Do not make unauthorized copies. Figure 5 . Long term survival by cancer type of patients entered into Vigil Phase I trial. Moreover, correlation of survival benefit with recent follow up involving the first 30 Phase I patients to receive Vigil to γIFN ELISPOT response which measures Vigil turned on circulating immune cells (T effector cells) against autologous tumor suggests efficacy tied to predicted mechanism of Vigil (Figure 6). Ph III Ewing’s Sarcoma Vigil ± Irinotecan +Temozolomide IND 014205 CL-PTL-130 Version: 03 Page 26 of 74 Confidential and proprietary information of Gradalis, Inc. Effective: 05-DEC-2018 It is the user’s responsibility to verify adequate training before executing a document. Do not make unauthorized copies. Group N Median (mo.) p-value Group N Median (mo.) p-value ELISPOT ( -) 15 17.2 0.00015 ELISPOT ( -) 15 6.4 0.00010 ELISPOT (+) 52 38.5 ELISPOT (+) 52 28.7 Figure 6 . Correlated survival and immune response and updated analysis of Vigil Phase 1 patients. 78% ELISPOT conversion rate. 55% ELISPOT (+) patients are still alive vs. 13% ELISPOT (-) are deceased. (Analysis performed on 02/27/17) These results have recently been updated ( Figure 6). Sixty -seven (67) of these Phase I patients have now undergone IFNγ ELISPOT testing. Fifty -two demonstrated change from negative at baseline (prior to Vigil treatment) to positive IFNγ ELIPSOT reactivity after Vigil (78% conversion rate). However, fifteen failed to show upregulation of circulating active effector T cells against autologous tumor induction by Vigil. Survival correlation continues to be demonstrated in this 4-year updated analysis. 2.1 Vigil Phase II Trial: Ovarian Cancer Based on positive Phase I results, a 2:1 (Vigil:Control) randomized Phase IIa open-label trial of Vigil (tumor harvested at the time of surgical debulking), in patients with Stage III/IV ovarian cancer, who achieved clinical complete response (cCR) following primary surgical debulking and standard chemotherapy (5-6 cycles, front-line maintenance setting), was initiated (CL-PTL-105). A 1.0 x 10 7 dose of transfected autologous tumor cells/intradermal injection was administered once a month for up to 12 doses to the treatment group. Standard of care was provided for the control patients. Cross -over was allowed at time of relapse for patients randomized to standard of care therapy. Results have been published by Oh et al (Oh, Barve et al. 2016) . Ph III Ewing’s Sarcoma Vigil ± Irinotecan +Temozolomide IND 014205 CL-PTL-130 Version: 03 Page 27 of 74 Confidential and proprietary information of Gradalis, Inc. Effective: 05-DEC-2018 It is the user’s responsibility to verify adequate training before executing a document. Do not make unauthorized copies. Twenty -one patients were randomized to Vigil, 11 to control standard of care. Discussion of these results lead to a larger (currently ongoing) Phase II/III trial design. Once the Phase II/III trial was initiated study CL-PTL-105 was closed to further accrual and patients not yet randomized in consolidation chemotherapy section entered the Vigil arm. Thirty -one patients received Vigil as part of the Phase IIa trial (11 were randomized to control standard of care). Demographics revealed no significant differences between the 2 groups. No ≥ Grade 3 adverse events were observed related to Vigil. Efficacy with respect to time to relapse induced immune response is shown in Figure 7. Group N Median (mo.) p-value Control 11 12.4 0.025 Vigil 31 19.8 Figure 7 . Correlated survival of Vigil compared to control in Ovarian Cancer (CL-PTL 105) with immune responses. OV -1049 and OV-1074 were censored at time of cross-over. OV-1049 crossed-over and started Vigil 08/27/14 (5 cycles) and relapsed 4 months after treatment start (12/17/14). Ph III Ewing’s Sarcoma Vigil ± Irinotecan +Temozolomide IND 014205 CL-PTL-130 Version: 03 Page 28 of 74 Confidential and proprietary information of Gradalis, Inc. Effective: 05-DEC-2018 It is the user’s responsibility to verify adequate training before executing a document. Do not make unauthorized copies. ELISPOT Conversion At Baseline Post Vigil Treatment Vigil 1/31 (0.3%) 31/31 (100% Conversion) Median spots 134 (12-448) Control 0/8 7/8 (cross -over) Median spots 58 (43-105) Figure 8 . ELISPOT response of Vigil in Ovarian Cancer (CL-PTL-105). Thirty -one (31) patients are ELISPOT (+) post Vigil treatment. These positive results were associated with robust ELISPOT response ( Figure 7). Less than 3% of ovarian patients had circulating T cells with capacity to release IFNγ and induce autologous tumor necrosis at baseline (prior to Vigil), however following Vigil treatment 31/31 patients demonstrated brisk antitumor immune activity. No control patients demonstrated circulating T cell response against autologous tumor during or after standard of care, or at time of relapse. Ninety percent (90%, 7 of 8) demonstrated autologous tumoricidal activity of circulating T cells by IFNγ ELISPOT response, after cross -over. Interestingly, ELISPOT reactivity response was only 43% of what was observed with Vigil prior to relapse (134 spots vs. 58 spots) (Figure 8). Ph III Ewing’s Sarcoma Vigil ± Irinotecan +Temozolomide IND 014205 CL-PTL-130 Version: 03 Page 29 of 74 Confidential and proprietary information of Gradalis, Inc. Effective: 05-DEC-2018 It is the user’s responsibility to verify adequate training before executing a document. Do not make unauthorized copies. 2.2 Vigil Phase I Trial: Ewing’s sarcoma Subset Initial results of 12 Ewing’s sarcoma Vigil treated patients entered into CL-PTL-101 were published two years ago (Ghisoli, Barve et al. 2015). A total of 30 Ewing’s sarcoma patients have now been enrolled into CL-PTL-101 with intent to treat and procurement for EWS Vigil manufacture. All patients had late stage Ewing’s sarcoma (majority ≥ third line chemotherapy). Sixteen of these patients received Vigil. Fourteen concurrent patients who did not receive Vigil after undergoing similar surgery and Vigil manufacture served as control. Nine of the latter were unable to have vaccine released (6 contaminants, 3 insufficient viable tumor cells) and five chose other treatment management. All products constructed fulfilled release criteria of GMCSF production and TGFβ1, β2 knockdown. See demographics in Table 2.