SGT-53 / SynerGene Therap - LARVOL DELTA

SGT53-02-1: Study of Combined SGT-53 Plus Gemcitabine/Nab-Paclitaxel for Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=28 | Active, not recruiting | Sponsor: SynerGene Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Dec 2026 | Trial primary completion date: Dec 2022 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Gene Therapies • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Study of SGT-53 in Children With Refractory or Recurrent Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Suspended | Sponsor: SynerGene Therapeutics, Inc. | Trial completion date: Dec 2023 ➔ Dec 2026 | Trial primary completion date: Dec 2022 ➔ Dec 2025

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Novel P53 Nanomedicine Reduces Immunosuppression and Augments Anti-PD-1 Therapy for Non-Small Cell Lung Cancer in Syngeneic Mouse Models. (PubMed, Cells) - "Our data indicate that SGT-53 can restore effective immune responses against lung cancer cells by reducing immuno-suppressive cells (M2 macrophages and regulatory T cells) and by downregulating immunosuppressive molecules (e.g., galectin-1, a negative regulator of T cell activation and survival) while increasing activity of cytotoxic T cells. These results suggest that combining SGT-53 with anti-PD-1 immunotherapy could increase the fraction of lung cancer patients that responds to anti-PD-1 therapy and support evaluation of this combination particularly in patients with ICI-resistant lung cancers."

Journal • Preclinical • Gene Therapies • Immune Modulation • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LGALS1 • TP53

SGT-53, Carboplatin, and Pembrolizumab for the Treatment of Metastatic Triple Negative Inflammatory Breast Cancer (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Northwestern University | Trial completion date: Sep 2026 ➔ Nov 2022 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Sep 2025 ➔ Nov 2022

IO biomarker • Trial completion date • Trial primary completion date • Trial withdrawal • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

TP53 Gene Therapy as a Potential Treatment for Patients with COVID-19. (PubMed, Viruses) - "We herein summarize the rationale for repurposing SGT-53 as a therapy for infection by SARS-CoV-2, the pathogen responsible for the COVID-19 pandemic. Because p53 regulation was found to play a crucial role in different infection stages of a wide variety of viruses, it is rational to believe that restoring p53 function based on SGT-53 treatment may lead to beneficial therapeutic outcomes for infectious disease at large including heretofore unknown viral pathogens that may emerge in the future."

Journal • Gastrointestinal Cancer • Gene Therapies • Hepatology • Infectious Disease • Novel Coronavirus Disease • Oncology • Pancreatic Cancer • Respiratory Diseases • Solid Tumor • TP53

SGT53-02-1: Study of Combined SGT-53 Plus Gemcitabine/Nab-Paclitaxel for Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: SynerGene Therapeutics, Inc. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Gene Therapies • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Study of SGT-53 in Children With Refractory or Recurrent Solid Tumors (clinicaltrials.gov) - P1 | N=18 | Suspended | Sponsor: SynerGene Therapeutics, Inc. | Trial completion date: Dec 2021 ➔ Dec 2023 | Active, not recruiting ➔ Suspended | Trial primary completion date: Dec 2021 ➔ Dec 2022

Trial completion date • Trial primary completion date • Trial suspension • Oncology • Solid Tumor

SGT-53 in Children With Recurrent or Progressive CNS Malignancies (clinicaltrials.gov) - P1 | N=6 | Not yet recruiting | Sponsor: SynerGene Therapeutics, Inc. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Oncology • CDKN1A • MDM2 • MGMT

SGT-53, Carboplatin, and Pembrolizumab for the Treatment of Metastatic Triple Negative Inflammatory Breast Cancer (clinicaltrials.gov) - P1; N=9; Not yet recruiting; Sponsor: Northwestern University

Clinical • IO biomarker • New P1 trial • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

A Study of SGT-53 in Children With Refractory or Recurrent Solid Tumors (clinicaltrials.gov) - P1; N=18; Active, not recruiting; Sponsor: SynerGene Therapeutics, Inc.; Trial primary completion date: Jun 2021 ➔ Dec 2021

Clinical • Trial primary completion date • Oncology • Solid Tumor

[VIRTUAL] A phase II trial combining tumor-targeting TP53 gene therapy with gemcitabine/nab-paclitaxel as a second-line treatment for metastatic pancreatic cancer. (ASCO 2021) - P2 | "Our data suggest a clinically meaningful benefit of adding SGT-53 to GEM/ABX particularly for second-line PAC patients, most of whom had failed prior FFX treatment."

Clinical • P2 data • Gastrointestinal Cancer • Gene Therapies • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Cancer antigen 19-9 • TP53

Study of Combined SGT-53 Plus Gemcitabine/Nab-Paclitaxel for Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2; N=28; Recruiting; Sponsor: SynerGene Therapeutics, Inc.; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2020 ➔ Dec 2021

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Gene Therapies • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

A Study of SGT-53 in Children With Refractory or Recurrent Solid Tumors (clinicaltrials.gov) - P1; N=18; Active, not recruiting; Sponsor: SynerGene Therapeutics, Inc.; Recruiting ➔ Active, not recruiting; Trial primary completion date: Nov 2020 ➔ Jun 2021

Clinical • Enrollment closed • Trial primary completion date • Oncology • Solid Tumor

SGT-53 in Children With Recurrent or Progressive CNS Malignancies (clinicaltrials.gov) - P1; N=6; Not yet recruiting; Sponsor: SynerGene Therapeutics, Inc.; Trial completion date: Dec 2022 ➔ Dec 2023; Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Oncology

[VIRTUAL] Selective Inhibitors Targeting Lineage Plasticity Driven Antiandrogen Resistance in Prostate Cancer (PCF 2020) - "Second-generation Androgen Receptor (AR) targeted therapies, such as abiraterone, enzalutamide and apalutamide, have significantly improved the survival of men with metastatic Castration-Resistant Prostate Cancer (mCRPC)...Based on our previous findings, we first established a stable CRISPR-sgTP53/RB1-ER cell line that has a significantly elevated enzalutamide resistance, neuroendocrine marker genes and SOX2 expression...Then we will optimize the final 2-3 inhibitors via a medicinal chemistry campaign and examine their efficacy in various prostate cancer models. The successful completion of this project will lead to novel inhibitors that may reverse the lineage plasticity driven antiandrogen resistance, and substantially improve the clinical outcome of patients with mCRPC.Funding Acknowledgments: This work is funded by the Prostate Cancer Foundation 2017 Andy Astrachan and Marc Utay Young Investigator Award (#2017YI1893), NIH R00CA218885-02, DoD W81XWH-18-1-0411, CPRIT..."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • RB1 • SOX2

A Study of SGT-53 in Children With Refractory or Recurrent Solid Tumors (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: SynerGene Therapeutics, Inc.; Trial primary completion date: Nov 2017 ➔ Nov 2018

Trial primary completion date • Biosimilar • Hematological Malignancies • Oncology

Combination with SGT-53 overcomes tumor resistance to a checkpoint inhibitor. (PubMed, Oncoimmunology) - "In addition, SGT-53 alleviates a fatal xenogeneic hypersensitivity associated with the anti-PD1 antibody in this model. Our data suggest that restoring p53 function by SGT-53 is able to boost anti-tumor immunity to augment anti-PD1 therapy by sensitizing tumors otherwise insensitive to anti-PD1 immunotherapy while reducing immune-related adverse events."

Checkpoint inhibition • Journal • Biosimilar • Brain Cancer • Breast Cancer • Immune Modulation • Immunology • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

SGT-53 in Children With Recurrent or Progressive CNS Malignancies (clinicaltrials.gov) - P1; N=6; Not yet recruiting; Sponsor: SynerGene Therapeutics, Inc.; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date

Phase II Study of Combined Temozolomide and SGT-53 for Treatment of Recurrent Glioblastoma (clinicaltrials.gov) - P2; N=1; Terminated; Sponsor: SynerGene Therapeutics, Inc.; N=26 ➔ 1

Clinical • Enrollment change

Study of Combined SGT-53 Plus Gemcitabine/Nab-Paclitaxel for Metastatic Pancreatic Cancer (clinicaltrials.gov) - P2; N=28; Recruiting; Sponsor: SynerGene Therapeutics, Inc.; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2019 ➔ Dec 2020

Trial completion date • Trial primary completion date

A Study of SGT-53 in Children With Refractory or Recurrent Solid Tumors (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: SynerGene Therapeutics, Inc.; Trial completion date: Nov 2020 ➔ Nov 2021; Trial primary completion date: Nov 2019 ➔ Nov 2020

Clinical • Trial completion date • Trial primary completion date

A tumor-targeting nanomedicine carrying the p53 gene crosses the blood-brain barrier and enhances anti-PD-1 immunotherapy in mouse models of glioblastoma. (PubMed, Int J Cancer) - "Our data suggest that SGT-53 can boost antitumor immunity and sensitize glioblastoma to anti-PD-1 therapy by converting immunologically 'cold' tumors into 'hot' tumors. Combining SGT-53 with anti-PD-1 might benefit more patients from anti-PD-1 immunotherapy and our data support evaluation of this combination in patients with glioblastoma."

IO Biomarker • Journal • Preclinical

Immunotherapy plus gene therapy: A tumor-targeting nanomedicine carrying the TP53 gene crosses the blood–brain barrier and enhances anti-PD-1 immunotherapy in mouse models of glioblastoma (SITC 2019) - "Tumor-targeted p53 gene therapy via SGT-53 was able to augment anti-PD-1 immune checkpoint blockade and convert mouse syngeneic glioblastoma tumors that were unresponsive (immunologically "cold" tumors) into tumors that were more responsive to anti-PD-1 immunotherapy. These findings suggest that SGT-53 has potential to enhance the efficacy of checkpoint blockade and thereby provide for improved outcomes for patients with glioblastomas. Our observations provide compelling motivation to test the combination of SGT-53 and a checkpoint inhibitor in the context of a clinical trial for glioblastoma."

IO Biomarker • PD(L)-1 Biomarker • Preclinical

Phase II Study of Combined Temozolomide and SGT-53 for Treatment of Recurrent Glioblastoma (clinicaltrials.gov) - P2; N=26; Terminated; Sponsor: SynerGene Therapeutics, Inc.; Recruiting ➔ Terminated

Clinical • Trial termination

SGT-53 in Children With Recurrent or Progressive CNS Malignancies (clinicaltrials.gov) - P1; N=6; Not yet recruiting; Sponsor: SynerGene Therapeutics, Inc.; Trial completion date: Mar 2020 ➔ Dec 2021; Trial primary completion date: Sep 2019 ➔ Dec 2020

Clinical • Trial completion date • Trial primary completion date