Agenus announced the presentation of new clinical data for AGEN1181 (Fc-enhanced anti-CTLA-4) as monotherapy and in combination with balstilimab (anti-PD-1) at the Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting. As of the data cut-off date of September 17, 2021, one hundred and sixteen patients received AGEN1181 in a dose escalation study to determine the optimal monotherapy dose and combination dose with balstilimab. Of note, this population was heavily pre-treated, with over half of these patients receiving at least 3 prior lines of therapy and nearly a third of patients receiving prior anti-PD-1 therapy. There were four cases of confirmed objective responses to AGEN1181 monotherapy. These include a complete response (CR) in MSS endometrial cancer, and partial responses (PR) in pancreatic cancer, as well as PD-1 refractory cervical cancer. These are the first reported responses to CTLA-4 monotherapy in these disease settings. The fourth response was in a patient with PD-1 refractory melanoma. Of note, three of the monotherapy responders expressed the low affinity Fc?RIIIA receptor, which is associated with lack of response to first-generation CTLA-4 inhibitors. Significant benefit was also observed with the combination of AGEN1181 and balstilimab across multiple ?cold? cancers studied, with >60% of evaluable patients receiving at least 1 mg/kg AGEN1181 experiencing disease control. Among 20 evaluable patients with microsatellite stable colorectal cancer (MSS-CRC), where PD-1 inhibitors have historically shown limited to no activity2-5, there were three confirmed PRs and one unconfirmed PR. In addition, ten cases of stable disease (SD) were observed, with one patient?s tumor burden reduced by 27%. The disease control rate (DCR) among these MSS CRC patients was 70%. Among 9 evaluable ovarian cancer patients receiving at least 1 mg/kg of AGEN1181 in combination with balstilimab, there were three confirmed PRs and two cases of SD (one of the patients with SD had a 28% reduction of tumor burden). Compelling clinical activity was also seen in MSS-endometrial cancer as both patients treated with combination therapy demonstrated PRs; all three patients with MSS endometrial cancer treated with AGEN1181 (one with monotherapy, two in combination with balstilimab) had objective responses. Additional responders to combination therapy include 1 confirmed PR in a NSCLC patient who failed prior PD-1 therapy, 2 confirmed PRs in visceral angiosarcoma, and 1 unconfirmed PR in leiomyosarcoma.