Thromboinflammation

Gosselies (Belgium), May 16, 2024 – Bioxodes SA, a clinical stage biopharmaceutical company developing novel therapies for the prevention and treatment of thrombotic and inflammatory diseases, announces today it has received a notice from the European Patent Office of its intention to grant a patent for the lead asset of Bioxodes, BIOX-101 (Ir-CPI), further broadening the candidate therapy’s protection in thromboinflammation, and adding to the company’s strong portfolio of intellectual property rights, which include a related approval in Australia, dating from June 2022, and a pending patent grant from Russia’s Center for Intellectual Property Rights. “The European Patent Office's intention to grant a patent for BIOX-101 in Europe represents a significant milestone for the advancement of this first-in-class drug, offering a breakthrough hope for hemorrhagic stroke patients, and demonstrating potential applicability across related conditions. The European Patent Office plays a leading role in how patent decisions are taken across the world, and we anticipate favorable outcomes for our patent filings in other countries as well,” said Marc Dechamps, Chief Executive Officer of Bioxodes. BIOX-101 has enjoyed patent protection in the US and Europe for several years for its active ingredient and for the treatment of thrombosis. The active ingredient in BIOX-101 is derived from a protein found in tick saliva, effectively preventing blood clot formation without increasing bleeding risks. By inhibiting the activation of neutrophils, it also prevents the acute neuroinflammatory events associated with intracerebral hemorrhage. BIOX-101 is in development for the treatment of patients within the first 72 hours of a hemorrhagic stroke and is currently in Phase 2a clinical testing in a randomized open-label proof-of-concept study among 32 patients in Belgium. About Bioxodes Bioxodes is a clinical stage biopharmaceutical company developing novel therapies for the prevention and treatment of thrombotic and inflammatory diseases. Since its founding in 2013, Bioxodes has developed its lead asset BIOX-101, a first-in-class drug candidate aimed at patients with thromboinflammatory disease. BIOX-101’s unique mechanism of action is the foundation of an innovative pipeline of drug candidates for the prevention of (thrombo)inflammatory diseases. The company, which is based in Gosselies in Belgium, has so far secured €34 million in funding from Belgian investment funds and business angels, including €12 million in non-dilutive funding from the Wallonia region. Worldwide, Bioxodes holds both granted and pending patents associated with Ir-CPI. For more information please contact: HEAD OFFICES Parc d’activités Aéropole Rue Santos-Dumont, 1 6041 Gosselies, Belgium +32 496 590354 investment@bioxodes.com MEDIA RELATIONS Alexandra Schiettekatte alexandra.alicato@outlook.com +32 476 65 04 38 COHESION BUREAU EU MEDIA RELATIONS Sophie Baumont sophie.baumont@cohesionbureau.com INVESTOR RELATIONS Giovanni Ca’ Zorzi giovanni.cazorzi@cohesionbureau.com Attachment 20240516_Bioxodes_PR_patents_FINAL_EN

-- Provides Update on ACTIV-4 Host Tissue Trial -- SOUTH SAN FRANCISCO, Calif., Oct. 11, 2023 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced an upcoming oral presentation highlighting data from the FOCUS Phase 3 clinical trial of fostamatinib in hospitalized COVID-19 patients without respiratory failure who have certain high-risk prognostic factors at IDWeek 2023 being held October 11-15, 2023, in Boston, MA and provided an update on the ACTIV-4 Host Tissue trial of fostamatinib in hospitalized patients with COVID-19. "From the outset of the COVID-19 pandemic, we were hopeful of making an impact. However, our focus remains on our hematology-oncology commercial and clinical portfolio," said Raul Rodriguez, Rigel's president and CEO. "As we have previously reported, we do not plan to submit an Emergency Use Authorization or a supplemental New Drug Application given the end of the federal COVID-19 Public Health Emergency in May 2023, and based on feedback from the FDA, US Department of Defense and other advisors regarding the program's regulatory requirements, costs, timeline and potential for success." Details of the oral presentation at IDWeek 2023 are as follows: Abstract #: 88 Title: Fostamatinib for the Treatment of Hospitalized Patients With COVID-19 Who Required Oxygen Supplementation: Results of a Phase 3 Trial Presenter: Dr. Deepa Gotur, MD, FCCP, FCCM, Associate Professor Clinical Medicine, Weill Cornell Medical College and Houston Methodist Hospital, Houston, TX Session Name: Clinical Trials Date: Thursday, October 12, 2023 Presentation Time: 11:15 – 11:30AM ET Location: 102 AB, Boston Convention and Exhibition Center This presentation reports severe COVID-19 is linked to hyperactivation of the host immune response involving signaling through multiple spleen tyrosine kinase (SYK) pathways. Fostamatinib is an orally administered potent and selective inhibitor of SYK that has been approved in the US, Canada, Japan, and Europe for the treatment of chronic immune thrombocytopenia (ITP). The FOCUS Phase 3 clinical trial was a double-blind, randomized, placebo-controlled trial of fostamatinib in adults hospitalized for COVID-19 who required oxygen supplementation (NCT04629703). Patients were randomly assigned 1:1 to receive fostamatinib (150 mg BID administered orally) or placebo for 14 days. All patients additionally received standard of care at their hospital. The primary endpoint was days on oxygen (days 1-29). A total of 280 patients underwent randomization (with 141 assigned to fostamatinib and 139 to placebo). The primary endpoint was met; those who received fostamatinib had lower mean days on oxygen than those who received placebo (4.8 vs. 7.6 days, p=0.0136). Fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo. The mean change in the 8-point ordinal score from baseline to the average of Day 5 to 15 was significantly improved in patients who received fostamatinib vs. placebo (p=0.0092). Furthermore, 6 patients were enrolled with baseline ordinal score of 6 (3 in each group). All patients in the fostamatinib group survived, and all in the placebo group died by Day 30. A significantly higher proportion of patients who received fostamatinib were discharged from the hospital by Day 15 compared to placebo (p=0.0029). Significantly more patients were alive and oxygen-free by Day 29 and Day 60 with fostamatinib treatment in comparison to placebo (p=0.0213 and p=0.0271, respectively). Treatment-emergent adverse events were consistent with previous studies and were similar between the 2 groups. The addition of fostamatinib to standard of care treatment resulted in significantly fewer days on oxygen, an improved 8-point ordinal scale score, and significantly more patients alive and oxygen-free by Day 60 compared to placebo in patients with COVID-19 requiring hospitalization and supplemental oxygen. ACTIV-4 Host Tissue (NECTAR) Trial Update On September 26, 2023, the Data and Safety Monitoring Board (DSMB) recommended that the fostamatinib study arm of the ACTIV-4 Host Tissue (NECTAR) platform cease enrollment. Based on their review of a conditional power analysis, the DSMB determined that there was an extremely low likelihood of fostamatinib providing benefits related to the primary outcome (Oxygen Free Days) or other secondary outcomes in patients hospitalized and on oxygen therapy for COVID-19. No safety concerns were identified. The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, concurs with the DSMB's recommendations and has asked the trial investigators to cease enrollment, complete follow-up for participants already enrolled, and complete study closeout. The full study data will be analyzed and disseminated as previously planned. About COVID-19 & SYK Inhibition COVID-19 is the infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 primarily infects the upper and lower respiratory tract and can lead to acute respiratory distress syndrome (ARDS). Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock resulting in endothelial dysfunction and subsequently micro and macrovascular thrombosis.1 Much of the underlying pathology of SARS-CoV-2 is thought to be secondary to a hyperinflammatory immune response associated with increased risk of thrombosis.2 SYK is involved in the intracellular signaling pathways of many different immune cells. Therefore, SYK inhibition may improve outcomes in patients with COVID-19 via inhibition of key Fc gamma receptor (FcγR) and c-type lectin receptor (CLR) mediated drivers of pathology such as pro-inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps (NETs) by neutrophils, and platelet aggregation.3,4,5,6 Furthermore, SYK inhibition in neutrophils and platelets may lead to decreased thrombo-inflammation, alleviating organ dysfunction in critically ill patients with COVID-19. 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 . Berlin DA, Gulick RM, and Martinez FJ. Severe Covid-19. N Engl J Med 2020. DOI: Becker RC. COVID-19 Update: COVID-19 associated coagulopathy. Journal of Thrombosis and Thrombolysis May 15, 2020. DOI: Hoepel W et al. High titers and low fucosylation of early human anti–SARS-CoV-2 IgG promote inflammation by alveolar macrophages. Science Translational Medicine 02 Jun 2021. DOI: Sung P-S and Hsieh S-L. CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections. Frontiers in Immunology December 6, 2019. DOI: Bye AP et al. Aberrant glycosylation of anti-SARS-CoV-2 IgG is a pro-thrombotic stimulus for platelets. BioRxiv March 26, 2021. DOI: Strich J et al. Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic. Journal of Infectious Disease March 15, 2021. DOI: Forward-Looking Statements This release contains forward-looking statements relating to, among other things, our expectations related to the role of fostamatinib in the treatment of patients with COVID-19 and in future pandemics, including next steps in collaboration with Rigel's partner, the U.S. Department of Defense, and the timing and results of the ACTIV-4 study. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "potential", "may", "expects", and similar expressions are intended to identify these forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions, 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 detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended June 30, 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 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. Investors & Media Contacts: Investors: Rigel Pharmaceuticals, Inc.  650.624.1232 ir@rigel.com Media: David Rosen Argot Partners Phone: 212.600.1902 Email: david.rosen@argotpartners.com Company Codes: NASDAQ-NMS:RIGL

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Science2Startup (S2S) ™ , an invitation-only symposium presented by Atlas Venture , F-Prime Capital , Osage University Partners , RA Capital Management , 5AM Ventures and Massachusetts Biotechnology Council (MassBio) that aims to strengthen connections between therapeutics researchers at the world’s top academic research institutions and biotech investors, will be held May 3, 2023 at the Broad Institute in Cambridge, Massachusetts. S2S is returning for the first time since 2019, with a focus on bringing academic innovations in the therapeutics space to the attention of the thriving Boston-based venture capital ecosystem. This year’s S2S is led and organized by Kevin Bitterman, Ph.D., Partner at Atlas Venture; Jessica Alston, Ph.D., Partner at F-Prime Capital; Matt Cohen, Ph.D., Managing Partner at Osage University Partners; Joshua Resnick, M.D., Managing Director at RA Capital Management; and Jamil Beg, Partner at 5AM Ventures. The keynote address will be delivered by Sangeeta Bhatia, John J. and Dorothy Wilson Professor at MIT’s Institute for Medical Engineering and Science and Electrical Engineering and Computer Science at the Massachusetts Institute of Technology. The ten selected presenters will showcase their discoveries as well as their projected development path toward clinical proof-of-concept. Mentorship for the selected presenters, from experts across multiple disciplines, is facilitated by MassBio. S2S is generously sponsored by Deloitte , Evotec , Goodwin , Jones Lang LaSalle (JLL) , USQ , and Silicon Valley Bank (SVB) . Senior representatives from each sponsor will share their respective expertise with S2S presenters in closed-door workshops prior to the Symposium. “The S2S class of 2023 brings together an impressive group of scientists from some of the world’s top research institutions,” said Dr. Bitterman. “We’re excited to bring back this forum to provide exposure, guidance and mentorship for scientists beginning the often-challenging process of company formation, with the shared goal of increasing the odds of success as they begin the journey of translating their novel ideas into meaningful advances for patients.” “We are thrilled for S2S to return for the third year, especially following the COVID-induced hiatus,” said Dr. Alston. “Our goal is to foster collaboration among Boston’s established biotech ecosystem of investors, mentors and scientists, while also infusing the space with new ideas from entrepreneurs at leading academic institutions, all in service of advancing novel science for the benefit of patients.” Attendees at the event will include senior biopharma executives, life science-focused investors and biotech entrepreneurs. In addition to the presentations, S2S will provide substantial opportunities for networking among the presenters and attendees. “Research universities are at the forefront of pioneering innovative and novel concepts for treating human illness,” said Dr. Cohen. “S2S aims to support academic founders to increase the chance of success for those who may never have been involved in the startup world before.” “S2S aims to bring the best of what Boston has to offer to researchers from around the world,” said Dr. Resnick. “By pairing top scientists with industry mentors who can support them, we aim to both infuse the biotech economy with new ideas while also accelerating the process of therapeutic development. We are delighted to continue to support this event and look forward to seeing what this year’s S2S participants accomplish in the future.” “We are thrilled to be joining S2S this year to work with our peers in the Boston area to connect with a new generation of startups,” said Beg. “The group of scientists slated to present demonstrates a great deal of promise and we’re excited to aid in the advancement of new scientific discoveries.” This year’s ten scientific presenters were selected by an advisory group comprised of experienced biotech investors. S2S received over 125 submissions from 61 institutions across eight countries. The selected presenters are enrolled in a mentorship program led by MassBio, where they will receive one-on-one mentorship from advisory group members and other industry participants, as well as feedback on their scientific translation and drug development plans. S2S’s class of 2023 includes: Sarki Abdulkadir, M.D., Ph.D. , Co-Founder of Vortex Therapeutics, Professor of Urology and Pathology, Northwestern University. Small molecule MYC inhibitors leveraging unique insights into MYC structure and function. Thomas H. Barker, Ph.D. , Co-Founder and CSO, Vasarya Therapeutics; Professor, University of Virginia. Developing targeted treatments for fibrotic disorders. Jonathan Bernardini, Ph.D. , Postdoctoral Researcher, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. BioTACs as a next generation cell surface degrader approach. Jacqueline Burke, Ph.D. , Senior Scientist, DuPage Medical Technology, Inc.; Research Assistant Professor, University of Illinois Chicago. Novel peptide that selectively inhibits platelet and leukocyte activation and high-loading peptide nanoparticles enabling in vivo delivery for the treatment of thrombo-inflammation and ischemia-reperfusion injury. Ken Fujise, M.D. , Professor and the Harold T. Dodge-John L. Locke Chair in Cardiovascular Medicine, University of Washington. Fortilin, a macrophage (MФ) survival molecule, as a new and viable molecular target of atherosclerosis. Paraskevi (Evi) Giannakakou, Ph.D. , Professor of Pharmacology in Medicine and Associate Director of Education at the Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine. First-in-class small molecule inhibitor of androgen receptor splice variant 7, for the treatment of drug-resistant prostate cancer. Peng Ji, M.D., Ph.D. , Professor of Pathology, Northwestern University. Novel small molecule compounds targeting Pleckstrin-2, a newly discovered protein critical for the pathogenesis of myeloproliferative neoplasms. Kirill Martemyanov, Ph.D. , Co-founder, EvoDenovo; Professor and Chair, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology. New strategies for improving safety of opioid drugs and combating opioid use disorder based on innovative discovery of novel drug targets. James H. Morrissey, Ph.D. , Professor, University of Michigan Medical School . Novel platform for the reversal of all types of heparin in current clinical use. James Shayman, M.D. , Professor of Internal Medicine and Pharmacology, University of Michigan Medical School. Next generation inhibitors of glucosylceramide synthase for the treatment of neuronopathic and non-neuronopathic glycosphingolipid storage disorders. For a list of S2S’s 2023 advisors, please visit www.science2startup.com . About Atlas Venture Atlas Venture is a leading biotech venture capital firm. With the goal of doing well by doing good, we have been building breakthrough biotech startups for over 25 years. We work side by side with exceptional scientists and entrepreneurs to translate high impact science into medicines for patients. Our seed-led venture creation strategy rigorously selects and focuses investment on the most compelling opportunities to build scalable businesses and realize value. For more information, please visit www.atlasventure.com . About F-Prime Capital F-Prime Capital is a global venture capital firm investing in healthcare and technology. For the past 50 years, our venture capital group has had the privilege of backing great entrepreneurs building ground-breaking companies. With over $3 billion dollars under management and a global portfolio of more than 200 companies, we champion those dedicated to creating positive change in the world. In healthcare, we focus on therapeutics, medtech and health IT & services in a stage-agnostic fashion. Our healthcare fund has created or co-created 29 companies including Denali, Beam, Innovent, Orchard and Sana and has helped build many others including Blueprint Medicines, Iora Health, PatientPing, Devoted and Ultragenyx. F-Prime portfolio companies have seen more than 32 products and drugs approved by regulatory agencies worldwide. Our team of investors, engineers, doctors and scientists is committed to bringing the insight, domain expertise and relationships required to help our companies make a transformational impact. For more information, please visit www.fprimecapital.com . About Osage University Partners Osage University Partners (OUP) is a venture capital firm focused on investing in startups that are commercializing pioneering university technologies. OUP partners with top research universities to invest in their most innovative startups, and OUP shares its investment profit with its partner institutions. The firm invests in software, hardware, climate tech, and life science companies at all stages of company development. Since 2009, OUP has partnered with over 100 universities, including 27 of the top 30 U.S. institutions by research expenditures, and has invested in over 130 of their spinouts. For more information, visit oup.vc . About RA Capital Management RA Capital Management is a multi-stage investment manager dedicated to evidence-based investing in public and private healthcare and life science companies that are developing drugs, medical devices, and diagnostics. The flexibility of its strategy allows RA Capital to provide seed funding to startups and to lead private, IPO, and follow-on financings for its portfolio companies, both facilitating the crossover process and allowing management teams to drive value creation with fewer capital concerns from inception through commercialization. For more information, please visit www.racap.com . About 5AM Ventures Founded in 2002, 5AM Ventures is a leading venture capital firm focused on building next-generation life science companies. Based in San Francisco and Boston, 5AM takes a hands-on approach to investing and company building, often going beyond traditional board roles to leverage our diverse team of scientists, clinicians, drug developers and executives throughout a company’s life. With over $2.2 billion raised since inception, 5AM has invested globally in over 100 public and private companies. For more information, please visit www.5amventures.com . About MassBio MassBio’s mission is to advance Massachusetts’ leadership in the life sciences to grow the industry, add value to the healthcare system, and improve patient lives. MassBio represents the premier global life sciences and healthcare hub, with 1,600+ members dedicated to preventing, treating, and curing diseases through transformative science and technology that brings value and hope to patients. Founded in 1985, MassBio works to advance policy and promote education, while providing member programs, events, industry information, and services. For more information, visit www.massbio.org .