SeaStar Medical : Investor Presentation March

NASDAQ: ICU seastarmedical.com

Innovative Solutions for the

Consequences of a Dysregulated

Immune Response

Investor Presentation

March 2024

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, including the equity line of credit and forward purchase 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.

1. 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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About SeaStar Medical

We are advancing an innovative platform therapy to address the life- threatening consequences of a dysregulated immune response

The overproduction of inflammatory cells (i.e., cytokine storm) can damage vital organs, resulting in multi-organ failure & death

Our Selective Cytopheretic Device (SCD) cell-directed extracorporeal therapy can bring activated cells back to a reparative state & homeostasis

SCD quells the dysregulated immune process & cytokine storm by targeting & neutralizing activated effector cells

1st FDA approval granted in February 2024

QuelimmuneTM Product Family

SCD-PED

SCD-ADULT

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Investment Highlights

• Proprietary technology with demonstrated significant benefit against potentially life- threatening unmet medical need
• SCD-PEDapproved under Humanitarian Device Exemption (HDE) in pediatric acute kidney injury (AKI) due to sepsis or septic condition, providing validation for technology platform
• Activating sites & enrolling patients in the pivotal NEUTRALIZE-AKI trial addressing a significantly larger adult AKI patient population & market size
• Generating clinical data that demonstrates potential significant economic value of technology
• Technology has potential applications in multiple acute & chronic high-value indications using adult SCD with minimal to no modifications
• World-classteam focused on executing our business strategy & achieving goal of improving patient outcomes & saving lives

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Pediatric SCD-PED Approved Under HDE

• Approval order received in February 2024
• • Pediatric patients >10 kg (~22 lbs) with AKI due to sepsis or septic condition in ICU with kidney replacement therapy (KRT)
  • Validates technology approach of SCD as a therapeutic device in addressing dysregulated immune response
  • Met HDE guidelines - probable benefit in treatment of condition that affects < 8,000 U.S. patients each year
  • 1st product approval in Quelimmune product family
• Clinical data bolstered by submission to FDA of written statements and testimonials from:
• • Clinicians with experience using SCD-PED to improve clinical outcomes in pediatric patients
  • Parents of children with AKI in ICU who attest to SCD-PED's role in child's recovery
  • National professional society of pediatric nephrologists urging FDA to ensure device is rapidly

made available to the pediatric community

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Dysregulated Immune Response: Serious Condition Can Lead to Permanent Organ Damage & Death

Hyperinflammation /

Cytokine Storm

Key Drivers

BacterialViral

InfectionInfection

TraumaSurgery

Condition that Develops when Immune System

Responds too Aggressively to Injury or Infection

End-Organ Damage & Failure

	•	Pulmonary infiltrates
	•	Lung injury
	• Acute respiratory distress syndrome
Can Lead To
	(ARDS)
	•	Cardiovascular shock
	•	Disseminated intravascular coagulant
	•	Renal failure (AKI)

Permanent Organ Damage or Death

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SCD Modulates Immune Effector Cells Responsible for a Dysregulated Immune Response

	Innate immune
	response
Activated	Activated
monocytes	neutrophils

	Innate immune
	response
Activated	Activated
monocytes	neutrophils

SCD*

Effector cell

References:

1. Chen J, et al. Front Pharmacol. 2021.
2. Karki R, et al. J Transl Med. 2022.
3. Kumar V. Intl Immunopharmacol. 2020.
4. Chang Y, et al. Int J Mol Sci. 2022.
5. Kellum JA, et al. Nat Rev Dis Primers. 2021.
6. Yessayan LT, et al. Crit Care Expl. 2022.

Other inflammatory

Cytokinesmediators

Dysregulated immune response / hyperinflammation

Ultimately leading to…

ORGAN DAMAGE or DEATH

deactivation and modulation

Deactivated	Deactivated
monocytes	neutrophils
Cytokines	Other inflammatory
	mediators
	Dysregulated
	immune response /
	hyperinflammation

IMPROVED CLINICAL

OUTCOMES

*SCD is currently under investigation and has not been approved. There is no guarantee that the product will receive authority approval and become commercially available for the uses being investigated.	7

Convenient Integration in ICU at Point of Patient Care

Continuous Kidney Replacement Therapy
						SCD to venous
		Venous return line			return line
Ca2+
Replacement			(disconnected from
		Standard
				CCRT Hemofilter)
		venous return line
		(SOC for Renal			Ionized Ca2+
		Replacement
				SCD levels:
		Therapy)
				0.25 - < 0.4 mmol/L
	Regional	Citrate
		(disconnected
	Anticoagulation		from CKRT
					Hemofilter)

Hemofilter

Hemofilter to SCD line

Pathway for standard hemofilter

LOWER ionized calcium in circuit with citrate

Selectively TARGET highly activated neutrophils & monocytes

DEACTIVATE through neutrophil apoptosis and monocyte shift to repair phenotype

=

HOMEOSTASIS-

RESTORING THERAPY

CKRT: continuous kidney replacement therapy; SOC: standard of care	8

What Types of Patients Have Been Treated with the SCD?

3 Organ	50%-60%
Failure	Sepsis
On average	Among patients

SCD-PED

SCD-ADULT

Acute Kidney Injury (AKI) on CKRT

Comorbidities Include (but not limited to):

• BMI over 40 (morbidly obese)
• COVID-19
• All in ICU

Insults Include (but not limited to):

• Surgery
• Trauma
• Bacterial & Viral Infections

Underlying Etiologies Treated:

• CRS
• HLH
• HRS
• STEC-HUS
• STSS

AKI: acute kidney injury; BMI: body mass index; CRS: cardio-renal syndrome; HLH: hemophagocytic lymphohistiocysosis; HRS: hepato-renal syndrome; STEC-HUS:Shiga-toxin E. coli hemolytic uremic	9
syndrome; STSS: Streptococcal toxic shock syndrome

Significantly Reduced Mortality & Elimination of Dialysis Dependency Demonstrated Across Multiple AKI Clinical Studies

			Mortality Rate		Dialysis Dependency
				(60 Days)		(60 Days)
Non-COVID	Patients	Mortality		SCD	Control	SCD	Control
AKI Studies	Treated	Reduction
OUS Study	9	56%		22%	78%1	0%	25%
U.S. Adult Pilot 002	35	19%		31%	50%3	0%	25%
U.S. Adult ARF 003	19/272	25%		16%	41%	0%	25%
U.S. Peds SCD-PED-01	16	25%		25%	50%3	0%	15%-25%
(≥ 20 kg wt)
U.S. Peds SCD-PED-024	6	33%		17%	50%3	0%	TBD
(≥10 to ≤20 kg wt)

1. Case matched controls based on SOFA Scores and age 2. Treated per protocol (iCa in therapeutic range using citrate) 3. Historical control based on published studies 4. SCD PED-02 interim results were reported at the ASN Kidney Week 2022 Annual Meeting, Abstract TH-PO039.

ARF: Acute Renal Failure	10