Monocytic leukemia

TUESDAY, June 18, 2024 -- For children with relapsed or refractory juvenile myelomonocytic leukemia (JMML), trametinib is safe and effective, according to a study published online June 12 in Cancer Discovery . Noting that patients with relapsed or refractory (advanced) JMML have poor outcomes, Elliot Stieglitz, M.D., from the University of California San Francisco, and colleagues examined the safety and efficacy of trametinib, an oral MEK1/2 inhibitor, in a phase 2 trial involving 10 patients with advanced JMML. The researchers found that the objective response rate was 50 percent. After receiving trametinib, four patients with refractory disease proceeded to hematopoietic stem cell transplantation (HSCT). Three additional patients completed all 12 cycles of trametinib permitted in the study and then received trametinib off-protocol, without undergoing HSCT. The remaining three patients had progressive disease; by the end of cycle 2, two of these patients had molecular evolution. "Our trial offered an option for parents who did not want to subject their children to a repeat HSCT and, in some cases, helped patients avoid HSCT entirely," Stieglitz said in a statement. "The findings suggest that trametinib may be a less toxic alternative to HSCT for select patients." Two authors disclosed ties to the biopharmaceutical industry; Novartis provided trametinib for the study.

The Phase IIa study ALICE evaluated the combination of iadademstat plus azacitidine in newly diagnosed, unfit patients with acute myeloid leukemia (AML)The combination showed substantial antileukemic activity with deep responses and a manageable safety profile, including in patients with high-risk prognostic factorsIadademstat continues to be studied in 1L unfit AML patients through an investigator-initiated study with Oregon Health & Science University (OHSU) MADRID and CAMBRIDGE, Mass., June 03, 2024 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today that the final results of the Phase IIa ALICE study evaluating iadademstat in combination with azacitidine in unfit patients with newly diagnosed acute myeloid leukemia (AML) were published online in The Lancet Hematology. A summary of the final data from this study had been previously released in an oral presentation at the 2022 American Society for Hematology (ASH) annual meeting, where it was selected as one of the 25 most relevant communications in AML. This notable publication is a continuation of Oryzon’s previous pioneering research featured in the Journal of Clinical Oncology (First-in-Human study in AML with iadademstat) and Cancer Cell (Characterization of iadademstat as a potent and selective LSD1 inhibitor), cementing the company’s position at the forefront of epigenetics in oncology and LSD1 innovation. Dr. Carlos Buesa, Oryzon’s CEO, stated, “We are thrilled to publish these groundbreaking results in one of the most prestigious journals in clinical oncology. Our study demonstrates that targeting LSD1 is a completely novel anti-leukemic mechanism of action in AML, potentially offering a new therapeutic approach, especially for patients with hard-to-treat forms of the disease such as myelomonocytic leukemias, DNMTs mutations, or TP53 mutations. These patients currently respond poorly to available treatments and may benefit from the innovative treatment option of iadademstat. We want to reiterate our gratitude to the patients, their families and the researchers involved in this study.” Summary of the main results reported in the publication The combination of iadademstat with azacitidine induced a high proportion of responses, with 22 (82%) of 27 patients in the efficacy analysis set having an objective response. Notably, 52% of patients had either a complete remission (CR) or complete remission with incomplete hematological recovery (CRi) in the ALICE trial. For comparison, the percentage of patients who experienced a CR/CRi in the intention-to-treat azacitidine populations was 28% in the acute myeloid leukaemia-001 trial, 28% in the VIALE A trial, and 27% in the Monarch trial.Most of the responses occurred rapidly (87% by the second assessment) and 36% lasted 12 months or longer. At database lock (1 year after the last patient was enrolled), nine patients were alive and as of February, 2024, five patients remain alive, with three continuing treatment (and in complete remission) under compassionate use after four years.The CR/CRi responses in ALICE were generally deep, as determined by the high rate of measurable residual disease (MRD) negativity (91% in the evaluable samples), which is associated with improved survival.Remarkably, responses were seen across the entire adverse prognostic mutational landscape. Of note are the responses in specific subgroups: Three patients with M5 AML (a population primary refractory to venetoclax and azacitidine) had CR/CRi with iadademstat plus azacitidine, with 100% measurable residual disease negativity.In patients with AML with TP53 mutations in combination with a complex karyotype or high variant allele frequency, or both, CR/CRi was reached in 63%, with a duration of response of 7.9 months and a median overall survival of 10 months.Responses in leukemias harboring other poorer-prognosis mutations were also encouraging. All seven patients harboring a mutation or mutations in the RAS pathway responded, with a median overall survival of 467 days. Patients harboring mutations in DNM3TA (n=7), NPM1 (n=4), and RUNX (n=3) had 100% response rates, mostly CR or CRi. A temporary link to access the online publication for free can be found here. As a continuation of ALICE, Oryzon is further expanding the clinical development of iadademstat in 1L unfit AML through an Investigator-initiated study (IIS) led by Oregon Health & Science University (OHSU). This trial is a Phase Ib dose-finding study to evaluate iadademstat in combination with the SoC, venetoclax and azacitidine, in first-line AML patients and is expected to begin enrolling patients in the coming weeks. Iadademstat is currently being evaluated also in combination with gilteritinib in relapsed/refractory AML patients harboring a FLT3 mutation in the FRIDA study, an open-label, multicenter Phase Ib trial being conducted in the US and which plans to accrue up to approximately 45 patients. The first two cohorts have been completed (thirteen patients), and the combination was safe and showed strong antileukemic activity. Following the FDA’s new OPTIMUS doctrine, the company continues to explore the minimal dose with clinical activity, and a third cohort has been started and is recruiting. Preliminary results from this trial will be presented at the upcoming European Hematology Association (EHA) 2024 congress in June. In addition, in neuroendocrine tumors, in the context of the CRADA agreement between Oryzon and the NIH, the NCI is sponsoring a randomized Phase I/II trial in 1L extensive disease small cell lung cancer combining iadademstat with immune checkpoint inhibitors. The IND for this trial was recently approved by the FDA. About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets like HDAC-6, where ORY-4001 has been nominated as clinical candidate for the treatment of certain neurological disorders such as CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About Iadademstat Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and efficacy data in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is being evaluated in a collaborative Phase II basket study with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and the company is preparing a new trial in combination with immune checkpoint inhibitors (ICI) in SCLC. Oryzon has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI) to collaborate on potential further clinical development of iadademstat in different types of solid and hematological cancers; a first trial in combination with ICI in SCLC has recently received FDA IND approval. In total iadademstat has been dosed so far to more than 130 cancer patients in four clinical trials. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This press release is not an offer of securities for sale in the United States or any other jurisdiction. Oryzon’s securities may not be offered or sold in the United States absent registration or an exemption from registration. Any public offering of Oryzon’s securities to be made in the United States will be made by means of a prospectus that may be obtained from Oryzon or the selling security holder, as applicable, that will contain detailed information about Oryzon and management, as well as financial statements. IR, USIR & Media, EuropeSpainOryzonAshley R. RobinsonSandya von der WeidPatricia Cobo/Mario CorderaEmili TorrellLifeSci Advisors, LLCLifeSci Advisors, LLCAtreviaChief Business Officer+1 617 430 7577+41 78 680 05 38+34 91 564 07 25+34 673 33 97 65+34 93 515 1313arr@lifesciadvisors.comsvonderweid@lifesciadvisors.compcobo@atrevia.commcordera@atrevia.cometorrell@oryzon.com

DENVER, May 14, 2024 (GLOBE NEWSWIRE) -- SeaStar Medical Holding Corporation (Nasdaq: ICU) (“SeaStar Medical” or the “Company”), a commercial-stage medical device company developing proprietary solutions to reduce the consequences of hyperinflammation on vital organs, reports financial results for the three months ended March 31, 2024 and provides a business update. “As we guided in late February, we expect initial sales in the coming weeks of Quelimmune™ Pediatric, which is approved for the treatment of pediatric patients with acute kidney injury (AKI) and sepsis or septic condition. Quelimmune has the potential to save lives and improve quality of life by eliminating dialysis dependency through renal recovery for an eligible U.S. pediatric patient population estimated at 4,000 annually,” said Eric Schlorff, SeaStar Medical CEO. “Our launch strategy entails qualifying five prominent children’s hospitals as the first to offer Quelimmune, which will allow us to evaluate its use prior to a more robust commercial rollout that’s planned for the second half of the year. “We are gaining momentum in our NEUTRALIZE-AKI pivotal clinical trial, having now enrolled 31 subjects at eight activated medical sites in this trial that is evaluating the safety and efficacy of our Selective Cytopheretic Device Adult (SCD-ADULT) in the significantly larger U.S. adult AKI patient population that we estimate at 210,000 annually,” he added. “Importantly, we have significantly strengthened our balance sheet having eliminated the senior secured debt and exiting the first quarter with $5 million in cash,” concluded Mr. Schlorff. SeaStar Medical provides the following updates on its commercial and development programs, and corporate activities: Pediatric Acute Kidney Injury Only about half of patients in the pediatric ICU with AKI who require kidney replacement therapy (KRT) survive, with those surviving at risk of long-term, life-threatening conditions such as chronic kidney disease. Pooled analysis from two non-controlled studies, one of which was funded by the FDA Office of Orphan Products Development, showed that children weighing 10 kilograms or more with AKI requiring continuous KRT (CKRT) who were treated with Quelimmune had a 77% survival rate, no dialysis dependency at day 60 and no device-related serious adverse events or device-related infections. In February 2024 SeaStar Medical received its first U.S. regulatory approval for Quelimmune (SCD Pediatric) device for children with AKI and sepsis or septic condition weighing 10 kilograms or more who are being treated in the ICU with KRT. Quelimmune was approved under a humanitarian device exemption (HDE) application, having met the applicable criteria with clinical results showing safety and probable clinical benefit to critically ill children with AKI who have few treatment options. The U.S. addressable population of about 4,000 pediatric patients falls within the 8,000-patient HDE criteria.The Company is working with its current partner to commercialize Quelimmune under HUD requirements. Pediatric patients undergoing treatment with Quelimmune are expected to require on average seven Quelimmune daily therapies, with the disposable device being changed once every 24 hours.In March 2024 the Company sponsored an industry symposium titled “New Therapies in Pediatric Acute Kidney Injury” at the AKI & CRRT 2024 conference. The symposium featured key opinion leaders in nephrology and AKI, who are members of the Company’s Scientific Advisory Board. Adult Acute Kidney Injury SeaStar Medical is conducting the pivotal NEUTRALIZE-AKI (NEUTRophil and Monocyte DeActivation via SeLective CytopheretIc Device - a RandomiZEd Clinical Trial in Acute Kidney Injury) clinical trial to evaluate the safety and effectiveness of the SCD in adults with AKI in the ICU receiving CKRT. The SCD-ADULT has received FDA Breakthrough Device Designation for adult AKI. This designation is awarded to a therapy to treat a serious or life-threatening condition with preliminary clinical evidence indicating it may demonstrate substantial improvement over available therapies on clinically significant endpoints. The NEUTRALIZE-AKI trial is expected to enroll up to 200 patients at up to 30 U.S. medical centers. The trial’s primary endpoint is a composite of 90-day mortality or dialysis dependency of patients treated with SCD-ADULT in addition to CKRT as the standard of care, compared with the control group receiving only CKRT standard of care. Secondary endpoints include mortality at 28 days, ICU-free days in the first 28 days, major adverse kidney events at Day 90 and dialysis dependency at one year. The study will also include subgroup analyses to explore the effectiveness of SCD-ADULT therapy in AKI patients with sepsis and acute respiratory distress syndrome. A more complete description of the NEUTRALIZE-AKI trial design can be found in the journal Nephron.The Company expects to receive regulatory approval under a Premarket Approval (PMA) application for the SCD-ADULT in the second half of 2025 and to launch the product in the first half of 2026. Additional SCD Indications SeaStar Medical continues to explore the application of its SCD technology across a range of indications involving dysregulated immune processes where proinflammatory activated neutrophils and monocytes may contribute to disease progression or severity, in both acute and chronic indications. In September 2023 the Company received Breakthrough Device Designation for the SCD for use in cardiorenal syndrome. This was only the ninth Breakthrough Device Designation granted by the FDA’s Center for Biologics Evaluation and Research since the program’s inception in 2015.In October 2023 the Company received Breakthrough Device Designation for the SCD for use in hepatorenal syndrome. An ongoing pilot study in this indication at the University of Michigan is expected to provide valuable insight in the design and execution of a pivotal study.In February 2024 the manuscript “New Opportunity for Targeting Systemic Inflammation in Patients with Heart Failure through Leukocyte Immunomodulation” Pitt, B., Iyer, S.P.N. and Humes, H.D. discussing the role of chronic dysregulated systemic inflammation in heart failure and the potential application of the SCD was published in the peer-reviewed European Journal of Heart Failure.In April 2024 the National Institutes of Health awarded a $3.6 million grant for a clinical trial to evaluate the SCD-ADULT as a bridging strategy to left ventricular assist device implantation in patients with chronic heart failure who have progressed to acute decompensated heart failure. This grant was awarded to Innovative BioTherapies, which is led by SCD inventor H. David Humes, M.D., Professor, Division of Nephrology, Internal Medicine, University of Michigan and SeaStar Medical Scientific Advisor. SeaStar Medical is expected to directly receive approximately one-quarter of the grant for serving as the contract research organization for the trial. By building out this competency, it can be leveraged for other clinical studies, potentially reducing the overall cost of clinical programs. Corporate Developments In January 2024 the Company appointed healthcare industry veteran David A. Green as Chief Financial Officer. Mr. Green brings to SeaStar Medical extensive financial experience at public medical device and therapeutics companies.In January 2024 the Company announced a $9.0 million registered direct offering priced at-the-market.In January 2024 a U.S. patent was granted with broad claims directed to methods of using the SCD to treat subjects with inflammatory conditions and to process activated leukocytes and platelets.In February 2024 the Canadian Intellectual Property Office issued a patent with broad claims covering the SCD technology. First Quarter Financial Results Research and development (R&D) expenses for the first quarters of 2024 and 2023 were relatively consistent at $1.7 million. General and administrative (G&A) expenses for the first quarter of 2024 were $2.3 million, compared with $2.9 million for the first quarter of 2023, with the decrease due to reductions in accounting, finance, legal and SEC-related fees, sales and marketing expenses, insurance fees, other business expenses primarily due to a legal settlement in the prior-year quarter, and slightly lower personnel and consulting costs. Other expense for the first quarter of 2024 was $8.8 million (of which $8.7 million related to non-cash losses from derivative financial instruments), compared with $2.5 million for the first quarter of 2023. The increase was primarily related to the extinguishment of convertible notes, change in the fair value of liability classified warrants, issuance of convertible notes, and increase in the fair value of convertible notes. This was offset by a recognized loss on a forward purchase agreement derivative liability at March 31, 2023, which no longer exists in 2024, and reduction in interest expense as a result of both paying down notes payable and converting all but $1.1 million in convertible notes as of March 31, 2024. The net loss for the first quarter of 2024 was $12.7 million, or $0.19 per share on 67.1 million weighted-average shares outstanding. This compared with a net loss for the first quarter of 2023 of $7.1 million, or $0.54 per share, on 13.0 million weighted-average shares outstanding. The Company reported cash of $5.0 million as of March 31, 2024, compared with $176,000 as of December 31, 2023. In January 2024 the Company announced a $9.0 million registered direct offering priced at-the-market. About Hyperinflammation Hyperinflammation is the overproduction or overactivity of inflammatory cells that can lead to damage of vital organs. It occurs when the body overproduces inflammatory effector cells and other molecules that can be toxic, damaging to vital organs and result in multi-organ failure and even death. This is known as the cytokine storm. About the Selective Cytopheretic Device The SCD is a patented cell-directed extracorporeal device that employs immunomodulating technology to selectively target proinflammatory neutrophils and monocytes during CKRT and reduces the hyperinflammatory milieu including the cytokine storm that causes inflammation, organ failure and possible death in critically ill patients. Unlike pathogen removal and other blood-purification tools, the SCD is integrated with CKRT hemofiltration systems to selectively target and transition proinflammatory monocytes to a reparative state and promote activated neutrophils to be less inflammatory. The SCD selectively targets the most highly activated proinflammatory neutrophils and monocytes. These cells are then returned back into the body through the blood, and the body is signaled to lower its inflammatory environment and focus on repair. This unique immunomodulation approach may promote long-term organ recovery and eliminate the need for future KRT, including dialysis. Quelimmune is the official brand name for the SCD Pediatric that has received FDA HDE approval based on safety and probable efficacy. About SeaStar Medical SeaStar Medical is a commercial-stage medical technology company that is redefining how extracorporeal therapies may reduce the consequences of excessive inflammation on vital organs. SeaStar Medical’s novel technologies rely on science and innovation to provide life-saving solutions to critically ill patients. The Company is developing and commercializing cell-directed extracorporeal therapies that target the effector cells that drive systemic inflammation, causing direct tissue damage and secreting a range of pro-inflammatory cytokines that initiate and propagate imbalanced immune responses. For more information visit www.seastarmedical.com or visit us on LinkedIn or X. Forward-Looking Statements This press release 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 ability of SCD to treat patients with AKI and other diseases; the expected regulatory approval process and timeline for commercialization; and the ability of SeaStar Medical to meet the expected timeline. 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 Medical may not be able to obtain regulatory approval of its SCD product candidates; (ii) the risk that SeaStar Medical may not be able to raise sufficient capital to fund its operations, including current or future 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, (viii) the risk that SeaStar Medical is unable to secure or protect its intellectual property, and (ix) 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 assumes 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. Contact:LHA Investor RelationsJody Cain(310) 691-7100Jcain@lhai.com Financial Tables to FollowSeaStar Medical Holding CorporationCondensed Consolidated Balance Sheets(in thousands, except for share and per-share amounts) March 31,2024 December 31,2023 (unaudited) ASSETSCurrent assets Cash $5,019 $176 Prepaid expenses 1,518 2,132 Total current assets 6,537 2,308 Other assets 1,203 1,205 Total assets $7,740 $3,513 LIABILITIES AND STOCKHOLDERS' DEFICIT Current liabilities Accounts payable $3,879 $4,372 Accrued expenses 1,544 1,523 Contingent upfront payment for license agreement 100 100 Notes payable, net of deferred financing costs 357 565 Convertible notes, current portion 1,135 4,179 Liability classified warrants 2,633 2,307 Total current liabilities 9,648 13,046 Notes payable, net of deferred financing costs 2,565 4,143 Convertible notes, net of current portion — 194 Total liabilities 12,213 17,383 Commitments and contingencies (Note 9) Stockholders' deficit Preferred stock - $0.0001 par value, 10,000,000 shares authorized at March 31, 2024 and December 31, 2023; no shares issued and outstanding at March 31, 2024 and December 31, 2023 — — Common stock - $0.0001 par value per share; 500,000,000 shares authorized; 75,419,458 and 47,615,285 shares issued and outstanding at March 31, 2024 and December 31, 2023, respectively 8 5 Additional paid-in capital 122,950 100,859 Accumulated deficit (127,431) (114,734)Total stockholders' deficit (4,473) (13,870)Total liabilities and stockholders' deficit $7,740 $3,513 SeaStar Medical Holding CorporationCondensed Consolidated Statements of Operations(unaudited)(in thousands, except for share and per-share amounts) Three Months Ended March 31, 2024 2023 Operating expenses Research and development $1,697 $1,730 General and administrative 2,253 2,851 Total operating expenses 3,950 4,581 Loss from operations (3,950) (4,581)Other income (expense) Interest expense (143) (433)Change in fair value of convertible notes (5,758) 100 Change in fair value of warrants liability (2,846) 36 Change in the fair value of the forward purchase agreement derivative liability — (2,218)Total other income (expense), net (8,747) (2,515)Loss before provision for income taxes (12,697) (7,096)Provision for income taxes — — Net loss $(12,697) $(7,096)Net loss per share of common stock, basic and diluted $(0.19) $(0.54)Weighted-average shares outstanding, basic and diluted 67,106,081 13,025,852 SeaStar Medical Holding CorporationCondensed Consolidated Statements of Cash Flows(unaudited)(in thousands, except for shares and per-share amounts) Three Months Ended March 31, 2024 2023 Cash flows from operating activities Net loss $(12,697) $(7,096)Adjustments to reconcile net loss to net cash used in operating activities Amortization of deferred financing costs 27 4 Change in fair value of convertible notes (issued, converted and outstanding) 5,758 2,218 Change in fair value of forward purchase agreement derivative liability — (100)Change in fair value of liability classified warrants (exercised and outstanding) 2,846 (36)Stock-based compensation 434 505 Changes in operating assets and liabilities Other receivables — 12 Prepaid expenses 614 318 Other assets 2 — Accounts payable (493) 1,095 Accrued expenses 21 — Other liabilities — 786 Net cash used in operating activities (3,488) (2,294) Cash flows from financing activities Proceeds from issuance of convertible notes 979 3,000 Payment of convertible notes — (10)Proceeds from issuance of shares 4,543 1,108 Proceeds from exercise of convertible note warrants 853 — Proceeds of Pre-Funded warrants 3,769 — Payment of commitment fee - equity line of credit — (500)Proceeds from sale of recycled shares — 1,870 Proceeds from notes payable — 100 Payment of notes payable (1,813) (2,596)Net cash provided by financing activities 8,331 2,972 Net increase in cash 4,843 678 Cash, beginning of period 176 47 Cash, end of period $5,019 $725 # # #