• 4 doses (20mg/day, 40mg/day, 80mg/day, and 120mg/day)
• 14 oral daily doses of veledimex
• 1 Expansion cohort at a single dose level at or below MTD

From the protocol: Veledimex PK parameters to be determined will include, but are not limited to, the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), half-life (t1/2), area-under-the-concentration versus time curve (AUC), volume of distribution (Vd), and clearance (CL).

From the SAP: The PK blood sample collection was performed either pre-dose or 3-5 hours post-dose, therefore only Cmax and Ctrough will be summarized and plotted. Veledimex concentration ratio between brain tumor and blood will be assessed on Day 0 samples. There will be no parameters including time to maximum plasma concentration (Tmax), half-life (t1/2), area under the curve (AUC), volume of distribution (Vd), and clearance (CL). Cmax will be determined from the maximum plasma concentration from Day 0 (post veledimex and resection/craniotomy), 3-5 hours after the veledimex dose on Day 1, and 3-5 hours after the veledimex dose on Day 14.

Peak serum IL-12 and I downstream IFN-gamma expressions between Day 3 to Day 28 are reported by dose cohort.

For the ORR calculation, responders are defined as those experiencing a confirmed complete response or confirmed partial response. Non-responders are those either with stable or progressive disease. Those subjects that cannot be assessed will be treated as non-responders for the purposes of deriving the percentage of responders and confidence intervals. The ORR is reported overall by treatment arm based on the investigator response at timepoints 56 days, Week 16, Week 24, and Week 48.

PFS (progression free survival) is the time in months from the first treatment (either veledimex or Ad-RTS-hIL-12) to the first assessment on which the overall response is reported as disease progression. Subjects withdrawing from the study will be censored at their last non progressive disease response assessment. If a subject does not have a non-progressive disease response assessment, the subject will be censored on the date of the first treatment as described above.

OS is defined as the duration of time from the first dose of study drug (Day 0) to the date of death from any cause in days or months. Subjects are censored based on the last date known to be alive. For example:

• Subjects who discontinue the study without documentation of additional follow-up will be censored at the date of discontinuation.
• Subjects who are lost to follow-up will be censored at last follow-up contact date.
• Subjects still alive up to 2 years from the first dose of study drug are classified as censored and as having completed all follow-up scheduling.

From the protocol: Veledimex PK parameters to be determined will include, but are not limited to, the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), half-life (t1/2), area-under-the-concentration versus time curve (AUC), volume of distribution (Vd), and clearance (CL).

From the SAP: The PK blood sample collection was performed either pre-dose or 3-5 hours post-dose, therefore only Cmax and Ctrough will be summarized and plotted. Veledimex concentration ratio between brain tumor and blood will be assessed on Day 0 samples. There will be no parameters including time to maximum plasma concentration (Tmax), half-life (t1/2), area under the curve (AUC), volume of distribution (Vd), and clearance (CL). Cmax will be determined from the maximum plasma concentration from Day 0 (post veledimex and resection/craniotomy), 3-5 hours after the veledimex dose on Day 1, and 3-5 hours after the veledimex dose on Day 14.

Group 1: Subjects scheduled for craniotomy and tumor resection: Subjects with a clinical indication for tumor resection will receive veledimex 30 mg/day 3 (± 2) hours before the craniotomy procedure.

Group 1: Subjects scheduled for craniotomy and tumor resection: Subjects with a clinical indication for tumor resection will receive veledimex 40 mg/day 3 (± 2) hours before the craniotomy procedure.

Subjects who will not undergo tumor resection will receive Ad-RTS-hIL-12 by standard stereotactic surgery on Day 0. After the Ad-RTS-hIL-12 injection, veledimex 20 mg/day will be administered orally for 14 days.

Total of all reporting groups

Group 1: Subjects scheduled for craniotomy and tumor resection: Subjects with a clinical indication for tumor resection will receive veledimex 20 mg/day 3 (± 2) hours before the craniotomy procedure.

Group 1: Subjects scheduled for craniotomy and tumor resection: Subjects with a clinical indication for tumor resection will receive veledimex 30 mg/day 3 (± 2) hours before the craniotomy procedure.

Group 1: Subjects scheduled for craniotomy and tumor resection: Subjects with a clinical indication for tumor resection will receive veledimex 40 mg/day 3 (± 2) hours before the craniotomy procedure.

Subjects who will not undergo tumor resection will receive Ad-RTS-hIL-12 by standard stereotactic surgery on Day 0. After the Ad-RTS-hIL-12 injection, veledimex 20 mg/day will be administered orally for 14 days.

The protocol defined the MTD as the dose level below at which less than 33% of subjects, of the same cohort in a group, experienced DLTs, with an independent assessment of Group 1 and Group 2 subjects.

• The number of DLTs and the proportion of subjects with any DLT and each type of DLT were summarized by veledimex dose within each group.

•The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP was used for analysis of DLTs.

From the protocol: Veledimex PK parameters to be determined will include, but are not limited to, the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), half-life (t1/2), area-under-the-concentration versus time curve (AUC), volume of distribution (Vd), and clearance (CL).

From the SAP: The PK blood sample collection was performed either pre-dose or 3-5 hours post-dose, therefore only Cmax and Ctrough will be summarized and plotted. Veledimex concentration ratio between brain tumor and blood will be assessed on Day 0 samples. There will be no parameters including time to maximum plasma concentration (Tmax), half-life (t1/2), area under the curve (AUC), volume of distribution (Vd), and clearance (CL). Cmax will be determined from the maximum plasma concentration from Day 0 (post veledimex and resection/craniotomy), 3-5 hours after the veledimex dose on Day 1, and 3-5 hours after the veledimex dose on Day 14.

The Pharmacokinetic Population (PKP) includes all subjects who received veledimex and have PK samples to be measured.

Peak serum IL-12 and I downstream IFN-gamma expressions between Day 3 to Day 28 are reported by dose cohort.

The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP is denoted as the Per Protocol population in this uncontrolled setting.

For the ORR calculation, responders are defined as those experiencing a confirmed complete response or confirmed partial response. Non-responders are those either with stable or progressive disease. Those subjects that cannot be assessed will be treated as non-responders for the purposes of deriving the percentage of responders and confidence intervals. The ORR is reported overall by treatment arm based on the investigator response at timepoints 56 days, Week 16, Week 24, and Week 48.

The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. The ESP is to be used for analysis of dose limiting toxicities, overall survival and progression free survival and finding the maximum tolerated dose.

PFS (progression free survival) is the time in months from the first treatment (either veledimex or Ad-RTS-hIL-12) to the first assessment on which the overall response is reported as disease progression. Subjects withdrawing from the study will be censored at their last non progressive disease response assessment. If a subject does not have a non-progressive disease response assessment, the subject will be censored on the date of the first treatment as described above.

The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration.

OS is defined as the duration of time from the first dose of study drug (Day 0) to the date of death from any cause in days or months. Subjects are censored based on the last date known to be alive. For example:

• Subjects who discontinue the study without documentation of additional follow-up will be censored at the date of discontinuation.
• Subjects who are lost to follow-up will be censored at last follow-up contact date.
• Subjects still alive up to 2 years from the first dose of study drug are classified as censored and as having completed all follow-up scheduling.

The Evaluable Safety Population (ESP) includes subjects who have received Ad-RTS-hIL-12 and at least one dose of veledimex after Ad-RTS-hIL-12 administration. Overall survival was reported by time point for the following set of subjects of the ESP: ATI001-102 Main Group 1: Craniotomy (treated at 20 mg veledimex: n=15).

From the protocol: Veledimex PK parameters to be determined will include, but are not limited to, the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), half-life (t1/2), area-under-the-concentration versus time curve (AUC), volume of distribution (Vd), and clearance (CL).

From the SAP: The PK blood sample collection was performed either pre-dose or 3-5 hours post-dose, therefore only Cmax and Ctrough will be summarized and plotted. Veledimex concentration ratio between brain tumor and blood will be assessed on Day 0 samples. There will be no parameters including time to maximum plasma concentration (Tmax), half-life (t1/2), area under the curve (AUC), volume of distribution (Vd), and clearance (CL). Cmax will be determined from the maximum plasma concentration from Day 0 (post veledimex and resection/craniotomy), 3-5 hours after the veledimex dose on Day 1, and 3-5 hours after the veledimex dose on Day 14.

The Pharmacokinetic Population (PKP) includes all subjects who received veledimex and have PK samples to be measured.

Group 1: Subjects scheduled for craniotomy and tumor resection: Subjects with a clinical indication for tumor resection will receive veledimex 20 mg/day 3 (± 2) hours before the craniotomy procedure.

Group 1: Subjects scheduled for craniotomy and tumor resection: Subjects with a clinical indication for tumor resection will receive veledimex 30 mg/day 3 (± 2) hours before the craniotomy procedure.

Group 1: Subjects scheduled for craniotomy and tumor resection: Subjects with a clinical indication for tumor resection will receive veledimex 40 mg/day 3 (± 2) hours before the craniotomy procedure.

Subjects who will not undergo tumor resection will receive Ad-RTS-hIL-12 by standard stereotactic surgery on Day 0. After the Ad-RTS-hIL-12 injection, veledimex 20 mg/day will be administered orally for 14 days.