Forty Seven, Inc. announced updated data from its ongoing Phase 1b/2 clinical trial evaluating 5F9 in combination with rituximab for the treatment of relapsed/refractory non-Hodgkin’s lymphoma (r/r NHL), including diffuse large B-cell lymphoma (DLBCL) and indolent lymphoma. The data will be presented in an oral session at the 24thCongress of the European Hematology Association (EHA) in Amsterdam, Netherlands. Also at EHA, Forty Seven will present data from its ongoing Phase 1b clinical trial evaluating 5F9 as a monotherapy and in combination with azacitidine for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which were previously presented at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting. Forty Seven’s Phase 1b/2 trial, which is being funded in part by the Leukemia and Lymphoma Society (LLS) through the Therapy Acceleration Program® (TAP), is designed to evaluate 5F9 in combination with rituximab in patients with r/r B-cell NHL, who have failed standard-of-care therapies. All patients received a 1 mg/kg priming dose of 5F9 to mitigate on-target anemia. Patients in the Phase 1b portion of the trial were treated with 5F9 maintenance doses of 10 to 45 mg/kg, and patients in the Phase 2 portion of the trial were treated with 5F9 doses of either 30 or 45 mg/kg. All patients were also administered full doses of rituximab. As of the data cutoff of May 2019, 115 patients had been treated in the Phase 1b/2 trial, including 70 patients with DLBCL, 41 patients with follicular lymphoma (FL) and four patients with marginal zone lymphoma (MZL). The median number of prior therapies across all patients was three (range one to 10), and 85% of all patients were refractory to a prior rituximab-containing regimen, with 59% of DLBCL patients having primary refractory disease. Additionally, 42 of the 47 DLBCL patients enrolled in the Phase 2 portion of the trial were ineligible for CAR-T therapy (89%). As of the data cutoff, 5F9 was well-tolerated in combination with rituximab. Adverse events (AEs) were consistent with prior clinical experience. Most AEs were Grade 1 or Grade 2, and the most commonly-reported AEs were expected CD47-mechanism-based effects on red blood cells, which led to a temporary and reversible anemia, and infusion-site reactions. No autoimmune-related AEs were observed, nor were any significant late safety signals observed in patients treated with 5F9 for up to 24 months. No maximum tolerated dose was reached with up to 45 mg/kg of 5F9 dosing. Eight out of 115 patients discontinued treatment due to an AE (7%). As of the data cutoff, 97 patients were evaluable for response assessment, including 21 relapsed/refractory DLBCL patients who were treated in the Phase 1b portion of the study, 38 DLBCL patients who were treated in the Phase 2 portion of the study and 38 indolent lymphoma patients (35 patients with FL and three patients with MZL). Among patients treated in the Phase 1b portion of the trial, the median duration of response has not been reached, with a median follow-up of over 13.8 months. This includes one patient who has remained in a durable complete response (CR) for more than 24 months. Among patients treated in the Phase 1b portion of the trial, the median duration of response has not been reached with a median follow-up of over 21 months. This includes the patient who has remained in a durable CR for more than 28 months. Additionally, 5F9 tumor penetrance was evaluated at 30 and 45 mg/kg as a key pharmacodynamic endpoint. Data show that the 30 mg/kg maintenance dose of 5F9 saturated the tumor microenvironment similarly to 45 mg/kg, with similar efficacy. As a result, a 30 mg/kg maintenance dose of 5F9 was selected as the recommended dose for use in future clinical studies. Based on feedback from a Type C meeting with the FDA in May 2019, Forty Seven believes that data from a single arm pivotal study evaluating ORR and durability may be sufficient to support the registration of 5F9 in combination with rituximab in patients with r/r DLBCL who have failed at least two prior lines of therapy, including those who have been deemed CAR-T ineligible. The Company is currently finalizing the operational components of the proposed registrational study, including details on trial design and chemistry, manufacturing and controls (CMC), and will provide a detailed update in the second half of 2019. In parallel, the Company will continue ongoing efforts to evaluate 5F9 as part of additional combination regimens for patients with DLBCL, including in patients in earlier lines of treatment. This includes the planned triplet regimen of 5F9, rituximab and atezolizumab, which Forty Seven is evaluating in collaboration with Genentech, and the planned triplet regimen of 5F9, rituximab and acalabrutinib, which Forty Seven is evaluating in collaboration with Acerta Pharma, in addition to potential studies of 5F9 in combination with other targeted antibodies. Forty Seven will also evaluate opportunities to advance 5F9 in combination with rituximab for patients with indolent lymphoma. As Forty Seven previously presented at the 2019 ASCO Annual Meeting in June 2019, data from the ongoing Phase 1b clinical trial of 5F9 in MDS and AML showed an ORR of 100% and a CR rate of 55% in higher-risk MDS patients treated with 5F9 in combination with azacitidine and an ORR of 64% and a CR/complete response with incomplete blood count recovery (CRi) rate of 50% in untreated AML patients treated with 5F9 in combination with azacitidine. In addition, the combination was well-tolerated, with no evidence of increased toxicities compared to azacitidine alone. Based on the favorable safety profile and encouraging clinical activity observed in this Phase 1b clinical trial, expansion cohorts have been initiated in patients with both higher-risk MDS and untreated AML with 5F9 in combination with azacitidine. In addition, based on feedback from a Type B meeting with the FDA in May 2019, Forty Seven believes that data from a single pivotal study may be sufficient to support the registration of 5F9 in combination with azacitidine in patients with untreated, higher-risk MDS. The Company is finalizing the details of the proposed registrational study, and will provide a detailed update in the second half of 2019.