Thromboinflammation

Feb. 03, 2025 Aplagon, a clinical stage biopharmaceutical company developing a first-in-class therapeutic for thrombo-inflammatory diseases, known as APAC, a heparin proteoglycan mimetic with antiplatelet and anticoagulant effects, announced today it has closed a EUR 7 million financing. The funding round was led by new investors Fåhraeus Startup and Growth AB (FSG), a Nordic venture capital fund, and European Innovation Council (EIC) Fund. FSG and EIC Fund were joined by leading Finnish investors, including Jenny and Antti Wihuri Foundation, Innovestor and Gösta Serlachius Fine Arts Foundation. By mimicking naturally occurring mast cell-derived heparin proteoglycans, APAC targets arterial injury sites providing long-lasting antithrombotic and anti-inflammatory action in situ. The funding will support the initiation of Phase 2a clinical trial of APAC for peripheral arterial occlusive disease/chronic limb threatening ischemia (PAOD/CLTI) in Finland. APAC is also poised to complete three ongoing clinical trials; a Phase I clinical trial for Arteriovenous Fistula (AVF) maturation failure, a Phase I intravenous (IV) clinical trial in healthy participants, and a PET-imaging clinical trial with 89zirconium-labeled APAC in PAOD patients and healthy participants in 2025. See our recent clinical trial updates release here. APAC is intended for in-hospital use and can be administered either locally or by IV infusion. Over 40 participants have so far received APAC without any safety concerns and initial clinical findings are encouraging. Aki Prihti, CEO at Aplagon, said, “We’re delighted to secure this fund-raising, and to bring on board FSG and EIC Fund as highly experienced VC investors from outside Finland. We have been making strong progress, and this financing enables us to complete the three international clinical trials we have been running with APAC, and to start a Phase 2a study in PAOD/CLTI. Our innovative approach, using a heparin proteoglycan mimetic with targeting ability and retention on the vascular injury sites, has potential applications across a broad range of serious vascular diseases. We are looking forward to announcing clinical results from these trials in 2025 and 2026.” Johanna Asklin, General Partner at FSG, said, “Thrombo-inflammation is a key underlying driver for many cardiovascular diseases. At FSG we look for revolutionary innovations, and we found precisely that with Aplagon’s APAC approach to treat this clear unmet medical need.” Aplagon is a clinical stage biopharmaceutical company developing a first-in-class therapeutic APAC for treating thrombo-inflammatory diseases. The company’s first two lead indications are 1) the prevention of AVF maturation failure, to enable lifesaving haemodialysis treatment in end-stage kidney disease patients, and 2) CLTI, to prevent amputations and other major cardiovascular events in CLTI patients. APAC is based on the pioneering research on mast cell-derived heparin proteoglycans performed by Prof. Riitta Lassila and associates at Wihuri Research Institute in Helsinki, Finland. Aplagon is backed by a syndicate of leading Nordic investors including FSG Fund, Wihuri Foundation, Innovestor and Serlachius Foundation as well as EIC Fund. The company is headquartered in Helsinki, Finland. Fåhraeus Startup & Growth (FSG) specializes in venture capital investments within the Life Science and technology sectors, primarily focusing on the Nordics. We are drawn to companies showcasing revolutionary innovations, substantial revenue growth potential, and a demonstrated product-market fit. Established by seasoned life science and tech professionals, FSG Fund II combines deep industry insights with significant investment expertise. We pride ourselves on being hands-on owners, leveraging our expansive industry network to bolster the growth of our portfolio companies. At the helm of FSG Fund II are Managing Director Linus Wiebe, and General Partners Christer Fåhraeus and Johanna Asklin. As per the regulatory framework, FSG Fund II AB is a registered alternative investment fund under the Swedish Alternative Investment Funds Managers Act. The European Innovation Council Fund from the European Commission is an agnostic Fund: it invests across all technologies and verticals, and all EU countries and countries associated to Horizon Europe. It provides the investment component of the EIC Accelerator blended finance. The European Investment Bank acts as investment adviser to the EIC Fund. The EIC Fund aims to fill a critical financing gap and its main purpose is to support companies in the development and commercialisation of disruptive technologies, bridging with and crowding in market players, and further sharing risk by building a large network of capital providers and strategic partners suitable for co-investments and follow-on funding. The Fund pays particular attention to the empowerment and support of female founders as well as the ambition to reduce the innovation divide among EU countries. The content above comes from the network. if any infringement, please contact us to modify.

First patient enrolled in NIH/NHLBI-sponsored Phase 1 Study of fostamatinib, Rigel's oral SYK inhibitor SOUTH SAN FRANCISCO, Calif., Jan. 22, 2025 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced the first patient has been enrolled in a Phase 1 study evaluating the safety and tolerability of escalating doses of fostamatinib, the company's oral spleen tyrosine kinase (SYK) inhibitor, in patients with sickle cell disease (SCD). The study is being sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institute of Health (NIH). Fostamatinib, marketed in the U.S. as TAVALISSE® (fostamatinib disodium hexahydrate) tablets, is approved for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. "Our Phase 1 study evaluating fostamatinib in patients with sickle cell disease is an opportunity to explore a potential new treatment option for a disease that is associated with a high degree of recurrent acute pain events and other acute and chronic potentially life-threatening complications," stated Richard Childs, M.D., scientific director of the NHLBI. "Preclinical research conducted by NIH/NHLBI investigators lead us to believe that SYK inhibition may have the potential to reduce complications related to red cell sickling and thrombo-inflammation in this patient population." "We are excited to support another important study conducted by the NIH/NHLBI for fostamatinib, as they investigate SYK inhibition and its potential to benefit patients with sickle cell disease, a devasting, lifelong condition," said Raul Rodriguez, Rigel's president and CEO. "The study focuses on an area of critical unmet need and contributes to Rigel's mission to improve the lives of patients with hematologic disorders and cancer." This open label Phase 1 dose-escalation study is expected to enroll approximately 20 patients with SCD (NCT05904093). The trial is led by principal investigator Swee Lay Thein, M.D., senior investigator and chief of the Sickle Cell Branch at the NHLBI. Patients will receive oral fostamatinib at a dose of 100 mg twice daily for 14 days, which will be escalated to 150 mg twice daily for an additional 28 days if tolerated. The primary objective of the study is to evaluate the safety and tolerability of fostamatinib. The secondary and exploratory objectives are to assess the mechanism of action of fostamatinib in SCD and mechanistic effects of fostamatinib mediated SYK inhibition on red blood cell membrane integrity and deformability, rate of sickling kinetics, platelet activation and aggregation, and neutrophil activation and neutrophil extracellular trap (NET) formation. The clinical study is being conducted at the NIH Clinical Center in Bethesda, Maryland and is being funded and sponsored by the NIH/NHLBI, with study material provided by Rigel. About SCD & SYK Inhibition Sickle cell disease (SCD) is a genetic hemoglobinopathy that leads to the production of abnormal hemoglobin, the protein that carries oxygen through the body. Normally, red blood cells are disc-shaped and flexible enough to move easily through the blood vessels. In sickle cell disease, red blood cells become rigid and crescent – or "sickle" – shaped, leading to strokes, infections, vaso-occlusive crises (VOC), and multi-organ dysfunction. The condition affects more than 100,000 people in the United States1 and an estimated 7-8 million people worldwide.2 In preclinical studies, R406, the active metabolite of fostamatinib, was shown to inhibit production of neutrophil extracellular traps (NETs) by neutrophils in vitro.3 In a humanized SCD mouse model, R406 treatment significantly decreased platelet ATP secretion and aggregation in response to collagen without a significant effect on bleeding time.4 Fostamatinib could potentially ameliorate SCD-related prothrombic state without an increase in bleeding, addressing an important unmet need. Furthermore, tyrosine phosphorylation of red blood cell (RBC) Band 3 (the anion exchanger 1, of the SLC4A1 gene) compromises the RBC's integrity, leading to shedding of red cell derived microparticles and release of hemoglobin and mitochondrial DNA, key contributors to thrombo-inflammation pathophysiology. By impacting phosphorylation of RBC Band 3 protein, fostamatinib offers the potential for enhanced RBC membrane stability and reduced sickling of RBCs.5 About TAVALISSE® Indication TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Important Safety Information Warnings and Precautions Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required. Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation. Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE. Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation. TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose. Drug Interactions Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose. It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406. Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug. Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug. Adverse Reactions Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%). Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Please see www.TAVALISSEUSPI.com for Full Prescribing Information. To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088). TAVALISSE is a registered trademark of Rigel Pharmaceuticals, Inc. Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit www.rigel.com. Forward Looking Statements This press release contains forward-looking statements relating to, among other things, evaluating fostamatinib in patients with sickle cell disease and the potential of SYK inhibition to reduce complications related to red cell sickling and thrombo-inflammation. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "explore", "potential", "may", "expected", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. 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 the development and commercialization of fostamatinib; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 ir@rigel.com Media: David Rosen Argot Partners 646.461.6387 david.rosen@argotpartners.com View original content to download multimedia:https://www.prnewswire.com/news-releases/rigels-fostamatinib-being-studied-by-national-institute-of-health-in-patients-with-sickle-cell-disease-302356919.html SOURCE Rigel Pharmaceuticals, Inc.

Company’s heparin proteoglycan mimetic now in three clinical trials HELSINKI, October 24, 2024. Aplagon Oy (Aplagon), a clinical stage biopharmaceutical company developing a first-in-class therapeutic (APAC, a heparin proteoglycan mimetic) for thrombo-inflammatory diseases, announced today the first patient had been administered radiolabeled APAC and all three positron emission tomography / computed tomography (PET/CT) imaging sessions have been completed in an open-label PET-imaging study (CHASE-study). The CHASE-study investigates safety, tolerability, and biodistribution of 89zirconium-labeled APAC in six patients with peripheral arterial occlusive disease / critical limb ischemia (PAOD/CLI) and four healthy volunteers. APAC uniquely combines short systemic half-life and local, long-term effect at the vascular injury sites. The 89Zr-APAC was administered as an intravenous (IV) injection (Day 1), and PET/CT scanning performed on Day 1, Day 3, and Day 7, with the aim to determine 89Zr-APAC’s biodistribution and binding to arteries and atherosclerotic lesions. The study, performed in the Netherlands, will provide valuable information on both systemic and local pharmacokinetics of a low APAC dose after IV-administration. The CHASE-study is supported by a EUR 2.1 million EIC Accelerator grant. The EIC Accelerator APAC-ON project is focused on early clinical studies of APAC in advanced PAOD/CLI patients in Europe. Aplagon has two clinical studies ongoing besides the CHASE-study, both sponsored by Aplagon’s long-term partner, Cadila Pharmaceuticals Ltd: The Phase 1 AVF clinical study evaluates the safety and tolerability of three doses of APAC in three 10 patient cohorts of chronic kidney disease patients undergoing vascular surgery to create a radio-cephalic (wrist-area) arteriovenous fistula (AVF) to facilitate hemodialysis. In the study, APAC is administered locally inside the AVF vascular access during the surgical procedure. The Phase 1 safety study is an open label, safety, tolerability and pharmacodynamic, clinical study of single and multiple IVdoses of APAC in 40 healthy subjects. More than 40 participants have received APAC. There have been no safety concerns to date and the initial clinical findings are encouraging. Aplagon’s proprietary investigational drug, APAC, a heparin proteoglycan mimetic, is a dual AntiPlatelet and AntiCoagulant (APAC) with unique multifunctional antithrombotic and anti-inflammatory properties. APAC specifically targets arterial injury sites and acts locally at these sites to inhibit thrombosis (blood coagulation or clot formation) and inflammation. Thrombo-inflammation – the dysregulated interaction between blood and vessel wall involving platelets, coagulation processes and inflammation at the vascular injury sites – is a key underlying driver in many vascular diseases, leading to impaired blood circulation and organ damage. APAC is intended for in-hospital use and can be administered either locally (AVF) or by IV infusion (PAOD/CLI). – Ends – About Aplagon Oy (https://aplagon.com) Aplagon is a clinical stage biopharmaceutical company developing a first-in-class therapeutic APAC for treating thrombo-inflammatory diseases. The company’s first two lead indications are 1) the prevention of AVF maturation failure, to enable life-saving hemodialysis treatment in end-stage kidney disease patients, and 2) CLI, to prevent amputations and other major cardiovascular events in CLI patients. APAC is based on the pioneering research performed by Prof. Riitta Lassila and associates at Wihuri Research Institute in Helsinki, Finland on mast cell-derived heparin proteoglycans. About the European Innovation Council The European Innovation Council (EIC) is Europe’s flagship innovation programme to identity, develop and scale up breakthrough technologies and game changing innovations. The EIC has been established under the EU Horizon Europe programme. It has a budget of €10.1 billion to support game changing innovations throughout the lifecycle from early stage research, to proof of concept, technology transfer, and the financing and scale up of start-ups and SMEs. The EIC Accelerator programme supports individual Small and Medium Enterprises (SMEs), in particular startups and spinout companies to develop and scale up game-changing innovations. For further information, please contact Aki Prihti, CEO (aki.prihti@aplagon.com) or visit www.aplagon.com.