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Item 1. Business

2025-03-27 compared with 2024-04-16 · 308 added, 255 removed, 449 unchanged (56% of the section changed)

Unless the context otherwise requires, all references in this section to "SeaStar Medical," the “Company,” “we,” “us” or “our” refer to SeaStar Medical Holding Corporation and its consolidated subsidiaries following the Business Combination (as defined herein), other than certain historical information that refers to the business of SeaStar Medical, Inc.

Unless the context otherwise requires, all references in this section to “SeaStar Medical”, the “Company”, “we” “us” or “our” refer to SeaStar Medical Holding Corporation and our consolidated subsidiaries following the Business Combination (as defined herein), other than certain historical information that refers to the business of SeaStar Medical, Inc.

(the “Predecessor”) prior to the consummation of the Business Combination.

We are a clinical stage medical technology company developing a proprietary platform therapy, our Selective Cytopheretic Device (“SCD”), to reduce the consequences of hyperinflammation on vital organs.

The inflammatory response is critical to fend off infections and repair damaged tissue in the body.

Central to inflammation are the cells within blood and lymph circulatory systems, called white blood cells (primarily neutrophils and monocytes), also referred to commonly as “pus” cells.

We are a commercial-stage healthcare company focused on transforming treatments for critically ill patients facing organ failure and potential loss of life.

Our Selective Cytopheretic Device (“SCD”) is designed as a disease-modifying 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.

It has broad potential applications for patients suffering from both acute and chronic kidney disease as well as cardiovascular and other serious inflammatory diseases.

We received Food and Drug Administration (“FDA”) approval on February 21, 2024, under a Humanitarian Device Exemption (“HDE”) for our pediatric SCD therapy.

It is the only FDA approved product for use in pediatric patients with acute kidney injury (“AKI”) due to sepsis or a septic condition requiring kidney replacement therapy.

We shipped our first commercial pediatric SCD (“QUELIMMUNE”) in July 2024.

In addition, we are currently conducting a pivotal clinical trial to assess the safety and efficacy of the SCD therapy in critically ill adult patients with AKI requiring continuous renal replacement therapy (“CRRT”).

Our SCD therapy has been awarded Breakthrough Device Designation (“BDD”) for four therapeutic indications by the FDA, including the use of the SCD therapy for adult patients with AKI, patients with cardiorenal syndrome awaiting left ventricular assist device (“LVAD”) implantation, patients with hepatorenal syndrome, and patients with end stage renal disease (“ESRD”).

The BDD enables the potential for a speedier pathway to approval and the ability to have more frequent and flexible meetings with FDA.

The inflammatory response is essential to the healing process of critical organs;

however, the overactivation of inflammatory cells, which can be triggered by many different bodily insults such as trauma, surgery or infection, can send the body into shock and cause severe damage to a variety of critical organs such as the heart, lungs and kidney.

Central to inflammation are the cells within blood and lymph circulatory systems, called white blood cells (primarily neutrophils and monocytes).

In a normal inflammatory response, neutrophils are the first immune cells to arrive at the site and are key to the entire immune response that kills pathogens and promotes tissue repair.

These inflammatory cells release chemicals (cytokines) that trigger the immune system to eliminate the foreign pathogens or damaged tissue, enhancing the immune response.

If the inflammatory response becomes excessive and dysregulated (referred as proinflammatory), normal neutrophil cells die off (“apoptosis”), allowing the inflammatory cells to continue to produce cytokines, further enhancing the dysregulated immune response, and altering feedback mechanisms that regulate the immune system.

This results in damaging hyperinflammation spreading uncontrollably to other parts of the body, often leading to acute chronic solid organ dysfunction or failure, including heart, lung, kidney and liver diseases.

These inflammatory cells release chemicals (cytokines) that trigger the immune system to eliminate foreign pathogens or damaged tissue, enhancing the immune response.

If the inflammatory response becomes excessive and dysregulated (referred to as proinflammatory), the inflammatory cells will continue to produce cytokines and other damaging molecules, further enhancing the dysregulated immune response, and altering feedback mechanisms that regulate the immune system.

This results in damaging hyperinflammation spreading uncontrollably to other parts of the body, often leading to acute chronic solid organ dysfunction or failure, including the heart, lung, kidney, liver, and even death.

This hyperinflammatory response is also known as the “cytokine storm,” referring to the body’s reaction to the category of small-secreted proteins released by hyperinflammatory cells that affect communication between cells.

The cytokine storm, when left uncontrolled, can lead to organ damage and even death.

Based on clinical and preclinical studies conducted over the last 15 years, the Company’s technology has shown promise in modulating the degree of activity of proinflammatory cells to help reduce tissue damage and speed the repair and recovery of organ function.

We believe this approach, if successful, will transform the ability of clinicians to treat acute organ failure in the intensive care unit (“ICU”) and to improve organ function in hospitalized patients.

Currently, few therapeutics are available to clinicians to address hyperinflammation and for those options that do exist, such options are either immunosuppressive or only target one cytokine.

Currently, there are no therapeutic options that specifically neutralize the white blood cells that are primarily responsible for the destructive hyperinflammatory response.

Clinicians typically address hyperinflammation with therapies that are either immunosuppressive or that target one cytokine, both of which are generally suboptimal in the treatment of hyperinflammation.

We believe our technology has the potential to overcome limitations in existing anti-inflammatory treatments and address the challenge of selectively targeting activated neutrophils and monocytes.

We are leveraging our patent protected and scalable SCD technology platform to develop proprietary therapies that are organ agnostic and target both acute and chronic indications.

Preclinically, our SCD was tested in various animal models, which include acute myocardial infarction, intracranial hemorrhage, chronic heart failure, sepsis, and acute respiratory distress syndrome.

The animal models demonstrated the inflammatory response and how it was modified by our SCD.

We will continue to explore the application of our SCD technology across a broad range of markets and indications where proinflammatory activated neutrophils and monocytes may contribute to disease progression or severity in both acute and chronic indications.

We are using our SCD initially to clinically validate several acute organ injury indications, including kidneys and lungs.

Our investigational SCD is an extracorporeal synthetic membrane device designed to be easily integrated into existing continuous renal replacement therapy ("CRRT") systems that are commonly installed in hospitals, including in ICUs throughout the United States.

Once approved and commercialized, our SCD would initially target acute kidney injury in both the pediatric CRRT population as well as adults on CRRT.

In addition, we are developing our SCD to address inflammation associated with chronic dialysis and chronic heart failure.

There is substantial clinical demand for safe and effective control of hyperinflammation.

The use of our SCD to reverse the cytokine storm in pediatric and adult patients with acute kidney injury on CRRT in clinical studies with more than 140 patients reduced mortality rates by 50%, and, of those patients who survive 60 days, none have required dialysis.

In June 2022, we submitted a humanitarian device exemption ("HDE") application with the U.S.

Food & Drug Administration ("FDA") for pediatric patients with acute kidney injury ("AKI") on CRRT.

On February 22, 2024, we received the FDA HDE Approval Order, which allows sales to qualified healthcare facilities.

We intend to continue to shape our commercial and distribution strategy by expanding indications and pursue collaborations with partners in markets where such partners provide strategic capabilities in commercializing our product candidates and enabling access to specific patient populations.

On December 27, 2022, we entered into a license and distribution agreement (the “Distribution Agreement”) with Nuwellis, Inc.

(“Nuwellis”), pursuant to which we appointed Nuwellis as our exclusive distributor for the sale and distribution of our pediatric SCD product throughout the United States once we receive from the FDA a written authorization to market such product for pediatric use pursuant to our HDE application.

Pursuant to the Distribution Agreement, we received an upfront payment , and will receive milestone payments upon achievement of certain milestones and royalties on gross sales of the SCD product.

The Distribution Agreement has an initial term commencing on December 27, 2022 and shall end on the three (3) year anniversary from the date that is the earlier of (a) ninety (90) days after we receive FDA authorization to market such SCD product for pediatric use and (b) the first commercial sale of the SCD product.

The term of the Distribution Agreement may be automatically extended for additional terms of one (1) year and for a total of two (2) consecutive extensions.

Each party has the right to terminate the Distribution Agreement for material breach if such breach is not cured within ninety (90) days after written notice and we have additional rights to terminate the Distribution Agreement in accordance with other terms set forth in the Distribution Agreement.

On December 29, 2023, the Distribution Agreement was amended and the Distributor shall pay Supplier the following milestone payments set forth below on the later to occur of (i) 30 days after achievement of the corresponding milestone events or April 1, 2024, and the Distributor has waived the repayment of the upfront payment from Supplier.

In addition, on February 9, 2023, we received approval from the FDA of our investigational device exemption ("IDE") application to conduct a pivotal study evaluating the effectiveness of SCD in reducing hyperinflammation in adults with AKI requiring CRRT.

The Company began enrollment in Q2 2023 and expect to generate interim study results during the second half of 2024 and topline study results and submission of a Pre-market Approval ("PMA") application in the first half of 2025.

There is no guarantee that we will complete the AKI adult trial in a timely manner, or at all, nor will there be any assurance that positive data will be generated from such trial.

Even if we are able to generate positive results from these trials, the FDA may require us to conduct additional trials to support the study, or disagree with the design of the trials and request changes or improvements to such design.

We have received two additional Breakthrough Device Designations ("BDD") in 2023, totaling three.

On April 29, 2022, we received a Breakthrough Device Designation ("BDD") for the use of our SCD in the treatment of immunomodulatory dysregulation in adult patients (18 and older) with AKI, which is expected to accelerate the regulatory approval process for such trial.

On September 28, 2023, we received Breakthrough Device Designation for our patented and cell-directed SCD for use with patients in the hospital ICU with acute or chronic systolic heart failure and worsening renal function due to cardiorenal syndrome or right ventricular dysfunction awaiting implantation of a left ventricular assist device.

On October 18, 2023, we received Breakthrough Device Designation for our patented and cell-directed SCD for use with patients in the hospital ICU with AKI and acute on chronic liver failure.

We have been granted three

Breakthrough Device Designations from the FDA for the SCD device, each of which is expected to expedite the clinical development and regulatory review of the SCD for use in the designated patient population.

We believe that our novel therapeutic device is readily applicable for use in other indications, which will require additional clinical studies and FDA approval and increase the addressable market for our SCD technology.

As we continue our work to expand indications, we believe we will have the ability to take advantage of economies of scale to reduce costs of production.

We believe our scalable manufacturing process demonstrates a significant competitive advantage in the hyperinflammatory market.

We have pursued patent protection for our SCD technology as well as other technologies.

Clinical and preclinical studies conducted over the last 15 years have demonstrated that our SCD therapy can modulate the degree of activity of proinflammatory cells to help reduce tissue damage and speed the repair and recovery of organ function.

Data from our trials demonstrated that the use of our SCD therapy to reverse the cytokine storm in more than 150

pediatric and adult patients with acute kidney injury on CRRT reduced mortality rates by 50%, and of those patients who survived 60 days, none have required dialysis.

We believe our SCD therapy has the potential to transform the treatment of acute organ failure in the intensive care unit (“ICU”) and to improve organ function in patients with chronic kidney disease, certain cardiovascular diseases, and other serious inflammatory diseases.

Preclinically, we evaluated our SCD therapy in various animal models representing multiple hyperinflammatory indications, including acute myocardial infarction, intracranial hemorrhage, chronic heart failure, sepsis, and acute respiratory distress syndrome.

The animal models demonstrated the inflammatory response and how it was modified by our SCD therapy.

We will continue to explore the application of our SCD therapy across a broad range of indications where proinflammatory activated neutrophils and monocytes contribute to disease progression or severity in both acute and chronic indications.

We are leveraging our patent protected and scalable SCD therapy platform to develop proprietary treatments that are organ agnostic and target both acute and chronic indications.

The SCD therapy is delivered via an extracorporeal synthetic membrane device that easily integrates into existing CRRT systems that are commonly employed for patients with acute organ injury in hospitals, including in ICUs throughout the United States.

It also has the potential to be integrated into kidney dialysis systems for chronic kidney disease patients receiving renal replacement therapy at centers throughout the United States.

We believe that the ease of use and broad applicability of the therapy across multiple disease states should enable us to capture a sizable market for our SCD therapy with increasingly favorable economics.

Our senior management team and Board have an average of over 19 years of experience in the healthcare industry, including expertise in regulatory and medical affairs, commercialization and distribution in our initial therapeutic priority areas.

We also have assembled a team of well-respected scientific advisors who are experts in the development of our technology and products.

There is a substantial clinical need for safe and effective control of hyperinflammation and we believe that our first-in-class SCD therapy can address the large potential market of over one million patients each year that face life-threatening hyperinflammatory conditions, including organ failure and potential loss of life.

SCD Therapy for Pediatric Patients

We are currently commercializing our first product, QUELIMMUNE, under an HDE that was approved by the FDA on February 21, 2024.

QUELIMMUNE is currently the only FDA approved product for critically ill pediatric patients with life-threatening acute kidney injury (AKI) due to sepsis or a septic condition.

We commenced our first product shipment of QUELIMMUNE in July 2024 and are now targeting top-tier pediatric medical facilities for adoption of the QUELIMMUNE therapy.

As a condition of the approval, the FDA stipulated that we would need to institute a post approval patient surveillance registry to track certain safety and performance metrics.

This typically requires an Internal Review Board (“IRB”) review and approval to use QUELIMMUNE therapy at the medical facility, which can lengthen the QUELIMMUNE adoption process.

To date, we have 5 active commercial sites that have completed the registry process and have purchased and used QUELIMMUNE therapy.

Additional site activations are planned for 2025.

SCD Therapy for Adult Patients

We are currently conducting a pivotal trial, NEUTRALIZE-AKI, to evaluate the safety and efficacy of our SCD therapy in 200 adults with AKI in the ICU receiving CRRT.

The trial’s primary endpoint is a composite of 90-day mortality or dialysis dependency of patients treated with SCD therapy in addition to CRRT as the standard of care, compared with the control group receiving only CRRT standard of care.

The trial protocol includes an interim analysis by an independent Data Safety Monitoring Board (“DSMB”) at the trial’s 90-day primary endpoint with the first 100 subjects.

As of March 25, 2025, we had enrolled 94 patients in the pivotal trial.

We anticipate reporting topline clinical trial results and the submission of a Pre-market Approval ("PMA") application in 2026.

We are also evaluating additional clinical development of the SCD therapy in adults based on unmet clinical needs and market opportunity.

Our BDD awards by the FDA in four therapeutic areas are expected to expedite the clinical development

and regulatory review of the SCD therapy for use in the designated patient populations and are the primary focus of our future clinical development decisions.

We received our first BDD in 2022, two additional BDDs in 2023, and a fourth BDD in 2024.

• On April 29, 2022, we received a BDD for the use of our SCD in the treatment of immunomodulatory dysregulation in adult patients (18 and older) with AKI, which is expected to accelerate the regulatory approval process for our ongoing pivotal trial.

• On September 28, 2023, we received BDD for our SCD for use in patients in the hospital ICU with acute or chronic systolic heart failure and worsening renal function due to cardiorenal syndrome or right ventricular dysfunction awaiting implantation of a left ventricular assist device.

• On October 18, 2023, we received BDD designation for our SCD for use with patients in the hospital ICU with AKI and acute on chronic liver failure.

• On November 6, 2024, we received BDD for our SCD to treat chronic systemic inflammation in end-stage renal disease (ESRD) patients who require chronic hemodialysis, also known as chronic dialysis.

This is our first BDD in a chronic disease setting.

We believe that our SCD therapy is readily applicable for use in other indications, which will increase the addressable market for our SCD therapy, but will also require additional clinical studies and FDA approval.

We have pursued patent protection for our SCD therapy as well as other technologies.

Our patent portfolio consists of 34 patents and 7 pending patent applications in the U.S.

and certain foreign jurisdictions.

Of these patents and patent applications 33 are owned exclusively by us, and 15 are co-owned with the University of Michigan ("UOM").

UOM has granted to us an exclusive worldwide, royalty bearing license to UOM’s interest in all of the co-owned patents and applications.

This license permits the Company to commercialize our SCD in all human therapeutic indications.

Of these patents and patent applications 20 patents and 4 patent applications are owned exclusively by us, and 14 patents and 3 patent applications are co-owned with the University of Michigan (“UOM”).

The UOM has granted to us an exclusive worldwide, royalty bearing license to the UOM’s interest in all of the co-owned patents and applications.

This license permits us to commercialize our SCD therapy in all human therapeutic indications.

For more information, see “Intellectual Property” below.

Our senior management team and Board have an average of more than 19 years of experience in the healthcare industry, including expertise in medical affairs, commercialization and distribution in our initial therapeutic priority areas.

We are also supported by a group of well-respected scientific advisors who are experts in the development of our technology and products.

The acute inflammatory response occurs in a well-defined coordinated sequential response.

Our Approach - The SCD Therapeutic Device

Our SCD therapy is designed as a disease-modifying 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.

In many serious acute illnesses, a hyperinflammatory response occurs as a well-defined coordinated sequential response.

Neutrophils are the first responders followed by monocytes.

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The first are proinflammatory macrophages, followed by patrolling, reparative macrophages.

This complex tightly coordinated process is critical for host defense and tissue repair but needs to be tightly regulated by the body’s inflammatory signaling and cellular apoptosis.

If not, further tissue destruction may occur when uncontrolled hyperinflammation leads to degradative reparative processes with worsening tissue or organ function.

This complex highly coordinated process is critical for host defense and tissue repair but needs to be tightly regulated by the body’s inflammatory signaling and cellular apoptosis.

If it is not tightly regulated and begins to spiral out of control, further tissue destruction may occur when uncontrolled hyperinflammation leads to degradative reparative processes with worsening tissue or organ function.

If this excessive systemic inflammation is severe and prolonged, multi-organ failure, including cardiovascular, respiratory, kidney, liver and neurologic dysfunction may occur, resulting in poor clinical outcomes.

Prior therapeutic approaches to block soluble mediator targets, such as a cytokines or free radicals have not proven successful.

Prior therapeutic approaches to block soluble mediator targets, such as cytokines or free radicals have not proven successful.

We believe that our SCD approach, which targets activated cells, is a potentially transformative, if not disruptive, therapeutic approach to a range of acute and chronic inflammatory disorders.

Our SCD is an extracorporeal synthetic membrane device designed to bind activated leukocytes (neutrophils and monocytes) as part of a CRRT extracorporeal circuit.

When added to the circuit and release of a standard CRRT system (using regional citrate anticoagulation) immediately following a standard hemofilter cartridge, blood within

the standard hemofilter cartridge enters our SCD and disperses among the fibers of the device.

Our SCD therapy is an extracorporeal synthetic membrane device designed to bind activated leukocytes (neutrophils and monocytes) when integrated into an existing CRRT circuit in conjunction with the use of regional citrate anticoagulation (“RCA”).

The SCD is simply added to the standard CRRT circuit that uses regional citrate anticoagulation and is placed immediately following the standard hemofilter cartridge.

Highly inflamed blood from the patient passes through the CRRT system and hemofilter and into the SCD.

In the low calcium environment mediated by RCA, the inflamed cells in the blood are

modulated towards a less inflammatory state.

Upon exiting our SCD under a low calcium environment, the blood is returned to the patient’s body.

Our SCD delivers its therapeutic benefit by attenuating the excessive inflammatory response of activated neutrophils and monocytes.

Uninterrupted, the excessive inflammatory response progresses to multi-organ failure (“MOF”), with documented increases in both morbidity and mortality in critically ill patients.

Our initial lead product is focused on critically ill AKI pediatric and adult patients on CRRT.

Our SCD leverages the existing footprint of CRRT pump systems in ICUs today, as well as the growing use and adoption of regional citrate as an anticoagulant.

Our SCD therapy delivers its therapeutic benefit by attenuating the excessive inflammatory response of activated neutrophils and monocytes.

Uninterrupted, the excessive inflammatory response progresses to multi-organ failure, with documented increases in both morbidity and mortality in critically ill patients.

Our initial approved product, QUELIMMUNE, is focused on critically ill AKI pediatric patients on CRRT.

Our SCD therapy leverages the existing footprint of CRRT pump systems in ICUs today, as well as the growing use and adoption of regional citrate as an anticoagulant.

Citrate is used to bind the free ionized calcium within the extracorporeal circuit which is needed to impact the neutrophils and monocytes.

A recent study in the Journal of the American Medical Association in 2020 demonstrated that while the use of regional citrate anticoagulation has the same mortality profile as heparin, regional citrate anticoagulation now showed to be more effective in preserving filter life as used to create the low calcium environment for our SCD, which impacts the white cells interaction with the SCD membrane leading to the reduction in inflammation.

A recent study in the Journal of the American Medical Association in 2020 demonstrated that while the use of regional citrate anticoagulation has the same mortality profile as heparin, regional citrate anticoagulation has been shown to be more effective in preserving filter life and is used to create the low calcium environment for our SCD therapy, which impacts the white cells interaction with the SCD membrane leading to the reduction in inflammation.

Mechanism of Action

The mechanism of action of our SCD consists of two steps:

1) binding activated neutrophils and monocytes on our SCD biomimetic membrane and 2) deactivating the activated neutrophils by maintaining a specified ionized calcium level within our SCD.

Our SCD utilizes clinically approved regional citrate anticoagulation protocols to lower the ionized calcium level, which prevents blood clogging within the circuit and immuno-modulates the activated

neutrophils, which are then returned to the patient.

The mechanism of action of our SCD therapy consists of three elements:

(i) selectively binding activated neutrophils and monocytes on our SCD biomimetic membrane (ii) deactivating the activated neutrophils by maintaining a specified ionized calcium level within our SCD, and (iii) shifting proinflammatory monocytes to a lower inflammatory profile.

Our SCD utilizes clinically validated regional citrate anticoagulation protocols to lower the ionized calcium level, which not only prevents clotting within the circuit but also immuno-modulates the activated neutrophils and monocytes, which are then returned to the patient.

Calcium is then infused into the blood returning to the patient from the SCD, thereby maintaining normal calcium levels in the patient throughout the process.

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In the case of neutrophils, calcium can have a profound effect on their activity.

It has been shown that lowering calcium levels in neutrophils can lead to higher levels of neutrophil apoptosis (deactivation).

Our SCD is designed to selectively bind the most highly activated neutrophils (associated with hyperinflammation) and in a low iCa environment, the activated neutrophils are deactivated, which has the effect of reducing hyperinflammation.

It has been shown that lowering calcium to critical levels in the regional circuit can lead to higher levels of neutrophil apoptosis (deactivation).

Our SCD is designed to selectively bind the most highly activated neutrophils, associated with hyperinflammation, and in a low ionized calcium (“iCa”) environment, the activated neutrophils are deactivated, which has the downstream effect of reducing hyperinflammation.

These deactivated cells are then released back into circulation, resulting in no downstream immunodepletion or immunosuppression.

When neutrophils are in homeostasis, the normal half-life is six to eight hours, but in a hyperinflammatory state, neutrophil apoptosis is delayed, leading to increased numbers of activated neutrophils in circulation.

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We believe the role of circulating monocytes in systemic inflammation and organ-specific injury is becoming more appreciated by healthcare professionals.

Calcium also has an important influence on monocyte activity.

A high percentage of the circulating monocyte subtypes (M1 proinflammatory versus M2 patrolling, reparative) has been shown to influence the degree of acute organ injury and chronic organ dysfunction.

In vitro, our SCD membranes in a low iCa perfusion circuit binds the proinflammatory monocytes within the blood more selectively.

This selective binding has been shown in clinical trials and results in less proinflammatory circulating monocytes in inflammatory disorders.

Similar to calcium’s effect on neutrophils, calcium also has an important influence on monocyte activity.

A high percentage of the circulating monocyte-derived macrophage subtypes (M1 proinflammatory versus M2 patrolling, reparative) have been shown to influence the degree of acute organ injury and chronic organ dysfunction.

In in vitro testing, we have shown that, in a low iCa environment, our SCD membrane binds the proinflammatory monocytes within the blood more selectively and lowers their inflammatory activity.

This selective binding and immunomodulation has also been shown in human clinical trials and results in fewer proinflammatory circulating monocytes.

It is important to note that our SCD does not sequester 100% of these monocytes as they are important to maintaining immune homeostasis.

Similar to neutrophils above, immunomodulated monocytes are also released back into circulation following treatment, resulting in no downstream immunodepletion or immunosuppression.

We call the SCD mechanistic process of binding these cells, deactivating them, and releasing them back into circulation as “catch-and-release” system.

Histological evaluation of our SCD

Microscopy of our SCD after being used for patient treatment demonstrated the binding of leukocytes on the outer surface of the membranes of the cartridge along the blood flow path within the extracorporeal circuit.

The bound leukocytes were dominated by neutrophils and monocytes (see Figure 1 below).

The ability of neutrophils and monocytes to bind to the outer walls of the hollow fiber membranes (figure below) rather than the inner walls, which is the conventional blood flow path, is due to the difference in shear forces of blood flow.

The sheer force of our SCD is similar to capillary flow providing a microenvironment for the neutrophils and monocytes, enabling the cells to catch and release.

Microscopy of our SCD after being used for patient treatment demonstrated the binding of leukocytes on the outer surface of the hollow fiber membranes of the cartridge along the blood flow path within the extracorporeal circuit.

Flow cytometry confirmed that they were the most activated neutrophils and monocytes (see Figure 1 below).

Activated leukoctyes adherence to the membranes.

Light micrograph stained with Hematoxylin and Eosin (H&E).

Low-power micrograph showing adherent cells around each fiber (160x).

Panel B and C:

Higher-power micrographs showing the clustering of bound leukocytes (400x).

High-power micrograph displaying predominance of neutrophils and monocytes in the adherent cell clusters (1600x)

The unique blood path within the SCD mimics capillary flow, providing a more stable microenvironment for the neutrophils and monocytes, enabling the cells to bind to the outer surface of the hollow fibers long enough for the critically low iCa to have its impact.

This is then followed by cells being released back into the circulation.

– “catch and release”).

Our Market Opportunity

We are a therapeutic medical device company.

Our clinical data was used to support an HDE submission to the FDA to request approval to market our SCD to hospitals and clinicians with pediatric patients suffering from AKI.

Our clinical data has also been used to support the initiation of a pivotal PMA study in adult AKI.

In the long term, we intend to pursue the application of our SCD technology to additional indications, including acute respiratory distress syndrome, chronic dialysis, cardiorenal syndrome and hepatorenal syndrome and others.

We are a therapeutic medical device company pursuing multiple large market indications with our SCD .

Our clinical data was initially used to support an HDE submission to the FDA to request approval to market our SCD to hospitals and clinicians with pediatric patients suffering from AKI.

Our clinical data has also been used to support the initiation of a pivotal PMA study in adult AKI which has an estimated 210,000 patients annually in the United States.

In the long term, based on preliminary clinical evidence, we intend to expand the application of our SCD technology to additional indications with large patient populations, including acute respiratory distress syndrome, chronic dialysis, cardiorenal syndrome and hepatorenal syndrome and others.

Our Initial Market Opportunity in Acute Kidney Injury

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Kidneys also refrain from revealing the impact to the rest of body and organs (and vice-versa) and often are not considered systemically for co-treatment.

Globally consistent criteria for diagnosing AKI have recently emerged with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease ("RIFLE"), an international consensus classification for AKI staging and diagnosing guidelines introduced in 2004, the Acute Kidney Injury Network ("AKIN") staging system in 2007, and finally the Kidney Disease:

Globally consistent criteria for diagnosing AKI have recently emerged with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease, an international consensus classification for AKI staging and diagnosing guidelines introduced in 2004, the Acute Kidney Injury Network staging system in 2007, and finally the Kidney Disease:

Improving Global Outcomes, AKI Staging and Diagnosing Guidelines published in 2012.

These sources have helped clinicians to both improve recognition, staging, diagnosing and subsequent documentation of less obvious cases of AKI secondary diagnoses.

These sources have helped clinicians to improve recognition, staging,

diagnosing and subsequent documentation of less obvious cases of AKI secondary diagnoses.

While our initial market is focused on AKI patients on CRRT, future indications will likely benefit from improved characterization and diagnosis of patients.

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and Baxter International, which represent over 80% of the market today in the U.S.

Since 2010, a significant amount of data has been published to quantify the clinical and financial impact of AKI, resulting in a broadening AKI treatment “boom” beyond dialysis to areas of diagnostics, complimentary therapies, and pharmacologics.

As hospital administrators and government officials gain understanding of the impact and burden of AKI increases, we believe that attention will continue to grow.

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The pediatric population for AKI patients in the U.S.

is estimated to be less than 8,000 patients per year, which is a substantially small sub-set of the 6 million AKI patient population.

on CRRT is estimated to be less than 8,000 patients per year, which is a substantially small sub-set of the 6 million AKI patient population.

The AKI market needs new and effective solutions, and hospitals continue to search for and evaluate new products.

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• Execute on clinical plan through key relationships:

Our initial focus on the treatment of AKI in adults and pediatrics is supported by our long and established relationship with UOM, which licenses to us certain key technology underpinning our novel immunomodulatory therapy, as well as other leading academic hospitals and institutions throughout the U.S.

Our initial focus on the treatment of AKI in adults and pediatrics is supported by our long and established relationship with the UOM, which licenses to us certain key technology underpinning our novel immunomodulatory therapy, as well as other leading academic hospitals and institutions throughout the U.S.

Such relationships enable us to expand and refine the design and execution of our clinical plans with a more targeted outcome and objectives.

In addition, we have submitted the HDE for the pediatric AKI indication in June 2022.

On February 21, 2024, we received the FDA HDE Approval Order, which allows sales to qualified healthcare facilities.

In February 2023, the Company received FDA IDE approval for the adult AKI indication.

In February 2023, we received FDA IDE approval for the adult AKI indication.

This indication has received the FDA BDD for our SCD therapy targeting AKI adult patients, is expected to accelerate and streamline the regulatory approval process prior to the commercial launch of our product candidates.

On October 18, 2023, we received Breakthrough Device Designation for our patented and cell-directed SCD for use with patients in the hospital ICU with AKI and acute on chronic liver failure.

We have been granted three Breakthrough Device Designations from the FDA for the SCD device, each of which is expected to expedite the clinical development and regulatory review of the SCD for use in the designated patient population.

On October 18, 2023, we received a BDD for our patented and cell-directed SCD for use with patients in the hospital ICU with AKI and acute on chronic liver failure.

On November 6, 2024, we received Breakthrough Device Designation for our patented and cell-directed SCD to treat chronic systemic inflammation in end-stage renal disease (ESRD) patients who require chronic hemodialysis, also known as chronic dialysis.

We have been granted four Breakthrough Device Designations from the FDA for the SCD device, each of which is expected to expedite the clinical development and regulatory review of the SCD for use in the designated patient population.

• Differentiation through medical education:

We intend to dedicate resources to educate physicians, hospital clinicians and other decision makers in the medical communities on the role of neutrophils and monocytes in both acute and chronic indications, and therapeutic benefit of controlling and modulating excessive inflammatory response.

We intend to dedicate resources to educate physicians, hospital clinicians and other decision makers in the medical communities on the role of neutrophils and monocytes in both

acute and chronic indications, and therapeutic benefit of controlling and modulating excessive inflammatory response.

We intend to focus our marketing strategies not only on the therapeutic capabilities of our technology, but also the economic consequences of hyper-inflammation in the current standard of care and treatment infrastructure and highlight the differentiating factors of our SCD product candidates that can provide a cost-effective solution.

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• Scaling production with manufacturing partners:

As we progress through our planned clinical trials and anticipate the potential commercial launch of our SCD product candidates if FDA approval is received, we are focused on identifying and securing various suppliers and manufacturing partners to scale production in response to the expected demand for our solutions.

We continue to negotiate with suppliers of raw materials, including filters, tubing and other components, to establish redundancies and alternative sources to mitigate interruptions in the supply chain in the future.

As we progress through our planned clinical trials and the commercial launch of our SCD in pediatrics (QUELIMMUNE) as well as additional adult product candidates if FDA approval is received, we are focused on identifying and securing various suppliers and manufacturing partners to scale production in response to the expected demand for our solutions.

We continue to negotiate with suppliers of raw materials, including cartridges, tubing and other components, to establish redundancies and alternative sources to mitigate interruptions in the supply chain in the future.

In addition, we may also explore strategic relationships with partners who can provide sources of raw materials while collaborating with us on the marketing and distribution of our product candidates.

Our Clinical Stage Product Candidates

Our Commercial Stage Product

The following disclosure summarizes the key clinical studies in which our SCD product candidates (QUELIMMUNE for pediatrics) have been evaluated.

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We obtained an Approvable Letter for the HDE in October 2023.

On February 23, 2024, we announced a final Approval Order for the HDE.

On February 23, 2024, we announced a final Approval Order for the HDE, which allows us to commercialize QUELIMMUNE.

As of the date of this report, we have five commercial customers and several potential customers evaluating QUELIMMUNE.

Clinical Progression

SCD 006 Pivotal Study (“SCD 006”) Design

We are actively enrolling and treating patients in a pivotal clinical trial of the SCD for the treatment of AKI in adults under a granted Breakthrough Device Designation (BDD) (April 2022) by the FDA.

This trial ("SCD-006";

NCT05758077) is a 200 subject, prospective, multi-center, open label, randomized, two-arm comparative pivotal study conducted in the United States.

We are actively enrolling and treating patients in a pivotal clinical trial of the SCD for the treatment of AKI in adults under a granted BDD (April 2022) by the FDA.

This trial (NCT05758077) is a 200 subject, prospective, multi-center, open-label, randomized, two-arm comparative pivotal study conducted in the United States.

SCD-006 is designed to assess a composite endpoint of both mortality or dialysis dependency at Day 90 (see schematic figure below).

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Current Trial Status

As of March 25, 2025, we have enrolled 94 patients into our SCD-006 pivotal trial.

We submitted the SCD-006 IDE Protocol to the FDA on January 6, 2023, and attained approval in March 2023.

We began enrollment in the second quarter of 2023, and we anticipate the enrollment period to last 24 to 28 months.

On April 29, 2022, we received a BDD for the use of our SCD in the treatment of immunomodulatory dysregulation in adult patients (18 and older) with AKI, which is expected to aide our discussions related to the regulatory review and approval process for SCD-006.

We currently anticipate generating interim results from this trial in late 2024 and topline study results and submission of a PMA application by early 2026.

On April 29, 2022, we received a BDD for the use of our SCD in the treatment of immunomodulatory dysregulation in adult patients (18 and older) with AKI, which is expected to aid our discussions related to the regulatory review and approval process for SCD-006.

We currently anticipate generating interim results from this trial in the middle of the 2025 calendar year and topline study results and submission of a PMA application in the middle of the 2026 calendar year.

Additional clinical studies under IDEs include cardiorenal syndrome and hepatorenal syndrome.

We are also conducting exploratory clinical research at the University of Michigan to define the patient population for potential treatment with SCD product candidates, and any future studies will be based upon initial clinical data collected in these studies.

We are also conducting exploratory clinical research with the University of Michigan to define the patient population for potential treatment with SCD product candidates, and any future studies will be based upon initial clinical data collected in these studies.

Other Clinical Studies

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SCD-003 was a controlled, randomized, and multicenter clinical trial that was initiated in September 2011 and terminated in September 2013 under an FDA approved IDE.

For this trial, the control group received standard CRRT with RCA and the SCD-treated group received up to seven days of SCD therapy.

For this trial, the control group received standard CRRT with regional citrate

anticoagulation (“RCA”) and the SCD-treated group received up to seven days of SCD therapy.

The study was sponsored by the Predecessor with the support of a third-party contract research organization.

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Furthermore, none of the SAEs were considered ‘definitely’ device related per the principal investigator.

The amount of time patients in both the control and treatment group were maintained in the recommended iCal range (0.23 - 0.40 mmol/L), as specified in the study protocol, was substantially lower than expected.

Of the 134 patients enrolled in the SCD-003 protocol at the time of the interim analysis, 19 SCD patients

(CRRT + SCD) and 31 control patients (CRRT alone) were maintained in the protocol’s recommended range for greater or equal to 90% of the therapy time.

The amount of time patients in both the control and treatment groups were maintained in the recommended iCal range (0.23 - 0.40 mmol/L), as specified in the study protocol, was substantially lower than expected.

Of the 134 patients enrolled in the SCD-003 protocol at the time of the interim analysis, 19 SCD patients (CRRT + SCD) and 31 control patients (CRRT alone) were maintained in the protocol’s recommended range for greater or equal to 90% of the therapy time.

The study was subsequently terminated.

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The primary objective of the study was to evaluate the safety of up to seven consecutive 24-hour treatments of our SCD.

The secondary objective was to evaluate the efficacy of up to seven consecutive 24-hour SCD treatments on all-cause mortality and dialysis dependency at Day 28 and Day 60.

The secondary objective was to evaluate the efficacy of up to seven consecutive 24-hour SCD treatments on all-cause mortality and dialysis

dependency at Day 28 and Day 60.

This study was sponsored by the Predecessor with the support of a third-party contract research organization.

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This data was published in the journal Kidney Medicine in February 2024.

Chronic Applications in Inflammatory Disorders and Corresponding Studies at the University of Michigan (“UoM”)

Chronic Applications in Inflammatory Disorders and Corresponding Studies at the UOM

We are evaluating the safety and efficacy of our SCD in preliminary clinical trials that may lead to applications for our SCD in additional patient populations.

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The SCD therapy was evaluated in a cohort of 15 end-stage renal disease (ESRD) patients on chronic hemodialysis.

The therapy promoted a shift in monocytes from a predominantly proinflammatory to a reparative phenotype.

The therapy promoted a shift in monocytes from a predominantly proinflammatory to a reparative anti-inflammatory phenotype for up to two weeks.

Adverse events or serious adverse events (SAEs) were minimal during SCD treatment and RCA, with four of the 13 patients experiencing adverse events.

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this condition is increasing in incidence with an estimated one million hospital admissions annually in the United States.

Once hospitalized, these patients are treated with a high dose of

intravenous diuretics to relieve persistent congestion.

Once hospitalized, these patients are treated with a high dose of intravenous diuretics to relieve persistent congestion.

The use of diuretics, however, frequently results in worsening renal function, progression of heart failure and death.

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Based on this data, our SCD recently received BDD for CRS in October 2023.

These results were recently published in the journal PLoS One in April 2023 and an additional perspective article was published in the journal European Journal of Heart Failure in February 2024.

These results were recently published in

the journal PLoS One in April 2023 and an additional perspective article was published in the journal European Journal of Heart Failure in February 2024.

Hepatorenal Syndrome (HRS)

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The primary outcome is expected to measure the change in regional wall abnormalities identified on an echocardiogram.

Initial results are expected to provide important feasibility data for a

follow-on study to undertake a controlled randomized clinical trial to evaluate the clinical efficacy of our SCD in myocardial stunning hemodialysis patients.

We source critical components from vendors that have been approved and qualified through our vendor management program.

Fresenius Medical Care North America (“FMCNA”) is the current supplier of the filter used in our pediatric acute kidney injury indication.

Initial results are expected to provide important feasibility data for a follow-on study to undertake a controlled randomized clinical trial to evaluate the clinical efficacy of our SCD in myocardial stunning hemodialysis patients.

We procure conventional components such as tubing sets, clamps, fittings, and labels from various suppliers.

These components are then used in our assembly of SCD clinical kits.

Critical components are procured from suppliers that have been approved and qualified through our supplier management program.

Fresenius Medical Care North America (“FMCNA”) is the current supplier of the cartridges used in our SCD.

In March 2022, we entered into a supply agreement (the “Supply Agreement”) with an FMCNA affiliate, Fresenius USA Marketing, Inc.

(“FUSA”), to supply certain filters at an agreed amount per case for use in our SCD product in our upcoming clinical trial and any additional clinical trials.

We may resell the filters as part of the SCD system in both an Emergency Use Authorization application as well as a future PMA-approved product.

The initial term of the Supply Agreement is for three years commencing on March 31, 2022.

(“FUSA”), to supply certain cartridges at an agreed amount per case for use in our SCD product, including in our upcoming clinical trial and any additional clinical trials.

We may resell the cartridges as part of the SCD system under our HDE approval, pursuant to an Emergency Use Authorization application as well as a future PMA-approved product.

Either party may terminate the Supply Agreement for uncured material breach or for the insolvency of the other party.

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We have agreed to indemnify FUSA against certain third-party claims.

We are in the process of developing a second source for the adult and pediatric filters, which will enable us to better manage any supply disruptions.

In addition, we have secured a supplier to provide the tubing set required to assemble the SCD device, although we are able to identify and secure additional sources of supplies for the tubing set as it is readily available in the market.

The Supply Agreement contains a provision granting FUSA a right of first refusal for the first three years after regulatory approval of our SCD product candidate to distribute the pediatric and adult products in the United States.

If during such period, SeaStar Medical elects to promote and sell the SCD through distributors, SeaStar Medical will be required to provide FUSA with a right of first refusal to be SeaStar Medical’s exclusive distributor of the SCD in the United States and its territories, provided that the SCD is not promoted or sold in a manner that is incompatible with any devices manufactured and/or sold by FUSA or its affiliates.

In December 2024, we entered into the Second Amendment to the initial Supply Agreement, which extended the Supply Agreement through December 31, 2027, updated a part number as well as clarified that FMCNA has 90 days to provide notice to us in the event that FUSA intends to switch the fibers within the SCD as well as the first right of refusal to be the exclusive distributor of the SCD in the United States.

In addition to the Supply Agreement with FUSA, we are developing a second source for both adult and pediatric cartridges, which will enable us to better manage potential supply disruptions.

Additionally, use of the SCD in hospital settings requires the administration of RCA and calcium replacement into CRRT circuitry for safe and effective use.

Both components are intravenous (“IV”) solutions, which are commonly stocked by hospital systems.

However, there are limited manufacturers/suppliers of these IV solutions nationwide, and any supply chain disruptions may have detrimental effects to the utilization of CRRT, and subsequently, use of commercial QUELIMMUNE or the adult SCD in clinical studies.

The Supply Agreement contains a provision granting FUSA a right of first refusal for the first three years after regulatory approval of our SCD product candidate to distribute QUELIMMUNE and adult SCD products in the United States.

If during such period, we elect to promote and sell the SCD through distributors, we will be required to provide FUSA with a right of first refusal to be our exclusive distributor of the SCD in the United States and its territories, provided that the SCD is not promoted or sold in a manner that is incompatible with any devices manufactured and/or sold by FUSA or its affiliates.

On December 27, 2022, we entered into a license and distribution agreement with Nuwellis.

We appointed Nuwellis as our exclusive distributor for the sale and distribution of SCD product throughout the United States once we receive written authorization from the FDA to market our SCD for pediatric use pursuant to our HDE application.

In May 2024, we provided notice to Nuwellis that Nuwellis had breached the Distribution Agreement and that the Distribution Agreement would terminate effective August 18, 2024.

Nuwellis disputed the validity of the termination and on October 20, 2024, we entered into the Settlement Agreement with Nuwellis, pursuant to which we agreed to pay Nuwellis an aggregate of $900,000 payable in three installments through December 31, 2024.

As of December 31, 2024, we fulfilled all of our obligations to Nuwellis and have hired sales and marketing employees focused on the commercialization of QUELIMMUNE into the U.S.

Third-Party Reimbursement

We anticipate that coverage and reimbursement by Centers for Medicare and Medicaid Services ("CMS") and private payors will be essential for most patients and health care providers to pay for our treatments, particularly in the applications of continuous renal replacement therapy for dialysis access and the treatment of hyperinflammatory conditions, including AKI.

We anticipate that coverage and reimbursement by Centers for Medicare and Medicaid Services CMS and private payors will be necessary for most adult patients and health care providers to pay for our treatments, particularly in the applications of continuous renal replacement therapy for dialysis access and the treatment of hyperinflammatory conditions, including AKI.

Accordingly, future sales of our products will depend substantially, both domestically and abroad, on reimbursement by government authorities, private health coverage insurers and other third-party payors.

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It is difficult to predict what CMS will decide with respect to coverage and reimbursement for fundamentally novel products.

See “ Risk Factors — Risks Related to the Company’s Business Operations — Should the Company’s

products be approved for commercialization, lack of third-party coverage and reimbursement for the Company’s devices could delay or limit their adoption .”

See “ Risk Factors — Risks Related to Our Business Operations — Should our products be approved for commercialization, lack of third-party coverage and reimbursement for our devices could delay or limit their adoption .”

Intellectual Property

We currently have multiple U.S.

and foreign patents and patent applications that protect our proprietary technologies.

We strive to protect the proprietary technologies that we believe are important to our business.

We have and will continue to seek patent protection for our SCD product and related technologies, as well for any future products.

In addition to seeking patent protection, we also rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.

In addition to seeking patent protection, we also rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider

appropriate for, patent protection.

We also rely on know-how, confidentiality agreements, license agreements and other agreements to establish and protect our proprietary rights.

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Patent and Trademark Office in granting a patent.

patent term may be shortened, if a patent is terminally disclaimed by its owner, over another patent.

The Company currently has 18 issued U.S.

The term of a U.S.

patent may be shortened, if a patent is terminally disclaimed by its owner, over another patent.

We currently have 16 issued U.S.

patents and 4 pending U.S.

patent applications.

The Company also has 22 issued foreign patents and has 3 pending foreign patent applications.

The Company’s issued patents begin to expire in 2028, with the last of these patents expiring in 2034, although terminal disclaimers, patent term extension or patent term adjustment can shorten or lengthen the patent term.

We also have 18 issued foreign patents and 3 pending foreign patent applications.

We have issued patents that have terms expiring from 2025 through 2034, although terminal disclaimers, patent term extension or patent term adjustment can shorten or lengthen the patent term.

The following table summarizes the number of our patents and patent applications as of December 31, 2024:

Foreign Patents

Foreign Applications

SCD Technology (Patent Families 1-5)

Other Technology (Patent Families 6-9)

With respect to our SCD technologies, we own patents and patent applications in five patent families.

The patents and applications in Patent Family 1 are co-owned by the Company and UOM.

The patents and applications in Patent Families 2-5 are solely owned by the Company.

With respect to our SCD technologies, we own patents and patent applications in four patent families.

The patents and applications in Patent Family 1 are co-owned by us and the UOM.

The patents and applications in Patent Families 2-4 are solely owned by us.

The inventions disclosed in Patent Families 1-4 were developed with U.S.

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These patents will expire from 2028-2031, and the pending application, if granted, will expire in 2028, assuming that the required maintenance fees are paid.

We also co-own with UOM counterpart patents granted in Canada, Japan and New Zealand.

These counterpart patents will expire in 2028, assuming that the required maintenance fees are paid.

We also co-own with the UOM counterpart patents granted in Canada, Japan and New Zealand, and pending applications in Europe and Hong Kong.

These counterpart patents, and pending applications, if granted, will expire in 2028, assuming that the required maintenance fees are paid.

The patents and applications in Patent Family 1 are as follows:

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United States

Methods for treating subject with sepsis

Methods for treating subjects with sepsis

United States

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Systems for treating leukocytes and platelets and methods for treating subject having inflammatory conditions by processing leukocytes or platelets

Systems and methods for processing leukocytes and

platelets and systems for treating inflammatory conditions

Systems and methods for processing leukocytes and platelets and systems for treating inflammatory conditions

A device for processing activated leukocytes and platelets

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Systems and methods for processing leukocytes and platelets and for treating inflammatory conditions

A device that processes platelets or leukocytes

A device for treating an inflamatory condition

* Expiration date if application is granted.

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federal government funding and is subject to obligations under the Bayh-Dole Act.

Pursuant to a license agreement with UOM (as amended, the “UOM License Agreement”), UOM has granted us a worldwide, royalty bearing, exclusive license to their interest in the co-owned patents and applications in Patent Family 1 in the field of medical devices for human therapeutics for certain technologies used in the SCD technology platform, including composition of matter and methods of use patents.

In consideration for such exclusive license, during the term of the UOM License Agreement, we agreed to pay UOM a royalty fee equal to 1% of net sales and reimbursement of patent costs.

To date, we have not paid and do not owe any royalty payments under the UOM License Agreement.

We have paid approximately $124 thousand in patent costs reimbursement since January 1, 2020.

Pursuant to a license agreement with the UOM (as amended and restated, the “UOM License Agreement”), UOM has granted us a worldwide, royalty bearing, exclusive license to their interest in the co-owned patents and applications in Patent Family 1 in the field of medical devices for use in human therapeutics for certain technologies used in the SCD technology platform, including composition of matter and methods of use patents.

In consideration for such exclusive license, during the term of the UOM License Agreement, we agreed to pay the UOM a royalty fee equal to 1% of net sales as well as a one-time milestone payment of $0.1 million upon FDA approval of the first licensed product under the license, and to reimburse patent costs.

As of December 31, 2024, we have incurred less than $5 thousand in royalties owed from sales of the Pediatric SCD.

Since January 2020, we have paid approximately $0.1 million to the UOM to reimburse patent costs under the license.

The UOM License Agreement also imposes certain diligence obligations on us and requires us to achieve specified milestone events by a certain date.

Under the UOM License Agreement, UOM’s liability is limited and we agreed to indemnify and hold UOM harmless in connection with the use of the licensed technology and activities related to the products created using such licensed patents and/or technology.

The UOM License Agreement will remain in effect, unless earlier terminated, until all licensed patents have expired.

If we materially breach the terms of the UOM License Agreement, UOM has a right to terminate the

In some cases, we may have an opportunity to cure a material breach within 30 days or 90 days, but in some cases UOM may terminate the agreement immediately upon our breach.

We may also terminate the agreement by giving UOM 90-day advanced notice provided certain conditions are met.

In addition to the co-owned patents and patent applications in Family 1, we also solely own four additional patent families (Families 2-5) directed to the SCD technology.

Patent Family 2 includes one U.S.

patent and one pending U.S.

Under the UOM License Agreement, the UOM’s liability is limited and we agreed to indemnify and hold the UOM harmless in connection with the use of the licensed technology and activities related to the products created using such licensed patents and/or technology.

In October 2024, the parties amended the agreement to eliminate the 10% of any milestone payments, fees, etc.

in exchange for extending the 1% royalty on net sales until the later of (a) expiration of the last to expire of the patent rights or (b) the ten (10) year anniversary of the first commercial sale, unless sooner terminated as provided in another specific article of this agreement.

The UOM License Agreement will remain in effect until the later of the expiration of all licensed patents or the ten-year anniversary of the first commercial sale under the agreement, unless terminated early.

If we materially breach the terms of the UOM License Agreement, the UOM has a right to terminate the agreement.

In some cases, we may have an opportunity to cure a material breach within 30 days or 90 days, but in some cases the UOM may terminate the agreement immediately upon our breach.

We may also terminate the agreement by giving the UOM 90-day advance notice provided certain conditions are met.

In addition to the co-owned patents and patent applications in Family 1, we also solely own three additional patent families (Families 2-4) directed to the SCD Technology.

Patent Family 2 includes two U.S.

patents, and one pending U.S.

patent application directed to a second generation of the SCD cartridge and methods for using our SCD cartridge to process leukocytes.

The patent will expire in 2031, and the application, if granted, will expire in 2031, assuming that the required maintenance fees are paid.

Counterpart patents have been granted in Australia, Europe, and Japan with the European patent having been validated in France, Germany, Italy, Spain, and the United Kingdom, and a patent application is pending in Canada.

These patents, and the application, if granted, will expire in 2031, assuming that the required maintenance fees are paid.

The patents will expire in 2032, and the application, if granted, will expire in 2031, assuming that the required maintenance fees are paid.

Counterpart patents have been granted in Australia, Canada, Europe, and Japan with the European patent having been validated in France, Germany, Italy, Spain, and the United Kingdom.

These patents will expire in 2031, assuming that the required maintenance fees are paid.

The patents and the application in Patent Family 2 are as follows:

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Methods for processing leukocytes or platelets and for treating a subject with an inflammatory condition

United States

Methods for processing leukocytes or platelets and for treating a subject with an inflammatory condition

Cartridge for treating leukocytes or platelets and methods for treating a subject with an inflammatory condition

France, Germany,

Italy, Spain, & UK

France, Germany, Italy, Spain and the United Kingdom

Cartridge for sequestering leukocytes or platelets

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These patents will expire in 2032, assuming that the required maintenance fees are paid.

Counterpart patents have been granted in Australia, and patent applications are pending in Canada and Europe.

These patents, and patent applications, if granted, will expire in 2032, assuming that the required maintenance fees are paid.

Counterpart patents have been granted in Australia and Canada, and a patent application is pending in Europe.

These patents, and patent application, if granted, will expire in 2032, assuming that the required maintenance fees are paid.

The patents and applications in Patent Family 4 are as follows:

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federal government funding and is subject to obligations under the Bayh-Dole Act.

Patent Family 5 includes three U.S.

design patents, three European Community design patents, and three United Kingdom design patents directed to a medical device connector as follows:

Patent Family 5

Subject Matter

United States