IMSA101 / ImmuneSensor Therap, Walvax - LARVOL DELTA

Phase 1 first-in-human dose-escalation study of IMSA101, a novel cyclic di-nucleotide STING agonist, for patients with advanced solid tumor malignancies. (PubMed, J Immunother Cancer) - P1/2 | "IMSA101 doses of 1,200 µg (monotherapy arm) and 2,400 µg (combination therapy arm) were well tolerated but demonstrated minimal signals of antitumor activity in patients with advanced solid tumors."

Journal • P1 data • Fatigue • Oncology • Pain • Solid Tumor • PD-L1

SPARK: Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: University of Texas Southwestern Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Study of PULSAR-ICI +/- IMSA101 in Patients with Oligoprogressive Solid Tumor Malignancies (clinicaltrials.gov) - P2 | N=16 | Terminated | Sponsor: ImmuneSensor Therapeutics Inc. | N=51 ➔ 16 | Trial completion date: Feb 2026 ➔ Nov 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2025 ➔ Nov 2024; Change in ImmuneSensor corporate strategy

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor • PD-L1

A Rollover Study for Subjects Who Completed Participation in IMSA101-101 Trial (clinicaltrials.gov) - P1 | N=2 | Active, not recruiting | Sponsor: ImmuneSensor Therapeutics Inc. | Phase classification: P1/2 ➔ P1 | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Metastases • Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Study of PULSAR-ICI +/- IMSA101 in Patients With Oligometastatic NSCLC and RCC (clinicaltrials.gov) - P2 | N=6 | Terminated | Sponsor: ImmuneSensor Therapeutics Inc. | N=46 ➔ 6 | Trial completion date: Feb 2026 ➔ Sep 2024 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2025 ➔ Sep 2024; Slow enrollment.

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Study of PULSAR-ICI +/- IMSA101 in Patients With Oligoprogressive Solid Tumor Malignancies (clinicaltrials.gov) - P2 | N=51 | Active, not recruiting | Sponsor: ImmuneSensor Therapeutics Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • PD-L1

SPARK: Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: University of Texas Southwestern Medical Center

Checkpoint inhibition • Combination therapy • Metastases • New P2 trial • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Two phase 2A clinical trials to evaluate the safety and efficacy of IMSA101 in combination with radiotherapy and checkpoint inhibitors in oligometastatic and oligoprogressive solid tumor malignancies. (ASCO 2024) - P2 | "In both studies, the experimental treatment regimen will consist of 3 doses of PULSAR spaced 1 month apart, either Nivolumab or Pembrolizumab IO therapy per FDA product label and 5 intra-tumoral injections of IMSA101 over a 60-day period. OPD Study: 45 OPD solid tumor patients, randomized 1:2 to control arm vs. experimental arm (control: PULSAR + PD1 Ab, experimental arm: PULSAr + PD-1 Ab + IMSA 101). Primary endpoint: Progression-free rate at 12 months."

Checkpoint inhibition • Clinical • Combination therapy • Metastases • P2a data • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • STING

The STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion. (PubMed, Nat Commun) - "Consistent with this, the use of IL-18 receptor negative CART impair anti-tumor responses in mice receiving combination treatment. In summary, we find that IMSA101 enhances CART function which is facilitated through STING agonist-induced IL-18 secretion."

CAR T-Cell Therapy • Journal • Oncology • Solid Tumor • IL18 • STING

STING agonist IMSA-101 improves CAR T therapy trafficking into tumor (Bioworld) - "Immunesensor Therapeutics Inc. has presented preclinical data on the stimulator of interferon genes (STING) agonist IMSA-101 which is designed to modify the tumor microenvironment in solid tumors and thus improve the trafficking and infiltration of CAR T-cell therapy into the tumor."

Preclinical • Oncology • Solid Tumor

Combining CAR T cells with Newly Developed STING Agonist (EBMT-EHA 2024) - "In summary, we found that i.t. administration of IMSA101 improved CART trafficking into the tumor, induced intratumoral CART activation, and enhanced CART efficacy, which was facilitated through STING agonist-mediated IL-18 induction."

CAR T-Cell Therapy • Oncology • Solid Tumor • IL18 • STING

Phase 1 clinical trial evaluating the safety, biologic and anti-tumor activity of the novel STING agonist IMSA101 administered both as monotherapy and in combination with PD-(L)1 checkpoint inhibitors (SITC 2023) - "Notable efficacy signals with both monotherapy and in combination with ICI were observed. Phase 2 randomized trials evaluating the combination of IMSA101, ICI and pulsed radiotherapy (PULSAR) in the settings of oligometastatic and oligo-progressive disease are now underway."

Checkpoint inhibition • Clinical • Combination therapy • Monotherapy • P1 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CGAS • STING

STING agonist-induced IL-18 secretion enhances CAR T cell function (SITC 2023) - "Conclusions In summary, we found that i. t. administration of IMSA101 promoted CART trafficking into the tumor, induced intratumoral CART activation, and enhanced CART efficacy, which was facilitated through STING agonist-mediated IL-18 induction. These promising observations laid the foundation for advancing the combinatorial approach into a clinic setting which is currently being planned."

CAR T-Cell Therapy • Gastrointestinal Cancer • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • IL18 • STING

A Rollover Study for Subjects Who Completed Participation in IMSA101-101 Trial (clinicaltrials.gov) - P1/2 | N=2 | Active, not recruiting | Sponsor: ImmuneSensor Therapeutics Inc. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Oncology • Solid Tumor

Safety and Efficacy Study of IMSA101 in Refractory Malignancies (clinicaltrials.gov) - P1/2 | N=40 | Completed | Sponsor: ImmuneSensor Therapeutics Inc. | Recruiting ➔ Completed | N=115 ➔ 40 | Trial completion date: Dec 2023 ➔ Sep 2023

Enrollment change • Metastases • Trial completion • Trial completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

A Rollover Study for Subjects Who Completed Participation in IMSA101-101 Trial (clinicaltrials.gov) - P1/2 | N=2 | Not yet recruiting | Sponsor: ImmuneSensor Therapeutics Inc.

New P1/2 trial • Oncology • Solid Tumor

Study of PULSAR-ICI +/- IMSA101 in Patients With Oligoprogressive Solid Tumor Malignancies (clinicaltrials.gov) - P2 | N=51 | Recruiting | Sponsor: ImmuneSensor Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor • PD-L1

Study of PULSAR-ICI +/- IMSA101 in Patients With Oligometastatic NSCLC and RCC (clinicaltrials.gov) - P2 | N=46 | Recruiting | Sponsor: ImmuneSensor Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Immune Modulation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Study of PULSAR-ICI +/- IMSA101 in Patients With Oligoprogressive Solid Tumor Malignancies (clinicaltrials.gov) - P2 | N=51 | Not yet recruiting | Sponsor: ImmuneSensor Therapeutics Inc.

New P2 trial • Immune Modulation • Oncology • Solid Tumor • PD-L1

Study of PULSAR-ICI +/- IMSA101 in Patients With Oligometastatic NSCLC and RCC (clinicaltrials.gov) - P2 | N=46 | Not yet recruiting | Sponsor: ImmuneSensor Therapeutics Inc.

New P2 trial • Immune Modulation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Combining CAR T Cell Therapy with Novel STING Agonist for Successful Treatment of Solid Tumors (ASGCT 2023) - "In summary, intratumoral administration of IMSA101 improved CART trafficking into the tumor, induced intratumoral CART activation, and significantly enhanced overall anti-tumor efficacy and overall survival in two syngeneic flank tumor models and in an immunodeficient model with human CART, suggesting direct and indirect mechanisms of enhanced antitumor immunity. These promising results paved the way for development of the combination approach into the clinic."

CAR T-Cell Therapy • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • STING

Safety and Efficacy Study of IMSA101 in Refractory Malignancies (clinicaltrials.gov) - P1/2 | N=115 | Recruiting | Sponsor: ImmuneSensor Therapeutics Inc. | Trial completion date: Feb 2023 ➔ Dec 2023 | Trial primary completion date: Feb 2023 ➔ Oct 2023

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hormone Receptor Breast Cancer • Immune Modulation • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

ImmuneSensor Awarded $16 Million Grant from the Cancer Prevention and Research Institute of Texas (CPRIT) (GlobeNewswire) - "ImmuneSensor Therapeutics Inc...announced the Company has been awarded a $16.1 million Product Development Research Grant from the Cancer Prevention and Research Institute of Texas ('CPRIT') to advance Phase 2 studies evaluating IMSA101, a STING agonist, in combination with immune checkpoint inhibitors ('ICI') and radiotherapy for the treatment of metastatic solid tumor malignancies....'We look forward to initiating our Phase 2 trials to further investigate the role of the cGAS-STING pathway in boosting anticancer immunity in cancer patients'."

Financing • Trial status • Oncology • Solid Tumor

Safety and Efficacy Study of IMSA101 in Refractory Malignancies (clinicaltrials.gov) - P1/2; N=115; Recruiting; Sponsor: ImmuneSensor Therapeutics Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Genor Bio’s STING agonist GB492 picks up trial nod in China (GBI Health) - "China’s Genor Biopharma Co., Ltd (6998.HK) announced that it has received clinical trial approval from the National Medical Products Administration (NMPA) for its stimulator of interferon genes (STING) agonist GB492 in advanced refractory malignant tumors combined with a programmed-death-1/ligand 1 inhibitor. Multiple studies have shown that the combination of STING agonists and other immune checkpoint inhibitors can activate the cGAS-STING signaling pathway and enhance the efficacy of the tumor immune cycle. Genor Bio struck a licensing deal with ImmuneSensor Therapeutic in June 2020, taking exclusive rights to GB492."

Non-US regulatory • Oncology