PAI-1 inhibitors(Plasminogen activator inhibitor 1 inhibitors), tPA stimulants(plasminogen activator, tissue type stimulants), vWF inhibitors(Von willebrand factor inhibitors)

Therapeutic Areas

Cardiovascular DiseasesDigestive System DisordersOther Diseases+ [4]

Active Indication

Venoocclusive diseaseHepatic Veno-Occlusive DiseaseHigh Risk Neuroblastoma+ [2]

Inactive Indication

Acute Graft Versus Host DiseaseDiffuse large B-cell lymphoma recurrentLiver Injury+ [2]

Originator Organization

Gentium Srl

Active Organization

Jazz Pharmaceuticals Plc

Nippon Shinyaku Co., Ltd.

Gentium Srl

+ [1]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

EU (18 Oct 2013),

Hepatic Veno-Occlusive Disease

RegulationFast Track (US), Orphan Drug (US), Orphan Drug (EU), Orphan Drug (AU)

Clinical Trials associated with Defibrotide Sodium

NCT06182410 / Not yet recruitingPhase 2IIT

Defibrotide Prophylaxis of Transplant Associated-Thrombotic Microangiopathy in Patients With High-Risk Neuroblastoma Receiving Tandem Transplants

This phase II trial tests how well defibrotide works in preventing transplant-associated thrombotic microangiopathy (TA-TMA) in patients with high-risk neuroblastoma undergoing tandem transplants (hematopoietic stem cell transplant [HSCT]). TMA is a potential life-threatening complication of stem cell transplant. TMA is a possible side effect of the chemotherapy (conditioning regimen) patients receive to help treat high-risk neuroblastoma, because these medicines can sometimes damage the blood vessel walls in the body. This damage leads to formation of tiny blood clots in organs, especially the kidney. This then causes organ damage and leads to problems with how they function. This study may help researchers learn how defibrotide may help prevent TMA before it starts, or help treat it once it starts among patients with high-risk neuroblastoma undergoing tandem transplants.

Start Date01 Jun 2024

Sponsor / Collaborator

The University of California, San Francisco

[+1]

NCT05987124 / RecruitingPhase 2IIT

A Phase II Intrapatient Open-Label Dose Escalation Trial of Defibrotide in Hematopoietic Cell Transplantation (HCT) Recipients With Sinusoidal Obstructive Syndrome (SOS) Post-HCT Associated With Either Renal and/or Pulmonary Dysfunction With Either Refractory or Progressive Disease Following Defibrotide Therapy

This research study is being done to determine the safety and tolerability of increasing doses of defibrotide within a single patient with sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) after hematopoietic cell transplantation (HCT) associated with either kidney and/or lung impairment that has not obtained a complete response (CR) or progressed in severity with standard doses of defibrotide.

Start Date20 Mar 2024

Sponsor / Collaborator

New York Medical College

NCT04313036 / Unknown statusPhase 2IIT

Phase II Open Label Study to Assess Efficacy of 5-day Defibrotide Treatment for Hepatic SOS/VOD

Sinusoidal Obstruction Syndrome (SOS), also referred to as hepatic veno-occlusive disease (VOD), is rare but serious complication of allogeneic stem cell transplantation (allo-SCT). Defibrotide is the only FDA approved therapy to treat SOS and has significantly improved outcomes. When applied early, SOS symptoms often quickly improve and an abbreviated course can be applied. This study is looking at an abbreviated 5 day course of defibrotide in those patients with a complete response to therapy with the primary outcome being day 100 overall survival as compared to history data.

Start Date11 Mar 2021

Sponsor / Collaborator-

100 Clinical Results associated with Defibrotide Sodium

100 Translational Medicine associated with Defibrotide Sodium

100 Patents (Medical) associated with Defibrotide Sodium

577

Literatures (Medical) associated with Defibrotide Sodium

01 Mar 2024·Current opinion in rheumatology

Recent advances on neutrophil dysregulation in the pathogenesis of rheumatic diseases

Review

Author: Chen, Jianing ; Zhang, Xuan ; Liu, Yudong ; Wang, Xinyu

Purpose of review:

The exact pathogenic mechanisms of rheumatic diseases (RMD) remain largely unknown. Increasing evidence highlights a pathogenic role of neutrophil dysregulation in the development of RMD.

Recent findings:

The purpose of this review is to present a current overview of recent advancements in understanding the role of neutrophil dysfunction in the development of RMD. Additionally, this review will discuss strategies for targeting pathways associated with neutrophil dysregulation as potential treatments for RMD. One specific aspect of neutrophil dysregulation, known as neutrophil extracellular traps (NETs), will be explored. NETs have been found to contribute to chronic pulmonary inflammation and fibrosis, as well as serve as DNA scaffolds for binding autoantigens, including both citrullinated and carbamylated autoantigens. Putative therapies, such as 6-gingerol or defibrotide, have demonstrated beneficial effects in the treatment of RMD by suppressing NETs formation.

Summary:

Recent advances have significantly reinforced the crucial role of neutrophil dysregulation in the pathogenesis of RMD. A deeper understanding of the potential mechanisms underlying this pathogenic process would aid in the development of more precise and effective targeting strategies, thus ultimately improving the outcomes of RMD.

01 Feb 2024·Annals of hematology

Liver failure after treatment with inotuzumab and polychemotherapy including PEG-asparaginase in a patient with relapsed Philadelphia chromosome–negative acute lymphoblastic leukemia

Article

Author: Fischer, Daniel ; Bug, Gesine ; Gökbuget, Nicola ; Michalik, Sabine ; Lang, Fabian ; Toenges, Rosa ; Thalhammer, Axel ; Kiil, Kati

Abstract:

We present the case of a 58-year-old female patient who presented with an extramedullary B-ALL relapse after prior allogenic HSCT and blinatumomab therapy. The patient died from complications of a drug-induced acute liver failure after a salvage therapy combining inotuzumab ozogamicin (InO)-based induction followed by consolidation with high dose MTX and pegaspargase based on the GMALL protocol for older ALL patients. After a diagnosis of the extramedullary relapse in the form of a retro vesical chloroma, the patient received an individualized multi-agent chemotherapy based on induction chemotherapy for older patients in combination with InO. After four administrations of InO, in combination with vincristine, dexamethasone, cytarabine, and cyclophosphamide, CT-imaging showed a reduction in volume of the chloroma and response to therapy. Consolidation with high-dose methotrexate and pegaspargase was administered. The patient developed toxic liver damage manifested by hyperbilirubinemia and progressive hepatic encephalopathy. The diagnostic criteria for VOD were met, and therapy with defibrotide was initiated. Liver biopsy revealed no histological signs of VOD but instead steatohepatitis indicative of drug-induced toxicity. The patient ultimately died of hemorrhagic shock through postinterventional hemorrhage after liver biopsy. In conclusion, although InO shows promising results in the therapy of r/r ALL with and without additional chemotherapy, the combination with MTX and pegaspargase in an intensively pretreated patient with relapse after HCST may impart an increased risk for liver-related toxicity. Special caution is required when assessing fitness for further liver toxic regimens. A key takeaway is also the reminder that InO can cause liver damage not only in the form of VOD but also through direct hepatocellular toxicity.

01 Feb 2024·Transplant immunology

sVEGF-R1 in acute non-infectious toxicity syndromes after pediatric allogeneic hematopoietic stem cell transplantation

Article

Author: Ifversen, Marianne ; Müller, Klaus ; Kammersgaard, Marte B ; Weischendorff, Sarah Wegener ; Johansson, Pär I ; Ryder, Lars P ; Sørum, Maria Ebbesen ; Kielsen, Katrine ; Nielsen, Claus ; Horan, Denise Elbæk

BACKGROUND:

Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute non-infectious toxicities, including sinusoidal obstruction syndrome (SOS), engraftment syndrome (ES) and capillary leak syndrome (CLS) among others. These complications are thought to be driven by a dysfunctional vascular endothelium, but the pathophysiological mechanisms remain incompletely understood, and the diagnoses are challenged by purely clinical diagnostic criteria that are partly overlapping, limiting the possibilities for progress in this field. There is, however, increasing evidence suggesting that these challenges may be met through the development of diagnostic biomarkers to improve diagnostic accuracy of pathogenetically homogenous entities, improved pre-transplant risk assessment and the early identification of patients with increased need for specific treatment. Soluble vascular endothelial growth factor receptor-1 (sVEGF-R1) is emerging as an important biomarker of endothelial damage in patients with trauma and sepsis but has not been studied in HSCT.

OBJECTIVES:

To investigate sVEGF-R1 as a marker of endothelial damage in pediatric HSCT patients by exploring associations with SOS, CLS, ES, and acute graft-versus-host disease (aGvHD).

METHODS:

We prospectively included 113 children undergoing myeloablative HSCT and measured sVEGF-R1 in plasma samples obtained weekly during the early period of transplantation and 3 months post-transplant.

RESULTS:

All over, sVEGF-R1 levels were significantly increased from day +7 after graft infusion, peaking at day +30, most pronounced in patients receiving busulfan. Patients considered to be at increased risk of SOS and therefore commenced on prophylactic defibrotide had significantly elevated levels of sVEGF-R1 before start of conditioning (446 pg/mL vs. 281 pg/mL, p = 0.0035), and this treatment appeared to stabilize sVEGF-R1 levels compared to patients not treated with defibrotide. Thirteen (11.5%) children meeting the modified Seattle criteria for SOS at median day +8 (1-18), had significantly elevated sVEGF-R1 levels on day +14 (489 pg/mL vs. 327 pg/mL, p = 0.007). In contrast. sVEGF-R1 levels in the much broader group of patients (45.1%) meeting EBMT-SOS criteria, including patients with very mild disease, did not overall differ in sVEGF-R1 levels, but higher sVEGF-R1 levels were seen in EBMT-SOS patients with an increased need for diuretic treatment. Importantly, sVEGF-R1 levels were not associated with ES and CLS but were significantly increased on day +30 in patients with grade III-IV aGvHD (OR = 4.2 pr. quartile, p = 0.023).

CONCLUSION:

VEGF-R1 levels are found to be increased in pediatric patients developing SOS, reflecting the severity of morbidity. sVEGF-R1 were unassociated with both CLS and ES. The potential of sVEGF-R1 as a clinically useful biomarker for SOS should be further explored to improve pre-transplant SOS-risk assessment, SOS-severity grading, and to guide treatment.

News (Medical) associated with Defibrotide Sodium

10 Dec 2023

·www.biospace.com

Long-Term Data Presented at ASH Support beti-cel as a Potentially Curative Gene Therapy for β-Thalassemia Patients Who Require Regular Transfusions Through Achievement of Durable Transfusion Independence and Normal or Near-Normal Adult Hb Levels

Updated data from studies of beti-cel in 63 patients with transfusion-dependent beta-thalassemia showed sustained transfusion independence and improvements in iron management through up to 9 years of follow-up (n=1) All four parent studies are complete, and all patients have transitioned to a long-term follow-up study (LTF-303) beti-cel is U.S. Food and Drug Administration (FDA) approved and marketed in the U.S. as ZYNTEGLO SOMERVILLE, Mass.--(BUSINESS WIRE)-- Updated data from bluebird bio inc.’s (NASDAQ: BLUE) gene therapy program in transfusion-dependent (TDT) beta-thalassemia were presented today at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition. Updated follow-up data showed sustained treatment effect, reduced iron management burden and improved quality of life measures in patients with beta-thalassemia who require regular red blood cell transfusions following treatment with betibeglogene autotemcel (beti-cel) (FDA approved and marketed in the U.S. as ZYNTEGLO™). “Long-term results presented at ASH 2023 showed durable transfusion independence and a continued positive safety pro patients with beta-thalassemia treated with our beti-cel gene therapy through up to nine years of follow-up,” said Richard Colvin, M.D., Ph.D., chief medical officer, bluebird bio. “These data represent the longest follow-up with a gene therapy for patients with beta-thalassemia requiring regular transfusions and continue to show that beti-cel is a potentially curative therapy across ages and genotypes, through the achievement of durable transfusion independence and normal or near-normal hemoglobin levels.” As of January 30, 2023, 63 patients had received beti-cel across four clinical studies with a median follow-up of 5 years (60.1 months; range: 23.8-109.5). These include two Phase 3 studies (N=41) that led to the FDA approval of ZYNTEGLO in August 2022 as the first and only gene therapy for patients with beta-thalassemia who require regular red blood cell transfusions. Sustained Efficacy and Safety Results, and Improved Quality of Life Measures in Adult and Pediatric Patients With Transfusion-Dependent β-Thalassemia Up to 9 Years Post Treatment With Betibeglogene Autotemcel (beti-cel) (poster #1102) Among patients in the Phase 3 studies, 90.2% (37/41) achieved transfusion independence (TI). As of the data cutoff date, TI was maintained through last follow-up (up to 6 years) across ages and genotypes. Among patients in the Phase 1/2 studies, 68.2% (15/22) achieved TI, with 14 patients sustaining TI through the last follow-up (up to 9 years). One patient, with human immunodeficiency virus complicated by gastrointestinal infection and bleeding, no longer met protocol-defined TI as a result of a hemoglobin level <9 g/dL at year 6. The patient continued to benefit from beti-cell therapy and was not receiving chronic red blood cells transfusions as of the last follow-up. Among 12 adult patients and 22 pediatric patients in the Phase 1/2 and Phase 3 studies, health-related quality of life (HRQOL) was assessed at baseline and every 6 months. Clinically meaningful improvements in quality of life assessments, including various quality of life assessments for mental, physical and psychosocial health, were demonstrated in both adult and pediatric patients up to 36 months. As of the cutoff date, the safety results following beti-cel treatment largely reflected the known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. Overall, 19% of patients experienced ≥1 beti-cel-related AE. The most common beti-cel-related AEs (occurring in ≥3 patients) were abdominal pain (7.9% of patients) and thrombocytopenia (4.8% of patients). Five patients experienced serious veno-occlusive liver disease; all 5 received defibrotide and recovered. No malignancies, insertional oncogenesis, or vector-derived replication-competent lentivirus were reported. Improvement in Iron Burden in Patients With Transfusion-Dependent β-Thalassemia (TDT) Treated With Betibeglogene Autotemcel (beti-cel) Gene Therapy: Up to 9 Years of Follow-Up (poster #2480) Additionally, iron management outcomes were presented from patients with transfusion-dependent beta-thalassemia who completed either a Phase 1/2 or Phase 3 beti-cel parent study and subsequently enrolled in the long-term follow-up study and were followed for up to 9 years. Across all studies, 37/51 patients restarted chelation, and 12 received phlebotomy post-infusion; however, 69% (35/51) were able to stop chelation therapy, demonstrating restoration of iron levels over time and reduced iron management burden in those patients. About ZYNTEGLO™ (betibeglogene autotemcel) or beti-cel ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene therapy. It is approved for the treatment of beta-thalassemia in adult and pediatric patients who require regular red blood cell transfusions and was launched commercially more than a year ago. ZYNTEGLO works by adding functional copies of a modified form of the beta-globin gene (βA-T87Q-globin gene) into a beta-thalassemia patient’s own hematopoietic (blood) stem cells to enable the production of a modified functional adult hemoglobin (HbAT87Q). Once a patient has the βA-T87Q-globin gene, they have the potential to increase ZYNTEGLO-derived adult hemoglobin (HbAT87Q) and total hemoglobin to normal or near normal levels that can eliminate the need for regular red blood cell (RBC) transfusions. Indication ZYNTEGLO is indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular red blood cell (RBC) transfusions. Important Safety Information Delayed Platelet Engraftment Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets on or after Day 100. Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise. Risk of Neutrophil Engraftment Failure There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells. Risk of Insertional Oncogenesis There is a potential risk of LVV mediated insertional oncogenesis after treatment with ZYNTEGLO. Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, and integration site analysis at Months 6, 12, and as warranted. In the event that a malignancy occurs, contact bluebird bio at 1 833-999-6378 for reporting and to obtain instructions on collection of samples for testing. Hypersensitivity Reactions Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis. Anti-retroviral and Hydroxyurea Use Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells. Interference with Serology Testing Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV. Therefore, patients who have received ZYNTEGLO should not be screened for HIV infection using a PCR-based assay. Adverse Reactions The most common non-laboratory adverse reactions (≥20%) were mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (>50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia. Drug Interactions Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates. Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate. Pregnancy/Lactation Advise patients of the risks associated with conditioning agents, including on pregnancy and fertility. ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician. ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician. Females and Males of Reproductive Potential A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration. Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO. Advise patients of the option to cryopreserve semen or ova before treatment if appropriate. Please see full Prescribing Information for ZYNTEGLO. About bluebird bio bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days. Founded in 2010, bluebird has been setting the standard for gene therapy for more than a decade—first as a scientific pioneer and now as a commercial leader. bluebird has an unrivaled track record in bringing the promise of gene therapy out of clinical studies and into the real-world setting, having secured FDA approvals for three therapies in under two years. Today, we are proving and scaling the commercial model for gene therapy and delivering innovative solutions for access to patients, providers, and payers. With a dedicated focus on severe genetic diseases, bluebird has the largest and deepest ex-vivo gene therapy data set in the field, with industry-leading programs for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward. bluebird continues to forge new paths as a standalone commercial gene therapy company, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds. bluebird bio Cautionary Statement Regarding Forward-Looking Statements Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements, such as statements regarding beti-cel as a potentially curative therapy across ages and genotypes. Such forward-looking statements are based on historical performance and current expectations and projections about bluebird’s future goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond bluebird’s control and could cause bluebird’s future goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect bluebird bio’s business, particularly those identified in the risk factors discussion in bluebird bio’s Annual Report on Form 10-K for the year ended December 31, 2022, as updated by its subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. These risks and uncertainties include, but are not limited to: delays and challenges in bluebird’s commercialization and manufacturing of its products; the internal and external costs required for bluebird’s ongoing and planned activities, and the resulting impact on expense and use of cash, has been, and may in the future be, higher than expected which has caused bluebird, and may in the future cause bluebird to use cash more quickly than it expects or change or curtail some of its plans or both; substantial doubt exists regarding bluebird’s ability to continue as a going concern; bluebird’s expectations as to expenses, cash usage and cash needs may prove not to be correct for other reasons such as changes in plans or actual events being different than its assumptions; the risk that the efficacy and safety results from bluebird’s prior and ongoing clinical trials will not continue or be seen in the commercial context; and the risk of insertional oncogenic or other safety events associated with lentiviral vector, drug product, or myeloablation. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, bluebird bio undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. View source version on businesswire.com: Contacts Investors: Courtney O’Leary, 978-621-7347 coleary@bluebirdbio.com Media: Jess Rowlands, 857-299-6103 jess.rowlands@bluebirdbio.com Source: bluebird bio, Inc. View this news release online at:

Clinical ResultPhase 3ASHDrug ApprovalGene Therapy

30 Nov 2023

·www.prnewswire.com

Jazz Pharmaceuticals to Present New Data Highlighting Advancements in Solid Tumors and Rare Blood Cancers at Upcoming Oncology Meetings

New trial results of investigational bispecific antibody zanidatamab presented at SABCS in HER2+/HR+ metastatic breast cancer Strong presence at ASH includes 11 presentations spanning Jazz's portfolio, advancing research into difficult-to-treat blood cancers and diseases Real-world data at NACLC reinforce clinical impact of Zepzelca® (lurbinectedin) in small cell lung cancer DUBLIN, Nov. 30, 2023 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the Company and its partners will present two abstracts at the 2023 San Antonio Breast Cancer Symposium (SABCS) from December 5-9; 11 abstracts at the 65th Annual American Society of Hematology (ASH) Annual Meeting from December 9-12; and two abstracts at the International Association for the Study of Lung Cancer (IASLC) 2023 North America Conference on Lung Cancer (NACLC) from December 1-3. New data include updated findings from a Phase 2a trial of the investigational HER2-targeted bispecific antibody zanidatamab in combination with palbociclib and fulvestrant as a chemotherapy-free option for HER2+/ HR+ metastatic breast cancer (mBC). "Following recent trial results showing the potential of zanidatamab to treat HER2-expressing gastric and biliary tract cancers at ASCO GI, ASCO and ESMO this year, we're excited to share updated data at SABCS in HER2-amplified and hormone receptor-positive metastatic breast cancer when zanidatamab is used in combination to target the HER2, CDK4/6 and hormone receptor pathways," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "SABCS will also feature data from a trial of zanidatamab in neoadjuvant breast cancer. Additionally, we look forward to sharing new data through numerous presentations at ASH 2023 that underscore our commitment to improving standards of care in blood cancer and other hematologic diseases, as well as real-world findings at NACLC that provide evidence of Zepzelca's safety in clinical practice for the treatment of second-line small cell lung cancer." Notable presentations at this year's SABCS, ASH and NACLC meetings include: A SABCS oral presentation (late-breaking abstract) featuring primary results from a Phase 2a study for a chemotherapy-free option in heavily pretreated patients with HER2+/HR+ mBC treated with the combination of zanidatamab plus palbociclib and fulvestrant. An investigator-sponsored (MD Anderson Cancer Center) SABCS poster presentation featuring results of a Phase 1 trial evaluating neoadjuvant zanidatamab in patients with stage 1 node-negative HER2+ breast cancer as a single-agent chemotherapy-free option. An ASH poster presentation of the complete pivotal, Phase 2/3 trial results of Rylaze® (asparaginase erwinia chrysanthemi (recombinant)-rywn) in acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL), which includes efficacy, safety and population pharmacokinetic modeling from intramuscular (IM) and intravenous (IV) dosing. The combination of observed and modeled results demonstrates Rylaze achieved therapeutic nadir serum asparaginase activity (NSAA) levels in the vast majority of patients via multiple dosing schedules with a safety profile consistent with prior studies and no new safety signals identified. Treatment‐related adverse events (TRAEs) ≥ grade 3 occurred in 126/228 (55%) patients with no TRAEs that led to death.1 Two NACLC poster presentations of real-world data for Zepzelca® (lurbinectedin) in the second-line and later settings for the treatment of small cell lung cancer (SCLC). The Jazz and partner-supported presentations at SABCS 2023 are: Zanidatamab Presentations The Jazz-supported presentations at the 2023 ASH Annual Meeting are: Rylaze Presentations Asparaginase Collaboration Studies Vyxeos Presentations Defitelio Presentations The Jazz-supported presentations at NACLC 2023 are: Zepzelca Presentations About Zanidatamab Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China. About RYLAZE ® (asparaginase erwinia chrysanthemi (recombinant)-rywn) RYLAZE, also known as JZP458, is approved in the U.S. for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients one month or older who have developed hypersensitivity to E. coli-derived asparaginase. RYLAZE has orphan drug designation for the treatment of ALL/LBL in the United States. RYLAZE, or recombinant Erwinia is a short-acting distinct asparaginase derived from a novel Pseudomonas fluorescens expression platform to help ensure robustness of supply to meet patient needs. JZP458 was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in October 2019 for the treatment of this patient population. RYLAZE was approved as part of the Real-Time Oncology Review program, an initiative of the FDA's Oncology Center of Excellence designed for efficient delivery of safe and effective cancer treatments to patients.2 The full U.S. Prescribing Information for RYLAZE is available at: Important Safety Information for Rylaze RYLAZE should not be given to people who have had: Serious allergic reactions to RYLAZE Serious swelling of the pancreas (stomach pain), serious blood clots, or serious bleeding during previous asparaginase treatment RYLAZE may cause serious side effects, including: Allergic reactions (a feeling of tightness in your throat, unusual swelling/redness in your throat and/or tongue, or trouble breathing), some of which may be life-threatening Swelling of the pancreas (stomach pain), which, if left untreated, may be fatal Blood clots (may be experienced as headache, arm or leg swelling, shortness of breath, or chest pain), which may be life-threatening Bleeding, which may be life-threatening Liver problems Contact your doctor immediately if any of these side effects occur. Some of the most common side effects with RYLAZE include: liver problems, nausea and vomiting, bone and muscle pain, infection, tiredness, headache, fever with low white blood cell count, fever, bleeding, mouth swelling (sometimes with sores), pain in the abdomen, decreased appetite, allergic reactions, high blood sugar levels, diarrhea, swelling of the pancreas, and low levels of potassium in your blood. RYLAZE can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Females of reproductive potential should use effective contraception (other than hormonal contraceptives) during treatment and for 3 months following the final dose. Do not breastfeed while receiving RYLAZE and for 1 week after the final dose. Tell your healthcare provider if there are any side effects that are bothersome or that do not go away. These are not all the possible side effects of RYLAZE. For more information, ask your healthcare provider. Call your doctor for medical advice about any side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088 (1-800-332-1088). About Vyxeos ® (daunorubicin and cytarabine) liposome for injection Vyxeos is a liposomal combination of daunorubicin, an anthracycline topoisomerase inhibitor, and cytarabine, a nucleoside metabolic inhibitor. In the U.S., Vyxeos (daunorubicin and cytarabine) liposome for injection is indicated for the treatment of newly-diagnosed therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC) in adults and pediatric patients 1 year and older.3 More information about Vyxeos in the United States, including Full Prescribing Information and BOXED Warning, is available here. Important Safety Information for VYXEOS ® WARNING: VYXEOS has different dosage recommendations from other medications that contain daunorubicin and/or cytarabine. Do not substitute VYXEOS for other daunorubicin and/or cytarabine-containing products. VYXEOS should not be given to patients who have a history of serious allergic reaction to daunorubicin, cytarabine, or any of its ingredients. VYXEOS can cause a severe decrease in blood cells (red and white blood cells and cells that prevent bleeding, called platelets) which can result in serious infection or bleeding and possibly lead to death. Your doctor will monitor your blood counts during treatment with VYXEOS. Patients should tell the doctor about new onset fever or symptoms of infection or if they notice signs of bruising or bleeding. VYXEOS can cause heart-related side effects. Tell your doctor about any history of heart disease, radiation to the chest, or previous chemotherapy. Inform your doctor if you develop symptoms of heart failure such as: shortness of breath or trouble breathing swelling or fluid retention, especially in the feet, ankles, or legs unusual tiredness VYXEOS may cause allergic reactions including anaphylaxis. Seek immediate medical attention if you develop signs and symptoms of anaphylaxis such as: trouble breathing severe itching skin rash or hives swelling of the face, lips, mouth, or tongue VYXEOS contains copper and may cause copper overload in patients with Wilson's disease or other copper-processing disorders. VYXEOS can damage the skin if it leaks out of the vein. Tell your doctor right away if you experience symptoms of burning, stinging, or blisters and skin sores at the injection site. VYXEOS can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Do not breastfeed while receiving VYXEOS. Females and males of reproductive potential should use effective contraception during treatment and for 6 months following the last dose of VYXEOS. The most common side effects are bleeding events, fever, rash, swelling, nausea, sores in the mouth or throat, diarrhea, constipation, muscle pain, tiredness, stomach pain, difficulty breathing, headache, cough, decreased appetite, irregular heartbeat, pneumonia, blood infection, chills, sleep disorders, and vomiting. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit  or call 1-800-FDA-1088. You may also report side effects to Jazz Pharmaceuticals at 1-800-520-5568. About Defitelio ® (defibrotide sodium) In the U.S., Defitelio® (defibrotide sodium) injection 80mg/mL received U.S. Food and Drug Administration (FDA) marketing approval on March 30, 2016, and it is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT) and is the first and only FDA-approved therapy for patients with this rare, potentially fatal complication. Defitelio is not approved for the prevention of VOD.6 Please see full Prescribing Information for Defitelio in the United States. In Europe, defibrotide is marketed under the name Defitelio® ▼ (defibrotide). In October 2013, the European Commission granted marketing authorization to Defitelio under exceptional circumstances for the treatment of severe VOD in patients after HSCT therapy. In Europe, Defitelio is indicated in patients over one month of age. It is not indicated in patients with hypersensitivity to defibrotide or any of its excipients or with concomitant use of thrombolytic therapy. ▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system found under section 4.8 of the SmPC () The full Summary of Product Characteristics of Defitelio in Europe is available here. Important Safety Information for Defitelio Defitelio should not be given to patients who are: Currently taking anticoagulants or fibrinolytics Allergic to Defitelio or any of its ingredients Defitelio may increase the risk of bleeding in patients with VOD and should not be given to patients with active bleeding. During treatment with Defitelio, patients should be monitored for signs of bleeding. In the event that bleeding occurs during treatment with Defitelio, treatment should be temporarily or permanently stopped. Patients should tell the doctor right away about any signs or symptoms of hemorrhage such as unusual bleeding, easy bruising, blood in urine or stool, headache, confusion, slurred speech, or altered vision. Defitelio may cause allergic reactions including anaphylaxis. Patients who develop signs and symptoms of anaphylaxis such as trouble breathing, severe itching, skin rash or hives, or swelling of the face, lips, mouth or tongue should seek medical attention immediately. The most common side effects of Defitelio are decreased blood pressure, diarrhea, vomiting, nausea and nose bleeds. About Zepzelca® (lurbinectedin) Zepzelca is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and eventual cell death.4 The FDA approved Zepzelca under accelerated approval in June 2020 for the treatment of adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy. The approval is based on overall response rate (ORR) and duration of response demonstrated in an open-label, monotherapy clinical study. In December 2021, Jazz and PharmaMar announced the initiation of LAGOON, a confirmatory Phase 3 clinical trial of Zepzelca for the treatment of patients with relapsed small cell lung cancer. If positive, LAGOON could confirm the benefit of Zepzelca in the treatment of small cell lung cancer (SCLC) when patients progress following 1L treatment with a platinum-based regimen and support full approval in the U.S. Zepzelca is a prescription medicine used to treat adults with SCLC that has spread to other parts of the body (metastatic) and who have received treatment with chemotherapy that contains platinum, and it did not work or is no longer working. Zepzelca is approved based on response rate and how long the response lasted. Additional studies will further evaluate the benefit of Zepzelca for this use. Important Safety Information for ZEPZELCA Before receiving ZEPZELCA, tell your healthcare provider about all of your medical conditions, including if you: have liver or kidney problems. are pregnant or plan to become pregnant. ZEPZELCA can harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with ZEPZELCA. You should use effective birth control (contraception) during treatment with and for 6 months after your final dose of ZEPZELCA. Tell your healthcare provider right away if you become pregnant or think that you are pregnant during treatment with ZEPZELCA. Males with female partners who are able to become pregnant should use effective birth control during treatment with and for 4 months after your final dose of ZEPZELCA. Females who are breastfeeding or plan to breastfeed. It is not known if ZEPZELCA passes into your breastmilk. Do not breastfeed during treatment with ZEPZELCA and for 2 weeks after your final dose of ZEPZELCA. Talk to your healthcare provider about the best way to feed your baby during treatment with ZEPZELCA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Certain other medicines may affect how ZEPZELCA works. What should I avoid while using ZEPZELCA? Avoid eating or drinking grapefruit, or products that contain grapefruit juice during treatment with ZEPZELCA. ZEPZELCA can cause serious side effects, including: Low blood cell counts. Low blood counts including low neutrophil counts (neutropenia) and low platelet counts (thrombocytopenia) are common with ZEPZELCA, and can also be severe. Some people with low white blood cell counts may get fever, or an infection throughout the body (sepsis), that can cause death. Your healthcare provider should do blood tests before you receive each treatment with ZEPZELCA to check your blood cell counts. Tell your healthcare provider right away if you develop: fever or any other signs of infection unusual bruising or bleeding tiredness pale colored skin Liver problems. Increased liver function tests are common with ZEPZELCA, and can also be severe. Your healthcare provider should do blood tests to check your liver function before you start and during treatment with ZEPZELCA. Tell your healthcare provider right away if you develop symptoms of liver problems including: loss of appetite nausea or vomiting pain on the right side of your stomach area (abdomen) Your healthcare provider may temporarily stop treatment, lower your dose, or permanently stop ZEPZELCA if you develop low blood cell counts or liver problems during treatment with ZEPZELCA. The most common side effects of ZEPZELCA include: Tiredness low white and red blood cell counts increased kidney function blood test (creatinine) increased liver function blood tests increased blood sugar (glucose) nausea decreased appetite muscle and joint (musculoskeletal) pain low level of albumin in the blood constipation trouble breathing low levels of sodium and magnesium in the blood vomiting cough diarrhea These are not all of the possible side effects of ZEPZELCA. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. You may also report side effects to Jazz Pharmaceuticals at 1-800-520-5568. More information about Zepzelca, including Full Prescribing Information and Patient Information, is available here. ZEPZELCA is a trademark of Pharma Mar, S.A. used by Jazz Pharmaceuticals under license. About Jazz Pharmaceuticals Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases—often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in neuroscience and oncology. Within these therapeutic areas, we are identifying new options for patients by actively exploring small molecules and biologics, and through innovative delivery technologies and cannabinoid science. Jazz is headquartered in Dublin, Ireland and has employees around the globe, serving patients in nearly 75 countries. Please visit for more information. Caution Concerning Forward-Looking Statements This press release contains forward-looking statements, including, but not limited to, statements related to improving standards of care in blood cancer and other hematologic diseases and other statements that are not historical facts. These forward-looking statements are based on Jazz Pharmaceuticals' current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with pharmaceutical product development, and other risks and uncertainties affecting Jazz Pharmaceuticals and its development programs, including those described from time to time under the caption "Risk Factors" and elsewhere in Jazz Pharmaceuticals plc's Securities and Exchange Commission filings and reports (Commission File No. 001-33500), including Jazz Pharmaceuticals' Annual Report on Form 10-K for the year ended December 31, 2022, as supplemented by our Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, and future filings and reports by Jazz Pharmaceuticals. Other risks and uncertainties of which Jazz Pharmaceuticals is not currently aware may also affect Jazz Pharmaceuticals' forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. The forward-looking statements herein are made only as of the date hereof or as of the dates indicated in the forward-looking statements, even if they are subsequently made available by Jazz Pharmaceuticals on its website or otherwise. Jazz Pharmaceuticals undertakes no obligation to update or supplement any forward-looking statements to reflect actual results, new information, future events, changes in its expectations or other circumstances that exist after the date as of which the forward-looking statements were made. Contacts: Jazz Media Contact: Kristin Bhavnani Head of Strategic Brand Engagement Jazz Pharmaceuticals plc [email protected] Ireland +353 1 637 2141 U.S. +1 215 867 4948 Jazz Investor Contact: Andrea N. Flynn, Ph.D. Vice President, Head, Investor Relations Jazz Pharmaceuticals plc [email protected] Ireland +353 1 634 3211 U.S. +1 650 496 2717 References 1 Maese L, et al. Efficacy and Safety of Intramuscular (IM) Recombinant Erwinia Asparaginase in Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL): The Children's Oncology Group (COG) AALL1931 study. American Society of Hematology. 2023. Available at 2 Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 3 Vyxeos (daunorubicin and cytarabine) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 4 ZEPZELCA (lurbinectedin) Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. SOURCE Jazz Pharmaceuticals plc

Clinical ResultDrug ApprovalOrphan DrugBreakthrough TherapyPhase 2

09 May 2023

·www.biospace.com

Omeros Corporation Reports First Quarter 2023 Financial Results

– Conference Call Today at 4:30 p.m. ET – SEATTLE--(BUSINESS WIRE)-- Omeros Corporation (Nasdaq: OMER), a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders including complement-mediated diseases, cancers, and addictive and compulsive disorders, today announced recent highlights and developments as well as financial results for the first quarter ended March 31, 2023, which include: Net loss was $33.7 million in the first quarter of 2023, or $0.54 per share, compared to a net loss in the first quarter of 2022 of $33.0 million, or $0.53 per share; our first quarter’s net loss from continuing operations was $39.7 million compared to $39.5 million in the first quarter of 2022, and $0.63 per share for both periods. Cash burn for the first quarter of 2023 was $23.6 million, exclusive of a $200 million milestone payment received in the quarter, a decrease from $26.0 million in the prior quarter. In February 2023 we received from Rayner Surgical, Inc. (“Rayner”) the $200 million milestone payment due under the Asset Purchase Agreement by which we sold our former ophthalmology product OMIDRIA® to Rayner in late 2021. The payment became due upon the achievement of the milestone event in December 2022 and was recorded as a receivable in the fourth quarter of 2022. For the quarter ended March 31, 2023, we earned OMIDRIA royalties of $9.2 million on Rayner’s U.S. net sales of $30.7 million. This compares to earned royalties of $13.8 million during the first quarter of the prior year on U.S. net sales of $27.7 million. The above-referenced milestone event triggered a reduction of our U.S. base royalty rate from 50 percent to 30 percent. At March 31, 2023, we had $371.4 million of cash, cash equivalents and short-term investments available. In addition, we had $10.0 million of accounts receivable. We intend to resubmit our Biologics License Application (“BLA”) for narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy (“TA-TMA”) and, consistent with direction from FDA’s Office of New Drugs, have submitted to FDA a proposed plan for assessment of both response rate and survival based on already existing clinical trial data and external data. A meeting with the review division is scheduled for this month to discuss the details of our proposed analyses and to confirm the information required by FDA to support resubmission of the BLA for narsoplimab’s approval. In April 2023, we announced positive results from a pre-specified interim analysis of our ongoing Phase 1b clinical trial of OMS906 in treatment-naïve adults with paroxysmal nocturnal hemoglobinuria (“PNH”), and updated interim results are provided later in this release. In April 2023, we were awarded a three-year $6.69 million grant from the National Institute on Drug Abuse (“NIDA”), part of the National Institutes of Health, to develop the lead orally administered PDE7 inhibitor compound in our OMS527 program for the treatment of cocaine use disorder (“CUD”). “We are pleased with our progress during the first quarter as our team continues to deliver on important milestones,” said Gregory A. Demopulos, M.D., Omeros’ chairman and chief executive officer. “For our MASP-2 inhibitor narsoplimab, we are meeting with FDA this month to discuss our proposed analysis plan and confirm the specifics to be included in a BLA resubmission for TA-TMA, and our Phase 3 IgA nephropathy trial remains on track for data read-out next quarter. Our long-acting MASP-2 inhibitor is set to begin enrolling its multiple-ascending-dose clinical trial this summer in the U.S. Enrollment is marching ahead in our OMS906 clinical program. The results to date in treatment-naïve PNH patients are impressive, making clear that our MASP-3 inhibitor OMS906 blocks alternative pathway activation and should be effective across AP-related diseases while potentially offering significant safety, efficacy and compliance advantages over other AP-targeting drugs. Now collaborating with and having received a $6.69 million award from NIDA, we are moving forward to assess our PDE7 inhibitor OMS527 in patients with cocaine use disorder. Our immuno-oncology franchise is also rapidly progressing across both our cellular and biologic platforms. Helping to fund the ongoing achievements of these and our other programs is the non-dilutive $200 million milestone payment received in February, forecast to extend our cash runway into 2025. This year has started well for Omeros, and we expect that momentum to continue.” First Quarter and Recent Clinical Developments Recent developments regarding narsoplimab, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 (“MASP-2”) in advanced clinical programs for the treatment of TA-TMA and immunoglobulin A (“IgA”) nephropathy, include: We are preparing to meet with FDA’s Division of Nonmalignant Hematology later this month to confirm the information required by FDA to support resubmission of the BLA for narsoplimab’s approval in TA-TMA. Consistent with direction from FDA’s Office of New Drugs, provided as part of its denial of our appeal of the complete response letter previously issued by FDA, we have proposed a plan to assess already existing clinical trial data and external data on both response rate and survival. In our Phase 3 ARTEMIS-IGAN trial evaluating narsoplimab for the treatment of IgA nephropathy, we remain on track to read out 9-month data on the proteinuria endpoint next quarter. Narsoplimab is the focus of two recent peer-reviewed publications. One, in Thrombosis Journal, describes a 6-year-old girl with TA-TMA following stem cell transplantation for severe aplastic anemia who had failed treatment with defibrotide. Treated with narsoplimab under compassionate use, her TMA resolved. A recurrence of TMA triggered by parvovirus again was successfully treated with narsoplimab. A second manuscript authored by investigators at Weill Cornell Medicine is in press at Clinical and Experimental Immunology. The manuscript reports a high correlation between elevation of a biomarker of endothelial injury and TA-TMA. Using plasma samples from patients in the narsoplimab pivotal trial, the study also showed that, in those trial patients classified as “responders,” narsoplimab restored biomarker levels to those of stem-cell transplant patients without TMA while biomarker levels in narsoplimab “non-responders” remained high. The 49th annual meeting of the European Society for Blood and Marrow Transplantation (EBMT), which recently concluded in Paris, featured three presentations regarding narsoplimab in TA-TMA. The first described the design of our ongoing multi-center Phase 2 study evaluating the efficacy and safety of narsoplimab in high-risk pediatric patients with TA-TMA. The second was a case report of a patient treated with narsoplimab under our compassionate use program. The patient had worsening TA-TMA following withdrawal of calcineurin inhibitors, which resolved following narsoplimab treatment. The third was a report of five cases of high-risk pediatric TA-TMA. Three of five failed treatment with the C5 inhibitor eculizumab. Two of these three patients also failed treatment with defibrotide and were then treated with narsoplimab, provided under compassionate use. Following narsoplimab treatment, TA-TMA resolved. At the annual meeting of the American Society of Pediatric Hematology/Oncology, being held this week in Fort Worth, Texas, clinical investigators will present the course of a 3-year-old girl with relapsed high-risk neuroblastoma who developed refractory TA-TMA following a second stem cell transplant. After failing treatment with each of eculizumab and defibrotide, the patient’s TA-TMA resolved following treatment with narsoplimab. A case report on narsoplimab treatment of a patient with recurrent IgA nephropathy was featured at the recent annual meeting of the Korean Society of Nephrology. Treatment with narsoplimab stabilized both proteinuria and estimated glomerular filtration rate (“eGFR”). Kidney biopsy results confirmed the beneficial effects of narsoplimab in this patient. This was the first report of complement inhibitor treatment of a patient with recurrent IgA nephropathy. A manuscript authored by a group of international experts detailing the role of the lectin pathway in the pathophysiology of IgA nephropathy, including glomerular injury, thrombotic microangiopathy, and tubulointerstitial fibrosis, was recently accepted for publication in Kidney International. Recent developments regarding OMS1029, our long-acting, next-generation MASP-2 inhibitor, include: In April 2023, we announced results from a pre-specified interim analysis of our ongoing Phase 1b clinical trial of OMS906 in treatment-naïve adults with PNH. Updated data from this open label trial continue to show statistically significant and clinically meaningful improvements in all measured markers of hemolysis, including hemoglobin (“Hgb”) and lactate dehydrogenase (“LDH”). Despite all patients having received only the lowest of doses planned for the trial, data compare very favorably to those publicly available for marketed and in-development alternative pathway inhibitors. Enrollment is ongoing. Updated data are provided below (“n”, or the number of patients, at each time point ranges from 3 to 9 depending on each patient’s respective date of enrollment): Hemoglobin Mean baseline Hgb is 6.78 g/dL (normal: 12.0–15.6 g/dL for women, 13.5–17.2 g/dL for men) Mean absolute increase in Hgb is 3.4 g/dL at Day 29, 6.3 g/dL at Day 85, and 9.7 g/dL at Day 113 After only 1 dose (by Day 29), Hgb increased ≥ 2 g/dL in 67% of patients After only 2 doses (by Day 57), Hgb increased ≥ 2g/dL in 100% and by ≥ 4 g/dL in 80% of patients By Day 85, 67% of patients had Hgb ≥ 12 g/dL; by Day 113, 100% of patients had Hgb ≥ 15.7 g/dL Mean reduction in absolute reticulocyte counts from baseline were ≥ 70,000/µL (range 70,000 – 136,000/µL) at all time points No patients have had a clinical breakthrough or thrombotic event, and none have required a transfusion while receiving OMS906 LDH Mean baseline LDH is 1931 U/L (~8-fold higher than the upper limit of normal) Mean reduction in LDH is 83% at Day 15, 80% at Day 29, and 87% at Day 113 At Day 113, LDH for all patients is normal or < 1.5 times normal Both Hgb and LDH improvements are statistically significant at all time points in the trial; OMS906 has been well tolerated and there have been no safety signals of concern. Based on PK/PD data from a successful Phase 1 single-ascending-dose study of OMS906 in healthy subjects and the interim data from our Phase 1b clinical trial in treatment-naïve PNH patients, we are planning a dosing frequency of once quarterly, either intravenously or subcutaneously. We are also enrolling a Phase 1b clinical trial evaluating OMS906 in PNH patients who have had an unsatisfactory response to the C5 inhibitor ravulizumab. This study has a “switch-over” design and enrolls PNH patients receiving ravulizumab, adds OMS906 to provide combination therapy with ravulizumab for 24 weeks, and then provides OMS906 monotherapy in patients who demonstrate a hemoglobin response with combination therapy. Patient treatment with OMS906 is underway. A Phase 1b clinical program evaluating OMS906 in patients with complement 3 glomerulopathy (“C3G”) is also ongoing. Additional updates on data from our three OMS906 trials in progress are planned for the second half of this year. The Annual Meeting of the European Hematology Association to be held this June in Frankfurt, Germany, will feature a presentation on the study design of our two ongoing clinical trials of OMS906 in patients with PNH, along with results from our single-ascending-dose Phase 1 study evaluating both intravenous and subcutaneous administration of OMS906 in healthy subjects. Recent developments regarding OMS527, our phosphodiesterase 7 (“PDE7”) inhibitor program focused on addiction and movement disorders, include: In April 2023, we were awarded a grant from the National Institute on Drug Abuse, part of the National Institutes of Health to develop our lead orally administered PDE7 inhibitor compound for the treatment of cocaine use disorder (“CUD”). The grant – $6.69 million over three years – is intended to support a preclinical cocaine interaction study and a randomized, placebo-controlled, inpatient clinical study evaluating the safety and effectiveness of OMS527 in patients with CUD. A Phase 1 clinical trial of the study drug in healthy subjects was successfully completed. OMS527 is also being evaluated by investigators at Emory University as a potential treatment for levodopa-induced dyskinesias (“LID”), which are crippling, involuntary movements reportedly affecting 50 percent or more of levodopa-treated patients with Parkinson’s disease. LID is caused by prolonged treatment with levodopa, the most prescribed treatment for the over 10 million patients with Parkinson’s disease worldwide. Data on OMS527 in LID will be publicly disclosed following the filing of appropriate patent applications. Financial Results Net loss for the first quarter of 2023 was $33.7 million, or $0.54 per share. This compares to a net loss in the first quarter of 2022 of $33.0 million, or $0.53 per share. Net loss from continuing operations for the first quarter of 2023 was $39.7 million compared to $39.5 million in the first quarter of 2022, and $0.63 per share for both periods. Cash burn for the first quarter of 2023 was $23.6 million, exclusive of the $200 million milestone payment from Rayner, compared to $26.0 million in the fourth quarter of 2022. During the first quarter of 2023, we earned royalties of $9.2 million on $30.7 million of Rayner’s U.S. net sales of OMIDRIA. This compares to earned royalties of $13.8 million during the first quarter of the prior year on U.S. net sales of $27.7 million. These royalties were recorded as a reduction of the OMIDRIA contract royalty asset. Omeros received a $200 million milestone payment from Rayner in the first quarter of 2023 in connection with the Asset Purchase Agreement under which Rayner purchased our OMIDRIA business. The achievement of the milestone event in late December 2022 triggered a reduction of our U.S. base royalty rate from 50 percent to 30 percent. Total costs and expenses for the first quarter of 2023 were $35.7 million compared to $35.0 million for the first quarter of 2022. Interest expense during the first quarter of 2023 was $7.9 million compared to $4.9 million during the first quarter of 2022. The increase was due to interest on our OMIDRIA contract royalty obligation associated with the sale of a portion of our OMIDRIA royalty receivables, which we entered into during the third quarter of 2022. During the first quarter of 2023, we earned $4.0 million in interest and other income compared to $0.5 million in the prior year quarter. The increase was due to higher average balances available to invest and higher market interest rates in the current year quarter. Net income from discontinued operations, net of tax was $6.0 million, or $0.09 per share, in the first quarter of 2023 compared to $6.5 million, or $0.10 per share, in the first quarter of 2022. As of March 31, 2023, we had $371.4 million of cash and short-term investments, all of which are held in our name, available for operations and debt service. In addition, we had $10.0 million in accounts receivable. Our cash provided by operations during the first quarter of 2023 was $174.5 million and included the $200.0 million collection of the Rayner milestone payment. Conference Call Details To access the live conference call via phone, please dial (800) 715-9871 from the United States and Canada or (646) 307-1963 internationally and ask to be placed into the Omeros earnings call. Please dial in approximately 10 minutes prior to the start of the call. A telephone replay will be available for one week following the call and may be accessed by dialing (800) 770-2030 from the United States or Canada or (609) 800-9909 internationally. The replay access code is 8266699. For online access to the live or subsequently archived webcast of the conference call, go to Omeros’ website at . About Omeros Corporation Omeros is an innovative biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders including complement-mediated diseases, cancers, and addictive and compulsive disorders. Omeros’ lead MASP-2 inhibitor narsoplimab targets the lectin pathway of complement and is the subject of a biologics license application pending before FDA for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA). Narsoplimab is also in multiple late-stage clinical development programs focused on other complement-mediated disorders, including IgA nephropathy, COVID-19, and atypical hemolytic uremic syndrome. Omeros’ long-acting MASP-2 inhibitor OMS1029 is currently in a Phase 1 clinical trial. OMS906, Omeros’ inhibitor of MASP-3, the key activator of the alternative pathway of complement, is advancing across multiple clinical programs for alternative pathway-related diseases, including paroxysmal nocturnal hemoglobinuria (PNH) and complement 3 (C3) glomerulopathy. For more information about Omeros and its programs, visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, which are subject to the “safe harbor” created by those sections for such statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “goal,” “intend,” “likely,” “look forward to,” “may,” “objective,” “plan,” “potential,” “predict,” “project,” “should,” “slate,” “target,” “will,” “would” and similar expressions and variations thereof. Forward-looking statements, including statements regarding prospects for obtaining FDA approval of narsoplimab in TA-TMA and anticipated next steps in relation to the biologics license application for narsoplimab, expectations regarding the initiation or continuation of clinical trials evaluating Omeros’ drug candidates and the anticipated availability of data therefrom, and expectations regarding growth in royalty-generating sales of OMIDRIA, are based on management’s beliefs and assumptions and on information available to management only as of the date of this press release. Omeros’ actual results could differ materially from those anticipated in these forward-looking statements for many reasons, including, without limitation, unanticipated or unexpected outcomes of regulatory processes in relevant jurisdictions, unproven preclinical and clinical development activities, financial condition and results of operations, regulatory processes and oversight, challenges associated with manufacture or supply of our investigational or clinical products, changes in reimbursement and payment policies by government and commercial payers or the application of such policies, intellectual property claims, competitive developments, litigation, and the risks, uncertainties and other factors described under the heading “Risk Factors” in the company’s Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 13, 2023. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and the company assumes no obligation to update these forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. OMEROS CORPORATION UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (In thousands, except share and per share data) Three Months Ended March 31, 2023 2022 Costs and expenses: Research and development $ 24,610 $ 24,087 Selling, general and administrative 11,103 10,959 Total costs and expenses 35,713 35,046 Loss from continuing operations (35,713 ) (35,046 ) Interest expense (7,933 ) (4,941 ) Interest and other income 3,963 493 Net loss from continuing operations (39,683 ) (39,494 ) Net income from discontinued operations, net of tax 5,982 6,483 Net loss $ (33,701 ) $ (33,011 ) Basic and diluted net income (loss) per share Net loss from continuing operations $ (0.63 ) $ (0.63 ) Net income from discontinued operations 0.09 0.10 Net loss $ (0.54 ) $ (0.53 ) Weighted-average shares used to compute basic and diluted net income (loss) per share 62,828,765 62,724,775 OMEROS CORPORATION UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEET (In thousands) March 31, December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $ 3,829 $ 11,009 Short-term investments 367,527 183,909 OMIDRIA contract royalty asset, short-term 28,940 28,797 Receivables 10,033 213,221 Prepaid expense and other assets 6,708 6,300 Total current assets 417,037 443,236 OMIDRIA contract royalty asset 119,681 123,425 Right of use assets 21,025 21,762 Property and equipment, net 1,335 1,492 Restricted investments 1,054 1,054 Total assets $ 560,132 $ 590,969 Liabilities and shareholders’ equity Current liabilities: Accounts payable $ 6,446 $ 5,989 Accrued expenses 30,821 30,551 Current portion of unsecured convertible senior notes, net 94,554 94,381 Current portion of OMIDRIA royalty obligation 2,943 1,152 Current portion of lease liabilities 4,427 4,310 Total current liabilities 139,191 136,383 Unsecured convertible senior notes, net 221,209 220,906 OMIDRIA royalty obligation 123,057 125,126 Lease liabilities, non-current 21,287 22,426 Other accrued liabilities, non-current 452 444 Shareholders’ equity: Common stock and additional paid-in capital 724,354 721,401 Accumulated deficit (669,418 ) (635,717 ) Total shareholders’ equity 54,936 85,684 Total liabilities and shareholders’ equity $ 560,132 $ 590,969

Phase 1Clinical ResultPhase 2Phase 3Financial Statement

100 Deals associated with Defibrotide Sodium

External Link

KEGG	Wiki	ATC	Drug Bank
D07423	Defibrotide Sodium	B01AX01	DB04932

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Venoocclusive disease	CA	Jazz Pharmaceuticals Plc	06 Sep 2017
Hepatic Veno-Occlusive Disease	EU	Gentium Srl	18 Oct 2013
Hepatic Veno-Occlusive Disease	IS	Gentium Srl	18 Oct 2013
Hepatic Veno-Occlusive Disease	LI	Gentium Srl	18 Oct 2013
Hepatic Veno-Occlusive Disease	NO	Gentium Srl	18 Oct 2013

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
High Risk Neuroblastoma	Phase 2	US	Jazz Pharmaceuticals, Inc.	01 Jun 2024
Thrombotic Microangiopathies	Phase 2	US	Jazz Pharmaceuticals, Inc.	01 Jun 2024
COVID-19	Phase 2	US	Jazz Pharmaceuticals Plc	01 Jan 2021
Diffuse large B-cell lymphoma recurrent	Phase 2	US	Jazz Pharmaceuticals Plc	04 Oct 2019
Neurotoxicity Syndromes	Phase 2	US	Jazz Pharmaceuticals Plc	04 Oct 2019
Acute Graft Versus Host Disease	Phase 2	US	Jazz Pharmaceuticals Plc	21 Feb 2018
Acute Graft Versus Host Disease	Phase 2	AT	Jazz Pharmaceuticals Plc	21 Feb 2018
Acute Graft Versus Host Disease	Phase 2	BE	Jazz Pharmaceuticals Plc	21 Feb 2018
Acute Graft Versus Host Disease	Phase 2	BG	Jazz Pharmaceuticals Plc	21 Feb 2018
Acute Graft Versus Host Disease	Phase 2	CA	Jazz Pharmaceuticals Plc	21 Feb 2018

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04530604 (CTgov)	Phase 1	COVID-19 \| Respiratory Distress Syndrome, Adult	13	Defibrotide	fzzdpkdaxo(oecfawatan) = kjwkptxhwo dlxhxreumz (uzwoqcphmf, vdjgmlpodp - vfcydrtfrv) View more	-	09 May 2023
P518 (EBMT2023)	Not Applicable	Hematopoietic stem cell transplantation	91	Defibrotide	rqacaghfre(etkkjhfizt) = mgawfoeomr mulklzdgnc (qdkfaxgqzh )	-	23 Apr 2023
P549 (EBMT2023)	Not Applicable	Hepatic Veno-Occlusive Disease	151	DEFIBROTIDE	uvhxrmdhia(cptkenkkkz) = pmhnpuhuko mhrnzumlgo (pbfbhiglfr )	-	23 Apr 2023
DEFIFrance (EBMT2023)	Not Applicable	Hepatic Veno-Occlusive Disease	226	DEFIBROTIDE	bdyozjslfr(qbovuvrcga) = pvebefhqxz ipnjhlgzhh (ojamrhkell, 53.2% - 68.0%) View more	-	23 Apr 2023
DEFIFrance (EBMT2023)	Not Applicable	Hepatic Veno-Occlusive Disease	226	DEFIBROTIDE	bdyozjslfr(qbovuvrcga) = fzrqbxqxdv ipnjhlgzhh (ojamrhkell, 31.2% - 56.2%) View more	-	23 Apr 2023
P539 (EBMT2023)	Not Applicable	Hepatic Veno-Occlusive Disease	241	Low dose defibrotide	xwmfzrenru(yrpklagcfi) = odalzbgiqh kwqvhklkwk (zuesiqujda )	Positive	23 Apr 2023
Pubmed	Phase 2	Acute Graft Versus Host Disease	-	Defibrotide prophylaxis arm	axmjfwhqfe(hpkjtflsfk) = rsqrqxlomc giaymznqvm (vunfwwsqrh )	-	15 Dec 2022
Pubmed	Phase 2	Acute Graft Versus Host Disease	-	defibrotide (SOC arm)	axmjfwhqfe(hpkjtflsfk) = ioaokpgnic giaymznqvm (vunfwwsqrh )	-	15 Dec 2022
EHA2022	Not Applicable	Hepatic Veno-Occlusive Disease \| Venoocclusive disease	249	Defibrotide-treated adult patients	pmjqewnunr(cvvjiiqnwa) = gteavrwwcq rjpfwekjga (qjhmdknisc, 49%, 87%)	-	12 May 2022
DEFIFrance (EBMT2022)	Not Applicable	Hepatic Veno-Occlusive Disease	336	defibrotide	bhbtjbutpt(efuespljhg) = mild/moderate VOD/SOS: 11% [standard onset]; 36% [late onset]; severe/very severe: 13% [standard onset]; 25% [late onset] sbmkrtppsy (rohrmprlrh ) View more	-	19 Mar 2022
DEFIFrance (EBMT2022)	Not Applicable	Hepatic Veno-Occlusive Disease	336	defibrotide		-	19 Mar 2022
P460 (EBMT2022)	Not Applicable	Hematopoietic stem cell transplantation	10	Defibrotide	tbsraumowe(lqmjlehpln) = gzxkphuoft muyvblhsgp (eiktchnbsg ) View more	-	19 Mar 2022
P439 (EBMT2022)	Not Applicable	Hepatic Veno-Occlusive Disease	46	Defibrotide	iaygmeqyru(rrggyauhsb) = aiqxsjtaju wgviqgaxiz (lhdamertga ) View more	-	19 Mar 2022

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Defibrotide Sodium

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Translational Medicine

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