Presentation Date: 6/9/2024 Presentation Start Time: 1:33:00 PM In sickle cell disease (SCD), a beta-globin gene single point mutation results in hemoglobin S (HbS) production, which can polymerize upon deoxygenation. Polymerization distorts the red blood cell membrane, generating sickled red blood cells and contributing to microvascular occlusions, which may present as acute, painful vaso-occlusive episodes (VOEs). Among patients with SCD, 70% of emergency department visits and 90% of hospitalizations are VOE-related.1,2 Despite the availability of treatments for VOE prevention, considerable morbidity and mortality remain. Due to a lack of targeted therapies, acute VOE treatment is limited to supportive care. Nonclinical data suggest a multimodal role for complement dysregulation in the pathophysiology of SCD, including in vaso-occlusion, hemolysis, inflammation, endothelial activation, thrombogenicity, and end-organ damage.3 Crovalimab is a novel, engineered, anti-complement C5 monoclonal antibody that allows for small-volume subcutaneous injection after an initial intravenous loading dose.4 Here, we describe the design of two randomized, double-blind, placebo-controlled trials evaluating crovalimab in patients with SCD: CROSSWALK-a (Phase 1b; NCT04912869) and CROSSWALK-c (Phase 2a; NCT05075824). CROSSWALK-a evaluates the safety of crovalimab in managing acute uncomplicated VOEs. CROSSWALK-c evaluates the efficacy and safety of crovalimab as adjunct therapy in preventing VOEs. Patients between 12 and 55 years of age, weighing ≥40 kg, having a confirmed diagnosis of sickle cell anemia (homozygous HbSS or heterozygous HbS/β0 thalassemia), and N. meningitidis, H. influenzae type B and S. pneumoniae vaccinations are eligible (Fig. 1 and 2). Concurrent SCD-directed therapies are allowed. CROSSWALK-a and CROSSWALK-c are currently actively enrolling patients with SCD in 6 and 7 countries, respectively. References 1. Ballas et al, Am J Hematol 2005; 79:17–25. 2. Lanzkron et al, Am J Hematol 2010; 85:797–799. 3. Roumenina et al, Am J Hematol 2020; 95:456–464. 4. Röth et al, Blood 2020; 135:912–920. © American Society of Hematology (2023). Reused with permission.

Allison W Hsia; Marco Aurélio Salvino; Bulent Antmen; Fredrick Chite Asirwa; Satheesh Chonat; Lucia de Franceschi; Perla Eleftheriou; Adlette Inati; Johnny Mahlangu; Erfan Nur; Salvador Payán-Pernía; Asad Charania; Diana Gradinaru; Yves Luder; Thomas Perretti; Sasha Sreckovic; Pablo Bartolucci. Randomized Phase 1b CROSSWALK-a and Phase 2a CROSSWALK-c Trials Crovalimab for SCD. Journal of Sickle Cell Disease 2024, 1 .

Allison W Hsia, Marco Aurélio Salvino, Bulent Antmen, Fredrick Chite Asirwa, Satheesh Chonat, Lucia de Franceschi, Perla Eleftheriou, Adlette Inati, Johnny Mahlangu, Erfan Nur, Salvador Payán-Pernía, Asad Charania, Diana Gradinaru, Yves Luder, Thomas Perretti, Sasha Sreckovic, Pablo Bartolucci. Randomized Phase 1b CROSSWALK-a and Phase 2a CROSSWALK-c Trials Crovalimab for SCD. Journal of Sickle Cell Disease. 2024; 1 (Supplement):.

Allison W Hsia; Marco Aurélio Salvino; Bulent Antmen; Fredrick Chite Asirwa; Satheesh Chonat; Lucia de Franceschi; Perla Eleftheriou; Adlette Inati; Johnny Mahlangu; Erfan Nur; Salvador Payán-Pernía; Asad Charania; Diana Gradinaru; Yves Luder; Thomas Perretti; Sasha Sreckovic; Pablo Bartolucci. 2024. "Randomized Phase 1b CROSSWALK-a and Phase 2a CROSSWALK-c Trials Crovalimab for SCD." Journal of Sickle Cell Disease 1, no. Supplement: .

Clarisse Martins Machado; Marcia Garnica Maiolino; Jessica Fernandes Ramos; Fabianne Carlesse; Ana Verena de Almeida Mendes. Dengue transmission by graft or blood transfusion in HCT recipients. JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY 2024, 5, 230 -230.

Clarisse Martins Machado, Marcia Garnica Maiolino, Jessica Fernandes Ramos, Fabianne Carlesse, Ana Verena de Almeida Mendes. Dengue transmission by graft or blood transfusion in HCT recipients. JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY. 2024; 5 (1):230-230.

Clarisse Martins Machado; Marcia Garnica Maiolino; Jessica Fernandes Ramos; Fabianne Carlesse; Ana Verena de Almeida Mendes. 2024. "Dengue transmission by graft or blood transfusion in HCT recipients." JOURNAL OF BONE MARROW TRANSPLANTATION AND CELLULAR THERAPY 5, no. 1: 230-230.

Lorena Lobo de Figueiredo-Pontes; Luiz Fernando Bazzo Catto; Maria de Lourdes Lopes Ferrari Chauffaille; Katia Borgia Barbosa Pagnano; Maria Isabel Ayrosa Madeira; Elenaide Coutinho Nunes; Nelson Hamerschlak; Marcela Cavalcante de Andrade Silva; Thiago Xavier Carneiro; Teresa Cristina Bortolheiro; Tiago Thalles de Freitas; Rosane Isabel Bittencourt; Evandro Maranhão Fagundes; Eduardo Magalhães Rego. Diagnosis and management of acute promyelocytic leukemia: Brazilian consensus guidelines 2024 on behalf of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy. Hematology, Transfusion and Cell Therapy 2024 .

Lorena Lobo de Figueiredo-Pontes, Luiz Fernando Bazzo Catto, Maria de Lourdes Lopes Ferrari Chauffaille, Katia Borgia Barbosa Pagnano, Maria Isabel Ayrosa Madeira, Elenaide Coutinho Nunes, Nelson Hamerschlak, Marcela Cavalcante de Andrade Silva, Thiago Xavier Carneiro, Teresa Cristina Bortolheiro, Tiago Thalles de Freitas, Rosane Isabel Bittencourt, Evandro Maranhão Fagundes, Eduardo Magalhães Rego. Diagnosis and management of acute promyelocytic leukemia: Brazilian consensus guidelines 2024 on behalf of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy. Hematology, Transfusion and Cell Therapy. 2024; ():.

Lorena Lobo de Figueiredo-Pontes; Luiz Fernando Bazzo Catto; Maria de Lourdes Lopes Ferrari Chauffaille; Katia Borgia Barbosa Pagnano; Maria Isabel Ayrosa Madeira; Elenaide Coutinho Nunes; Nelson Hamerschlak; Marcela Cavalcante de Andrade Silva; Thiago Xavier Carneiro; Teresa Cristina Bortolheiro; Tiago Thalles de Freitas; Rosane Isabel Bittencourt; Evandro Maranhão Fagundes; Eduardo Magalhães Rego. 2024. "Diagnosis and management of acute promyelocytic leukemia: Brazilian consensus guidelines 2024 on behalf of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy." Hematology, Transfusion and Cell Therapy , no. : .