Sequana Medical N.V · EURONEXT:SEQUA
Sequana Medical — Investor Presentation (December 2023)
67 slides from Sequana Medical's investor presentation, December 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 – December 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: Targeting large markets with strong growth
Targeting large markets with strong growth Tackling significant unmet medical need in liver disease and heart failure alfapump – treating recurrent & DSR – novel treatment for cardiorenal refractory ascites due to liver cirrhosis syndrome in heart failure • Successful North American pivotal study –
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: Q4 ‘23: Heart failure H
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 strong 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 Asc
Slide 7: Clear limitations of existing treatment options
Clear limitations of existing treatment options Little innovation or new development SoC: Paracentesis (“drainage”) Painful, burdensome, short term benefit, QoL impact Permanent Catheter System “Normal Life” External Catheter, Risk for Infections / Blockage Decreased mobility & Drainage or appetite,
Slide 8: alfapump – continuous ascites removal to the bladder
alfapump – continuous ascites removal to the bladder Fully implanted automatic device for long term treatment 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 throu
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 target market / year ~$500MM in 2025: 12+ paracentesis 78,000 / year patients with >$2.5 Bn recurrent or 6-7% CAGR refractor
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 at 12 months post-implant
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: Strong clinical messaging to patients and clinicians
Strong clinical messaging to patients and clinicians 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 go
Slide 13: Attractive pricing with derisked reimbursement
Attractive pricing with derisked reimbursement Existing DRG payment and breakthrough device designation de-risk reimbursement Coding – Strong existing position with potential for further upside • Existing US hospital DRG payment for alfapump procedure of $60-70K in target hospitals* • Supports alfap
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 Clear need for new options to tackle congestion for sufficient time without the problems of loop diuretics • Combined, and self-reinforcing dysfunction of heart and kidneys with hypothesised complex and interconnected mechanisms • Clinical profile
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 key driver
DSR (Direct Sodium Removal) targets key driver 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 removed fr
Slide 19: Breaking the CRS vicious cycle improves outcomes
Breaking the CRS vicious cycle improves outcomes Rapid and effective decongestion PLUS improvement in cardio-renal status Clinical proof-of-concept from RED DESERT and SAHARA studies Complete replacement of loop diuretics with safe, rapid and effective decongestion and maintenance of euvolemia Nor
Slide 20: 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 21: Very strong data from three non-randomised patients
Very strong data from three non-randomised patients Data from first randomised cohort planned for H2 ’24; top-line data expected H2 ’25 for partnering • Safe and effective maintenance of euvolemia without the need for loop diuretics • Considerable benefit in cardiorenal health • Dramatic improvement
Slide 22: 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 23: Outlook
Outlook Strong near term value drivers with clear long term potential
Slide 24: 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: Q4 ‘23: Heart failure H
Slide 25: Contact info
Contact info IR@sequanamedical.com +32 498 053579 www.sequanamedical.com
Slide 26: Back-up
sequanamedical
Slide 27: 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 27 27
Slide 28: 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 29: 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 30: 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 31: 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 32: POSEIDON: Primary effectiveness endpoints exceed 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 33: 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. 33
Slide 34: 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 ii
Slide 35: 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 36: POSEIDON: Comparable number of serious infections
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 37: 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 38: 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 39: QoL: Maintaining clinically meaningful improvement
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 39 39
Slide 40: SF-36 Physical Component Score predicts 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 41: 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 42: 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 43: 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 44: Data support alfapump as 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 45: 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 46: 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 47: 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) 47 47
Slide 48: 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) 48 48 Source: Organ Procurement & Transplantation Network, US Dept of HHS (optn.transplant.hrsa.gov)
Slide 49: RED DESERT: First repeated DSR therapy study
RED DESERT: First repeated DSR therapy study Repeated dose proof-of-concept study of DSR in euvolemic heart failure patients on high dose diuretics start DSR therapy discharged from end DSR in hospital hospital therapy 2 weeks 4 weeks DSR therapy Continued DSR therapy (in-patient) (out-patient) Diur
Slide 50: RED DESERT: 8 euvolemic heart failure patients
RED DESERT: 8 euvolemic heart failure patients Severely ill heart failure patients on high doses of oral loop diuretics N=8 Ejection Fraction – % 24 ± 3 (Mean ± SD) NT-proBNP – pg/mL* 4,589 ± 2,945 (Mean ± SD) Furosemide equivalents – mg/day 323 ± 263 (Mean ± SD) Serum creatinine - µmol/L 120 ± 53 (
Slide 51: 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 52: SAHARA: Expansion into decompensated HF patients
SAHARA: Expansion into decompensated HF patients Decompensated heart failure patients with persistent congestion on high dose diuretics Start DSR® Euvolemic End DSR therapy state therapy Phase 1: Phase 2: Up to 3 x 2 weeks 16 weeks Intensive DSR therapy Maintenance DSR therapy “Recompensate / Decong
Slide 53: SAHARA: 10 heart failure patients with persistent congestion
SAHARA: 10 heart failure patients with persistent congestion N=10 Ejection Fraction – % 23 ± 4 (Mean ± SD) NT-proBNP – pg/mL* 6,628 ± 2,483 (Mean ± SD) Furosemide equivalents – mg/day 360 ± 197 (Mean ± SD) Serum creatinine - µmol/L 142 ± 46 (Mean ± SD) eGFR – mL/min/1.73m2 51 ± 23 (Mean ± SD) NT-pro
Slide 54: SAHARA: Successful proof-of-concept study
SAHARA: Successful proof-of-concept study 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 intensive D
Slide 55: Long-term improvement in cardio-renal health
Long-term improvement in cardio-renal health Durable and dramatic reduction in oral loop diuretic dosing as a result of improved disease status 600 ~23 months follow-up mg furosemide equivalents 500 RED DESERT 400 101-001 101-002 300 101-003 200 101-005 101-006 100 101-007 0 101-008† 800 700 ~15 mon
Slide 56: 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 57: 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 58: 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 59: 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 60: 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 61: 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 62: 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 63: MOJAVE: Positive results from non-randomized cohort
MOJAVE: Positive results from non-randomized cohort US heart failure patients (N=3) with preserved ejection fraction (HFpEF) and severe diuretic resistance** • All three US patients successfully treated with DSR 2.0 • Maintenance of euvolemia without the need for any loop diuretics • No clinically r
Slide 64: 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 65: DSR Delivery – Low risk innovation drives convenience
DSR Delivery – Low risk innovation drives convenience 4-week DSR therapy with decreasing frequency / ~30 minutes at doctor’s office or infusion center TODAY NEXT FUTURE VISION PD catheter Subcutaneous Port Port and Pump Fill - doctor’s office Fill Fill + attach pump - infusion center - doctor’s offi
Slide 66: 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
Slide 67: 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
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