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May 2025 www.SeaStarMedical.com Nasdaq: ICU Investor Presentation Transforming treatments for critically ill patients facing organ failure and potential loss of life.
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Forward-looking statements This presentation contains certain forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1955. These forward-looking statements include, without limitation, SeaStar Medical’s expectations with respect to the timing of regulatory approval of its products, the expected timing on enrollment, generation of study results, submission of PMA and other corporate milestones, the ability of SCD to treat patients with AKI, and the potential benefits of SCD to treat other diseases. Words such as “believe,” “project,” “expect,” “anticipate,” “estimate,” “intend,” “strategy,” “future,” “opportunity,” “plan,” “may,” “should,” “will,” “would,” “will be,” “will continue,” “will likely result,” and similar expressions are intended to identify such forward- looking statements. Forward-looking statements are predictions, projections and other statements about future events that are based on current expectations and assumptions and, as a result, are subject to significant risks and uncertainties that could cause the actual results to differ materially from the expected results. Most of these factors are outside SeaStar Medical’s control and are difficult to predict. Factors that may cause actual future events to differ materially from the expected results include, but are not limited to: (i) the risk that SeaStar may not be able to obtain regulatory approval of its SCD product candidates; (ii) the risk that SeaStar may not be able to raise sufficient capital to fund its operations, including clinical trials; (iii) the risk that SeaStar Medical and its current and future collaborators are unable to successfully develop and commercialize its products or services, or experience significant delays in doing so, including failure to achieve approval of its products by applicable federal and state regulators, (iv) the risk that SeaStar Medical may never achieve or sustain profitability; (v) the risk that SeaStar Medical may not be able to access funding under existing agreements; (vi) the risk that third-parties suppliers and manufacturers are not able to fully and timely meet their obligations, (vii) the risk of product liability or regulatory lawsuits or proceedings relating to SeaStar Medical’s products and services, (xiii) the risk that SeaStar Medical is unable to secure or protect its intellectual property, and (xi) other risks and uncertainties indicated from time to time in SeaStar Medical’s Annual Report on Form 10-K, including those under the “Risk Factors” section therein and in SeaStar Medical’s other filings with the SEC. The foregoing list of factors is not exhaustive. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and SeaStar Medical assume no obligation and do not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise.
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SEASTAR MEDICAL A commercial-stage healthcare company focused on transforming treatments for critically ill patients facing organ failure and potential loss of life. Changing the standard of care, one patient at a time
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Seasoned, dynamic leadership ERIC SCHLORFF CEO + Board Member TOM MULLEN SVP, Manufacturing and Product Development SAI IYER, PHD SVP, Medical Affairs and Clinical Development DAVID GREEN Chief Financial Officer KEVIN CHUNG, MD Chief Medical Officer TIM VARACEK SVP, Commercial Business Operations 4
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• Achieved 50% enrollment in NEUTRALIZE-AKI pivotal trial • CMS coverage for a portion of trial costs • Adult acute kidney injury population 50x larger than pediatric PIVOTAL TRIAL PROGRESS • Potential application in multiple billion dollar acute and chronic indications • Same SCD, same Mechanism of Action MULTIBILLION- DOLLAR MARKET • Clinically proven to reduce mortality • Health Care Economics shows dramatic reduction in economic burden • Patented, proprietary SCD platform (40 U.S. and 8 foreign issued patents) BEST-IN-CLASS TECHNOLOGY • FDA approval for pediatric acute kidney injury with sepsis in 2024 • QUELIMMUNE (SCD- PED) being used by key children's hospitals • Continuing to expand into additional children’s hospitals • Derisks future FDA approvals COMMERCIALIZING FIRST INDICATION 5 Investment Highlights
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Indication Investigational Feasibility study Pivotal trial Approved QUELIMMUNE: Pediatric acute kidney injury Adult Indications: SCD-ADULT indications require minimal to no device modification for new indications End Stage Renal Disease (ESRD) Hepatorenal syndrome Systemic inflammatory response in cardiac surgery - Adults Systemic inflammatory response in cardiac surgery - Pediatric Robust pipeline with FDA Breakthrough Device Designation to speed potential approval *QUELIMMUNE is approved by the FDA as a Humanitarian Use Device (HUD) to treat pediatric patients with acute kidney injury and sepsis or septic condition weighing 10 kilograms and requiring kidney replacement therapy Approved under a Humanitarian Device Exemption.* Launched in July 2024 Q1’24 Awarded Breakthrough Device Designation by FDA to provide timely access to medical devices by speeding up development, assessment and review for FDA approval. Acute kidney injury Cardiorenal syndrome 6
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Potential approval of the adult AKI indication dramatically increases the market opportunity for our SCD therapy 7 Sources: Estimates of Annual U.S. Patient Population and Total Addressable U.S. Market were derived from Silver SA, Chertow, GM Nephron 2017; 137 (4) 297-301; American College of Physicians, ACP Hospitalist, Coding information from July 2019; Sepanlou, et al. Lancet Gastroenterology & Hepatology, 2020 Mar;5(3):245-266; Orman, et al JAMA Netw Open. 2019 Oct 2;2(10):e1913673. Market sizing in graphic are representative and not to scale. The adult AKI market is estimated to be 50 times the pediatric AKI market. Market opportunities reflect assumptions regarding cartridge pricing and number of cartridges used per patient. AKI = Acute Kidney Injury The total US annual market opportunity for the Adult AKI market is 50 times the size of the Pediatric AKI opportunity. Adult AKI total US annual market ~$4.5B • ~210K total patient market • Pivotal trial underway • Potential approval and launch 2H’26 Pediatric AKI total US annual market is ~ $100M • ~4K total patient market • Launched 3Q’24
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• Pulmonary infiltrates • Lung injury • Acute respiratory distress syndrome • Cardiovascular shock • Disseminated intravascular coagulant • Acute kidney injury End-Organ Damage Innate Immune Response Dysregulated immune response (hyperinflammation) THE PROBLEM: Hyperinflammatory response can lead to multi-organ damage and death Infection / Injury Activated monocytes Activated neutrophils Other inflammatory mediators Cytokines Patient Outcome: Permanent Organ Damage or Death 10
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Neutralization of activated effector cells helps restore homeostasis Cytokine storm Insult or injury Immune response Increased cytokine production from effector cells and the recruitment of additional leukocytes SCD targets the SOURCE of cytokine production The SCD Therapy targets upstream source of effector cells and neutralizes effector cells that release cytokines Other drugs and therapies that focus on individual downstream inflammatory targets such as IL-6, TNF-⍺ etc. fail to address the high redundance in the immune system 11 Neutrophil & Monocyte effector cells SCD-Adult QUELIMMUNE
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Mechanism of action of the SCD therapy • Selectivity of Binding: Neutrophils (70-80%), Monocytes (15-25%), Lymphocytes (0-2%) • Most Activated Neutrophils (CD11b density) and Pro-Inflammatory Monocytes (CD14+) bind to the membranes due to low iCa environment • For Neutrophils: Low iCa environment promotes apoptosis, release from membranes, return to circulation, and clearance by phagocytosis and digestion by bone marrow, liver , and spleen macrophages • For Monocytes: Shift from the most pro-inflammatory circulating phenotype (classical, intermediate) to reparative phenotype (non-classical) Real-time cell processing of circulating neutrophils and monocytes without immunosuppression promotes tissue repair and organ recovery 12
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SCD TECHNOLOGY PLATFORM A potential disease-modifying therapeutic device that neutralizes over-active immune cells and stops the cytokine storm that yields destructive hyperinflammation and creates a cascade of events that wreak havoc in the patient’s body.
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Standard venous return line (renal therapy standard-of- care) Hemofilter Hemofilter to SCD line SCD Venous return line SCD to venous return line Pathway for SCD integration SCD conveniently connects with existing continuous kidney renal therapy that is widely available in U.S. ICUs today Pathway for standard hemofilter Standard of Care Ca2+ replacement Regional citrate anticoagulation Ionized Ca2+ levels: <0.4 mmol/L Unique mechanism of action restores reparative physiology HOMEOSTASIS- RESTORING THERAPY LOWER ionized calcium in circuit with citrate Selectively TARGET highly activated neutrophils & monocytes DEACTIVATE through neutrophil apoptosis and monocyte shift to repair phenotype = 13
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SCD CLINICAL EVIDENCE Clinical data has illustrated the disease modifying potential of SeaStar’s SCD therapy.
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Pediatric patients with acute kidney injury are vulnerable to cytokine storms Despite advances in supportive treatments, pediatric patients with acute kidney injury often deteriorate due to untreated hyperinflammation 27% Overall incidence of acute kidney injury in the pediatric ICU setting1 2x Patients with acute kidney injury stay in the ICU twice as long - 8 days vs 4 days 2 50% For children with acute kidney injury and multi-organ dysfunction requiring continuous kidney replacement therapy 3-5 ≥30% Incidence of chronic kidney disease for pediatric patients with acute kidney injury6 ICU ADMISSIONS LONGER IN ICU MORTALITY CHRONIC DISEASE 15 Kaddourah A, et al. NEJM. 2017; 376:11-20. De Zan F, et al. Blood Purif. 2020;49:1-7. Symons JM, et. al. Clin J. Am Soc Nephrol 2007. Modem V, et al. Crit Care Med 2013. Goldstein, SL, et al. Kidney Int 2005; 67; 653-658. Menon S, et. al Ped Nephr 2023 (38) Suppl 1:S41.
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77% Survival1 At Day 60 Dialysis dependency2 At Day 60 (Post-ICU Discharge) Device-related Immunosuppression, serious adverse events or infections NO NO 1. Goldstein SL, et al. Kidney Medicine. 2024; 6(4);100792. 2. Goldstein SL, et al. Kidney Int Rep. 2020; 6(3):775-84. QUELIMMUNE clinical data in pediatric acute kidney injury * Pooled data from two clinical trials n=22 16 QUELIMMUNE* Standard of Care 50% Activated neutrophil 10% to 30%
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Adult acute kidney injury study outcomes consistent with pediatric studies * Of survivors (Day 60 Post-ICU Discharge) 1. Goldstein SL, et al. Kidney Medicine. 2024; 6(4);100792 2. Tumlin JA, et al. Semin in Dialysis. 2013;26(5):616-23. 3. Tumlin JA, et al. PLoS ONE. 2015; 10(8):e0132482. **Treated per protocol (iCa in therapeutic range using citrate) 4. Uchino S, et al. JAMA. 2005. 5.Bagshaw SM, et al. Crit Care. 2005. 17 87.5% of pediatric patients had normal kidney function at Day 60* 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% % Survival Day 60 Pediatric AKI Adult AKI Adult Historical Control 50% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% % Dialysis Dependence Day 60 No Dialysis Dependence at Day 60 No Dialysis Dependence at Day 60 25% Pediatric AKI Adult AKI n=16 n=35n=6 n=22 n=19 n=16 n=35n=6 n=22 n=19 Adult Historical Control Survival at Day 60 Dialysis Dependence at Day 60
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Safety Profile of SCD therapy across 6 adult & pediatric AKI studies • No device-related infections, immunosuppression or SAEs across >150 patients • >50% of these patients were septic Study # (Descriptor) # SCD Treated Patients # SCD Used per Patient (mean) Total # SCD Used Total SCD Exposure Time (hours) # AEs # SAEs # Device-Related SAEs # Device-Related Infections O-USA Pilot Study 9 3.9 34 816 14 0 0 0 ARF-002 Pilot Study 35 4.3 150 3,508 199 28 0 0 SCD-003 69 5.2 359 8,611 354 80 0 0 SCD-PED-01 16 5 80 1,936 47 12 0 0 SCD-PED-02 6 4.6 28 660 29 6 0 0 SCD-0051 22 8.2 181 4,344 70 50 0 0 TOTALS 157 5.3 832 19,875 713 176 0 0 1 8 In SCD-005, all but 1 patient had AKI. 1. Humes HD, et al. Crit Care Explor. 2023 Oct 19;5(10):e0995. OUS = outside U.S.
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COMMERCIAL OPPORTUNITY PEDIATRICS
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Commercial strategy for pediatric acute kidney injury targeting top 50 leading children’s hospitals 1. https://www.childrenshospitals.org. 2. America Hospital Directory Database Export January 2020 3. https://www.beckershospitalreview.com/lists-and-statistics/30-largest-childrens-hospitals-in-the-united- states.html 20 First product shipped in July 2024 Initial Launch: Top 5 U.S. Pediatric Children's Hospitals Key elements of our commercial strategy: • Focus on top sites to drive cost efficiencies • Target early adopters: ~20% of top 50 hospitals have prior experience with QUELIMMUNE • Decouple device use through Human Device Exemption and requirement for Patient Registry participation to enable critical care use when patient presents at the hospital • Deploy skilled nursing and other experts to sites to ensure smooth transition to adoption of QUELIMMUNE • Manage all aspects of the sales and distribution process to reduce middleman fees and ensure prompt delivery of product 220 U.S. Children’s Hospitals Treat ~4,000 pediatric AKI patients 50 hospitals treat 50% of AKI patients
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QUELIMMUNE provides value to a hospital’s bottom line
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ADVANCING THE PIPELINE ADULT AKI
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Mortality rates for critically ill patients with AKI requiring Renal Replacement Therapy in ICU setting2-5 1. Silver SA, & Chertow GM, Nephron 2017. 2. Uchino S, et al. JAMA 2005. 3. Mehta RL, et al Kidney Int 2004. 4. Modem V, et al. Crit Care Med 2013. 5. Goldstein SL, et al. Kidney Int 2005. 6. Coca SG, et al. Kidney Int 2012. 7. 2022 USRDS Annual Report; accessed 20Aug2023. Each year in the US1: Increased hospitalization costs: As high as $24 billion >200,000 adult cases of AKI 50%+ 8X More likely to develop end- stage renal disease following severe AKI episode6 $100K Cost of a single patient for one year of dialysis7 22 High unmet need in adult AKI Newsweek article sites AKI as post-operative risk in cardiac surgeryClick here to read more Newsweek article sites AKI as post - operative risk in cardiac surgery Click here to read more
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Adult acute kidney injury pivotal trial design • Adults aged 18-80 in ICU with acute kidney injury > stage 2 requiring CRRT > 12 h < 48 hours • One additional life-threatening organ dysfunction • Commitment to maintain current level of care for > 96 hours • C-reactive Protein > 3.5 mg/dL Patient Population Assess the safety & efficacy of SCD in acute kidney injury patients requiring continuous renal replacement therapy (CRRT) Trial Objective 23 CRRT Control SCD Therapy + CRRT Patients need to be on CRRT for ≥ and meet I/E criteria
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NEUTRALIZE-AKI pivotal trial gaining momentum • 100 of up to 200 subjects enrolled (50% to date) • 16 medical sites activated • Mix of academic, military and community hospitals • CMS reimbursement for Medicare/Medicaid patients (reduces trial costs, increases site activations and accelerates enrollment) • Interim data review of first 100 subjects at 90-days post-treatment • Final analysis following last 90-day endpoint • Present results at scientific conferences • Publish results in peer-reviewed medical journal • PMA filing in 2026 24 University of Alabama University of Cincinnati Methodist Hospital Metropolitan University of Iowa Hospital
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SCD platform - Approach to clinical development: Scientifically Driven, Cost-Effective, Medical-Community Focused 26 SCD PLATFORM Presentations at scientific meetings Publish manuscripts Research grants (non - dilutive financing) University of Michigan research Scientific Advisory Board Case studies and compassionate use requests Chaired by David Humes, MD, SCD inventor, Professor, Division of Nephrology - University of Michigan 11 world-renowned leaders in pediatric and adult nephrology, critical care and translational science Engage and Drive the Science Publications and Presentations
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28 Capital structure As of May 14, 2025 Ticker Symbol Price* Shares Outstanding Market Capitalization* Warrants Outstanding Weighted Average Exercise Price for Warrants Interest-bearing Debt ICU $1.27* 10,621,285 $13.5 6,480,300 $32.80 $291,085 *At market close 5/13/25
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2024 2025 2026 QUELIMMUNE commercial product launch Breakthrough Device Designation for additional indications Initiate feasibility trial in cardiorenal syndrome QUELIMMUNE launch expansion: up to 20 hospital systems $3.6 million NIH grant for severe cardiorenal syndrome Topline data severe cardiorenal syndrome U.S. commercial launch for adult AKI FDA approval for adult AKI (50x more patients than pediatric) Catalysts to drive value creation QUELIMMUNE FDA approval for pediatric acute kidney injury SCD-ADULT QUELIMMUNE CMS coverage for adult acute kidney injury trial costs 30 Topline data from pivotal adult acute kidney injury trial Breakthrough Device Designation for additional indications Awarded FDA Breakthrough Designation for Chronic Dialysis
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• Achieved 50% enrollment in NEUTRALIZE-AKI pivotal trial • Adult acute kidney injury population 50x larger than pediatric • CMS coverage for a portion of trial costs PIVOTAL TRIAL PROGRESS • Potential application in multiple billion dollar acute and chronic indications • Same SCD, same Mechanism of Action MULTIBILLION- DOLLAR MARKET • Clinically proven to reduce mortality • Health Care Economics shows dramatic reduction in economic burden • Patented, proprietary SCD platform (40 U.S. and foreign issued patents) BEST-IN-CLASS TECHNOLOGY • FDA approval for pediatric acute kidney injury with sepsis in 2024 • QUELIMMUNE (SCD- PED) being used by key children's hospitals • Continuing to expand into additional children’s hospitals • Derisks future FDA approvals COMMERCIALIZING FIRST INDICATION 28 Investment Highlights Investor Contact: IR@SEASTARMED.COM
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May 2025 www.SeaStarMedical.com Nasdaq: ICU Investor Presentation Bringing organ-restoring solutions to critically ill patients Investor Contact: IR@SEASTARMED.COM