-patient reduction in therapeutic paracentesis (p<0.001)** • vs hypothesis of at least a 50% reduction • 77% of patients with at least 50% reduction in therapeutic paracentesis (p<0.001)** • vs
Slide 34: POSEIDON: Observed data through day 180 post-implant
POSEIDON: Observed data from patients completing alfapump therapy through day 180 post-implant* Distribution of reduction in Therapeutic Paracentesis post-implant vs pre-implant (Pivotal Cohort N = 26) * These observed patient data are not part of the main primary effectiveness endpoint analysis. 34
Slide 35: POSEIDON: Primary safety endpoint in line with expectations
POSEIDON: Primary safety endpoint in line with expectations* Primary safety endpoint (pivotal cohort N = 40): • Combined rate of i) open surgical re-intervention due to pump system-related AE or to restore pump functionality, ii) pump explant (without replacement) due to pump system-related AE, or i
Slide 36: POSEIDON: Similar number of MAEs pre vs post implant
POSEIDON: Similar number of MAEs pre vs post implant 3 months pre-implant 3 months post-implant (Day -90 to Day -1) (Day 91 to Day 180) No. of subjects with No. of subjects with No. of events No. of events events events Major Adverse Events 5 3 5 4 AKI > stage 2 0 0 1 1 Hepatorenal Syndrome 0 0 1 1
Slide 37: POSEIDON: Comparable number of serious infections pre vs post implant
POSEIDON: Comparable number of serious infections pre vs post implant 3 months pre-implant 3 months post-implant (Day -90 to Day -1) (Day 91 to Day 180) No. of subjects with No. of subjects with No. of events No. of events events events All Serious Infections 2 2 3 3 Of which: Ascites-Related Seriou
Slide 38: Despite AKIs, stable kidney function over long-term
Despite AKIs, stable kidney function over long-term • AKI events post-implant were manageable 6 months post-implant (Day 0 to Day 180) No. of events No. of subjects with events AKI stage 1 16 14 AKI 1 of limited clinical relevance AKI stage 2 4 4 AKI 2 and 3: three events resolved and three events w
Slide 39: POSEIDON: QoL assessment
POSEIDON: QoL assessment Two validated QoL methodologies are part of secondary endpoints • SF-36: • General health-survey questionnaire • Endpoint: improvement* in SF-36 Physical Component Score • Subdomains of Physical Component Score: physical functioning, role physical, bodily pain, general healt
Slide 40: QoL: Maintaining clinically meaningful improvement despite disease progression
QoL: Maintaining clinically meaningful improvement despite disease progression SF-36 Physical Component Score (higher is better): Ascites Q Score (lower is better): * * * * QoL: Quality of Life 40 40
Slide 41: SF-36 Physical Component Score is an independent predictor of mortality
SF-36 Physical Component Score is an independent predictor of mortality(1) Multicenter randomized controlled study in patients with recurrent (N=164) and refractory (N=241) ascites Patients stratified by survival 1 year after follow-up Cumulative all-cause mortality for patients below or above Physi
Slide 42: Over 70% survival at 12 and 18 months post-implant
Over 70% survival at 12 and 18 months post-implant Compares favorably to literature citing only ~17% predicted survival at 12 months and ~5% at 18 months(1) Note: POSEIDON study not powered for survival Source 1: Salerno et al., Gastroenterology 2007; 133:825-834; predicted survival probability for
Slide 43: Patient preference study completed
Patient preference study completed Recommended study by FDA to elicit patient preference for attributes of an implantable pump as a novel interventional treatment for ascites • Rigorous study design pre-discussed with FDA: • Survey using discrete-choice experiment (DCE*) methodology conducted by RTI
Slide 44: Study indicates profile exceeding patient expectations
Study indicates profile exceeding patient expectations Patient preference study indicates compelling profile for alfapump Patient preference study POSEIDON pivotal cohort Risk tolerance (over 6 months) Maximum acceptable risk Observed rate Major surgery or death >10% 0% Minor procedure >35% 20% Seri
Slide 45: Data support alfapump as a desirable treatment option
Data support hypothesis that alfapump is a desirable treatment option for the majority of patients Reduction in paracentesis frequency and additional ascites good health days are important attributes for a novel interventional treatment for ascites. Patients responded with a 65% likelihood of sele
Slide 46: Matched cohorts: NACSELD registry vs POSEIDON
Matched cohorts: NACSELD registry vs POSEIDON Comparing outcomes of POSEIDON pivotal cohort to matched patient group from NACSELD registry • Consortium of tertiary-care hepatology centers in North America to study patients with cirrhosis • NACSELD-III is an IRB-approved registry for outpatients with
Slide 47: alfapump safety profile comparable to standard of care
alfapump safety profile comparable to standard of care Comparison for the six months post-implantation NACSELD-III Registry POSEIDON Pivotal Six month data(1) Matched Patients Cohort(2) Any Death or Hospitalization 55.0% (22/40) 55.0% (22/40) Death 12.5% (5/40) 12.5% (5/40) Hospitalization 42.5% (17
Slide 48: Top 60 liver transplant centers (2021)
Top 60 liver transplant centers (2021) Top 60 centers cover 80% of transplants (6,967 out of 8,685) POSEIDON center (N = 13) Source: Organ Procurement & Transplantation Network, US Dept of HHS (optn.transplant.hrsa.gov) 48 48
Slide 49: Top 61 – 90 liver transplant centers (2021)
Top 61 – 90 liver transplant centers (2021) 30 centers cover 15% of transplants (1,347 out of 8,685) 49 49 Source: Organ Procurement & Transplantation Network, US Dept of HHS (optn.transplant.hrsa.gov)
Slide 50: Leading experts as Heart Failure Scientific Advisors
Leading experts as Heart Failure Scientific Advisors Dr. Maria Rosa Costanzo Dr. Wilson Tang Medical Director of the Edward Center for Professor of Medicine at Cleveland Clinic Lerner Advanced Heart Failure College of Medicine at Case Western Reserve Medical Director Heart Failure Research for the U
Slide 51: Persistent congestion and Worsening renal function
Persistent congestion and Worsening renal function Persistent congestion and worsening renal function are key targets in decompensated heart failure Wattad et al, American Journal of Cardiology, 2015: interaction between worsening renal function and persistent congestion in acute decompensated heart
Slide 52: alfapump DSR - used in RED DESERT & SAHARA
alfapump DSR® - used in RED DESERT & SAHARA Leveraging Sequana Medical’s alfapump – proven implantable pump developed for refractory liver ascites Sodium-free DSR® infusate administered to 1 peritoneal cavity via implanted port 2 Sodium diffuses into DSR infusate 1 alfapump pumps sodium-rich DSR inf
Slide 53: DSR therapy treatment overview
DSR therapy treatment overview DSR Drug Step 1: Peritoneal catheter placement bag Step 2: DSR treatment episode 1. Infusion of DSR Drug 2. 24 hour dwell 3. Drainage DSR • Week 1: 5x DSR therapy Drug • Week 2-4: 3x/week DSR therapy Step 3: Catheter removal DSR Drug + sodium drain bag 53 53
Slide 54: RED DESERT: The first repeated DSR therapy study
RED DESERT: The first repeated DSR therapy study Repeated dose proof-of-concept study of DSR in stable heart failure patients on high dose diuretics alfapump + surgical start DSR therapy discharged from end DSR port implantation in hospital hospital therapy 2 weeks 2 weeks 4 weeks DSR therapy Contin
Slide 55: RED DESERT: Successful proof-of-concept study
RED DESERT: Successful proof-of-concept study 8 euvolemic HF patients on high dose diuretics treated with DSR 3x per week up to 6 weeks Highly effective management of fluid and sodium balance • Generally safe and well tolerated; no clinically relevant hyponatremia Significant improvement in cardio-r
Slide 56: RED DESERT: Highly effective management of fluid & sodium
RED DESERT: Highly effective management of fluid & sodium No loop diuretics required during study despite mean baseline dose of >300 mg/day furosemide equivalents Ejection Fraction (%) NT-proBNP (pg/mL) Daily Dose of loop diuretics (mg)** During DSR Treatment Subject At baseline At baseline At basel
Slide 57: SAHARA: Ph. 2a in target patient population
SAHARA: Ph. 2a in target patient population Decompensated heart failure patients with persistent congestion on high dose diuretics Patient Start DSR Euvolemic End DSR enrolment therapy state therapy Phase 1: Phase 2: Up to 3 x 2 weeks 16 weeks alfapump + port Intensive DSR therapy Maintenance DSR th
Slide 58: SAHARA: Expanding into decompensated patients
SAHARA: Expanding into decompensated patients 10 evaluable diuretic-resistant HF patients with persistent congestion on 2-6 weeks of intensive DSR therapy1 Safely, effectively and rapidly eliminate persistent congestion & restore euvolemia • All patients achieved euvolemia within one week of intensi
Slide 59: Improvement in diuretic response and LD dosing
Improvement in diuretic response and LD dosing Normalization of diuretic-response with dramatic durable reduction in LD needs post-DSR therapy Cumulative 6-hour urine output and urinary sodium excretion following an intravenous 40mg dose of furosemide Oral loop diuretic dose over the first year of f
Slide 60: Significant improvement in volume status
Significant improvement in volume status All SAHARA patients reached euvolemia within seven days of DSR therapy (mean 7kg weight loss) Change in NT-proBNP and Plasma CA125 Change in NT-proBNP for RED DESERT (euvolemic, stable HF) and SAHARA (hypervolemic decompensated HF) Data are presented as Mean
Slide 61: Broad improvement in kidney function
Broad improvement in kidney function Removal of LD for extended period of time results in improved kidney health and function Blood urea nitrogen (BUN) and measured creatinine clearance Cumulative 6-hour uremic toxin excretion - indoxyl sulfate Blue bars indicate data from both RED DESERT and SAHARA
Slide 62: DSR therapy impact on neurohormonal status
DSR therapy impact on neurohormonal status Managing volume status with DSR therapy appear to avoid the neurohormonal activation seen with LDs Urine renin – biomarker of local neurohormonal activation at the level of the kidney Change in plasma renin for RED DESERT (euvolemic, stable HF) and SAHARA (
Slide 63: Improvement in cardiovascular parameters
Improvement in cardiovascular parameters Improvement in LV ejection fraction Change in systolic blood pressure – increase likely rules out any hawthorne impact in study from improvement in medication compliance Blue bars indicate data from both RED DESERT and SAHARA, and red bars indicate data only
Slide 64: Consistently improved NYHA class
Consistently improved NYHA class RED DESERT SAHARA 4IV 4 IV 3 III 3III NYHA Class NYHA Class 2 II 2II 1I 1I 0 0 101-001 101-002 101-003 101-005 101-006 101-007 101-008 01-01 01-03 01-04 01-05 01-06 01-08 01-09 01-10 01-11 01-12 • at screening • post DSR* * Post DSR = end of phase 1 (6w) in RED DESER
Slide 65: Strong reduction in predicted mortality
Strong reduction in predicted mortality Over 75% reduction in predicted one-year mortality based on Seattle Heart Failure Model* • Seattle Heart Failure Model is a highly validated model to predict survival in heart failure • Validated in approx. 10,000 heart failure patients in over 46 countries wi
Slide 66: SAHARA: Safety
SAHARA: Safety No clinically relevant changes in serum sodium levels or progressive hyponatremia • 3 SAEs in 3 patients: • Blocked peritoneal catheter (phase 2) 2 in 2 patients DMC: related to study device but unrelated to implant procedure or treatment DMC: unrelated to study device, • Stable angin
Slide 67: First two US patients successfully treated with DSR 2.0
First two US patients successfully treated with DSR 2.0 MOJAVE non-randomized cohort • At baseline: • Heart failure patients with preserved ejection fraction (HFpEF) and severe diuretic resistance • High dose loop diuretics – furosemide equivalent dose of 1,200 and 800 mg per day • After DSR treatme
Slide 68: Evaluating potential for DSR in renal failure
Evaluating potential for DSR in renal failure Complementary opportunity leveraging heart failure programme capabilities • Like heart failure, kidney failure / dialysis is one of the leading burdens for healthcare systems and carries a high mortality / morbidity burden • Hemodialysis seeks to tackle
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