QN-302 / Qualigen Therap - LARVOL DELTA

Cellular adaptations impact the biological activity of naphthalene diimide G-quadruplex ligands in ALT-positive osteosarcoma cells. (PubMed, Cell Death Dis) - "Here we have investigated the effects of two naphthalene diimide (NDI)-based G4 interacting agents (NMe2 and QN-302) in a pair of ALT-positive human osteosarcoma (U-2 OS and Saos-2) cell lines...This, in turn may impinge on the biological activity of G4 interacting agents. Deciphering these mechanisms and the associated molecular determinants will help accelerating the development of G4-based therapeutic interventions in ALT tumors."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Harnessing the impacts of a G-quadruplex ligand in liposarcoma: Implications for MDM2 oncogene targeting and DNA damage-mediated immunomodulatory effects (EACR 2025) - "We have identified a novel therapeutic strategy to inhibit MDM2 expression and promote p53 reactivation in DDLPS. Additionally, QN-302-induced DNA damage may activate the cGAS-STING pathway in DDLPS cell lines. The G4 multiple-target modality holds potential for further development through the rational design of drug combinations with standard chemotherapy, targeted therapies, and immunotherapy."

Immunomodulating • IO biomarker • Liposarcoma • Oncology • Sarcoma • Solid Tumor • CGAS • IFI27 • IL6 • MDM2

The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels. (PubMed, Nucleic Acids Res) - "In patient-derived xenograft mouse models, QN-302 treatment reduced tumour volume distribution and was well tolerated. We have identified a novel and effective therapeutic strategy to reduce MDM2 expression and promote p53 reactivation in tumours harbouring wild-type TP53, such as WD/DDLPSs."

Journal • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2 • TP53

The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels. (PubMed, Nucleic Acids Res) - "In patient-derived xenograft mouse models, QN-302 treatment reduced tumour volume distribution and was well tolerated. We have identified a novel and effective therapeutic strategy to reduce MDM2 expression and promote p53 reactivation in tumours harbouring wild-type TP53, such as WD/DDLPSs."

Journal • Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2 • TP53

A Phenotypic Approach to the Discovery of Potent G-Quadruplex Targeted Drugs. (PubMed, Molecules) - "The major genes whose expression has been down-regulated by QN-302 are presented here: all contain G4 propensity and have been found to be up-regulated in human pancreatic cancer. Some of these genes are also upregulated in other human cancers, supporting the hypothesis that QN-302 is a pan-G4 drug of potential utility beyond pancreatic cancer."

Journal • Review • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Structure-activity relationships for the pan-quadruplex experimental drug QN-302 and two analogs probed with comparative transcriptome profiling and molecular modeling (AACR 2024) - "The distinct pattern of genes affected by QN-302 is hypothesized to contribute to its superior potency compared to CM03 and SOP1247. Its superior ability to stabilize quadruplex structures has been attributed to its benzyl-pyrrolidine substituent fitting into and filling most of the space in a quadruplex groove compared to the hydrogen atom in CM03 or the methoxy group in SOP1247."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Characterization of the biological effects of a quadruplex-interacting molecule in dedifferentiated liposarcoma cells (AACR 2024) - "In the present study, the biological activity of a tetra-substituted naphthalene diimide (NDI) G4-L derivative (SOP1812/QN-302) has been characterized in two patient-derived DDLPS cell lines...These effects were paralleled by a 3-4 time increase in the number of γ-H2AX foci, the appearance of the cleaved form of PARP-1 and a pronounced inhibition of cell growth over time. Altogether, our findings indicate that targeting G4 structures by quadruplex-interacting molecules may represent a potential novel and effective therapeutic strategy in DDLPS."

Liposarcoma • Oncology • Sarcoma • Solid Tumor • MDM2

The pan-quadruplex drug QN-302 targets up-regulated genes in pancreatic cancer and in other cancer types and correlate with poor patient prognosis (AACR 2024) - "They are especially favored in colorectal, liver and renal cancers, suggesting that QN-302 may have anticancer effects in these cancers as well as in PDAC. We also do not exclude the strong possibility that each cancer type also has its own group of G-quadruplex containing genes that are sensitive to QN-302."

Clinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Kidney Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Renal Cell Carcinoma • Solid Tumor

Early clinical experience with a novel first-in-class G-quadruplex experimental anti-cancer drug (AACR 2024) - "They were also clinically observed to have improved QOL compared to prior SOC while on therapy with QN-302,This presentation will outline this unique approach and summarize safety, tolerability, PK/PD data and any early clinical data as described above including preliminary biomarker data now that clinical evaluation has commenced. The advantages and challenges of QN-302 will also be discussed."

Clinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

The pan-quadruplex drug QN-302 selectively down-regulates key pathway targets in pancreatic cancer cells that are up-regulated in human pancreatic cancer (AACR 2024) - "Data from a xenograft model for pancreatic cancer is also available for four of these genes, which concurs with the cellular data. We suggest that the identification of these 11 genes may also provide a basis for biomarker selection and possible patient stratification based on transcriptome data."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Qualigen Therapeutics Announces Poster Featuring Positive Early Clinical Experience with QN-302, a Novel First-in-Class G-Quadruplex Experimental Anti-Cancer Drug, at the American Association of Cancer Research (AACR) 2024 Annual Meeting (GlobeNewswire) - P1 | N=54 | NCT06086522 | Sponsor: Qualigen Theraputics, Inc | "Results demonstrated that for the first five patients (three of whom were PDAC patients), QN-302 is overall well-tolerated (no SAE) and they have reported a 'good' quality of life during the dosage period, with some early indications of stable PDAC disease. All PDAC patients had ultimately failed extensive prior therapy. Dose escalation initiated (patient #101-004) after three patients successfully completed cycle 1 of the initial dose. Dose escalation will be continued, with more patients being enrolled in the coming months....In addition, Qualigen presented three other posters on QN-302 at AACR..."

P1 data • Preclinical • Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Structure-activity relationships for the G-quadruplex-targeting experimental drug QN-302 and two analogues probed with comparative transcriptome profiling and molecular modeling. (PubMed, Sci Rep) - "This distinctive pattern of genes affected by QN-302 is hypothesized to contribute to its superior potency compared to CM03 and SOP1247. Its enhanced ability to stabilize G4 structures has been attributed to its benzyl-pyrrolidine substituent fitting into and filling most of the space in a G4 groove compared to the hydrogen atom in CM03 or the methoxy group substituent in SOP1247."

Journal • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

QN-302 demonstrates opposing effects between i-motif and G-quadruplex DNA structures in the promoter of the S100P gene. (PubMed, Org Biomol Chem) - "QN-302 exhibits exceptional combined synergistic effects compared to many other G-quadruplex and i-motif interacting compounds. This work further emphasises the importance of considering G-quadruplex and i-motif DNA structures as one dynamic system."

Journal • Oncology • S100P

Qualigen Therapeutics Announces First Patient Dosed in the Phase 1a Clinical Trial of QN-302 for Treatment of Advanced or Metastatic Solid Tumors (GlobeNewswire) - "Qualigen Therapeutics, Inc...announces today that the first patient in the Phase 1a clinical trial has been dosed with QN-302...designed for the treatment of advanced or metastatic solid tumors. The first clinical site is located at START Midwest in Grand Rapids, Michigan....Qualigen anticipates providing an update on safety and preliminary efficacy of the Phase 1a study in the first half of 2024."

P1 data • Trial status • Oncology • Solid Tumor

Trial to Evaluate Safety, PD & PK of IV Study Drug, QN-302, in Pts w/ Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Qualigen Theraputics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

A Phase I Trial Evaluating Safety, PD & PK of IV Study Medication, QN-302, in Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=54 | Not yet recruiting | Sponsor: Qualigen Theraputics, Inc.

Metastases • New P1 trial • Oncology • Solid Tumor

Qualigen Therapeutics Presents Scientific Data on QN-302 at AACR Special Conference: Pancreatic Cancer 2023 (GlobeNewswire) - "Qualigen Therapeutics, Inc...announces the presentation of two posters on the Company’s lead compound, QN-302, at the ninth American Academy of Cancer Research (AACR) Special Conference on Pancreatic Cancer, held September 27th to 30th at the Westin Copley Place in Boston....QN-302 and related chemical analogs CM03 and SOP1247 showed nanomolar potency in various cell lines, including gemcitabine-resistant MIA-PACA2 and PANC-1 cell lines, as well as significant G4 stability evident by low nanomolar binding affinity [ΔTm (°)] to G4s....QN-302 is a small molecule G4-selective transcription inhibitor in Phase 1 clinical development for the treatment of G4-expressing solid tumors, such as pancreatic cancer, prostate cancer, sarcomas, and others.....The Company anticipates the dosing of at least 24 patients in the Phase 1 trial can be completed by the end of 2024..."

New P1 trial • Preclinical • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Sarcoma

Qualigen Therapeutics Partners with TD2 for Phase 1 Clinical Development of QN-302 for the Treatment of Advanced or Metastatic Solid Tumors (GlobeNewswire) - "Qualigen Therapeutics, Inc...announced today it is partnering with Translational Drug Development (TD2) as the contract research organization (CRO) to conduct the Phase 1 clinical development of lead drug candidate QN-302."

Licensing / partnership • Oncology • Solid Tumor

Qualigen Therapeutics, Inc. Reports Financial Results and Corporate Update for Quarter Ending June 30, 2023 (GlobeNewswire) - "The $0.1 million increase in therapeutics research and development costs was primarily due to a $0.5 million increase in QN-302 pre-clinical research and development costs, offset by a decrease of pre-clinical research and development costs of $0.4 million for QN-247."

Commercial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Qualigen Therapeutics Announces US FDA IND Clearance to Initiate Phase 1 Clinical Trial of QN-302 for Treatment of Advanced or Metastatic Solid Tumors (GlobeNewswire) - "Qualigen Therapeutics...announces today that the U.S. Food and Drug Administration (FDA) has cleared the Company’s IND application for QN-302, a potential best-in-class small molecule G-Quadruplex (G4)-selective transcription inhibitor. Based on this clearance, the Company plans to initiate the Phase 1 clinical trial in the second half of 2023 and will enroll patients with advanced or metastatic solid tumors....The Company anticipates the dosing of at least 24 patients in the Phase 1 trial can be completed in 2024..."

IND • New P1 trial • Oncology • Solid Tumor

Qualigen Therapeutics, Inc. Reports Financial Results and Corporate Update for Quarter Ending March 31, 2023 (GlobeNewswire) - "Research and development costs increased from $1.9 million for the three months ended March 31, 2022 to $2.1 million for the three months ended March 31, 2023. Of the $2.1 million of research and development costs for the three months ended March 31, 2023, $1.3 million (60%) was attributable to therapeutics and $0.8 million (40%) was attributable to diagnostics....The decrease in therapeutics research and development costs was primarily due to a decrease of pre-clinical research and development costs of $0.6 million in QN-247 expenses, a decrease of $0.2 million in stock-based compensation expenses, a decrease in pan-RAS expenses of $0.1 million, offset by an increase in QN-302 pre-clinical research and development costs of $0.5 million."

Commercial • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

QLGN: IND for QN-302 to be Submitted in Mid-2023… (Yahoo Finance) - "Qualigen Therapeutics, Inc...is continuing work toward the submission of an Investigational New Drug (IND) application for its lead therapeutic program, QN-302. We anticipate an IND being filed for QN-302 in mid-2023....We look forward to Qualigen filing the IND for QN-302 such that a Phase 1 trial can initiate in the second half of 2023. We expect additional details regarding the Phase 1 trial to be released with news of acceptance of the IND along with preliminary timelines for that trial."

IND • New P1 trial • Oncology

The potent quadruplex-binding compound QN-302 shows anti-tumor activity as a monotherapy in an orthotopic in vivo model of pancreatic cancer (AACR 2023) - "A separate group of mice was treated with Gemcitabine twice weekly IV during this period, at a dosage of 15 mg/kg. This orthotopic model is the 4th in vivo study in a pancreatic cancer model showing anti-tumor activity for QN-302, further confirming the potential of this compound for human disease. QN-302 is currently in an advanced stage of pre-IND development by Qualigen Inc."

Monotherapy • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

The potent quadruplex-binding compound QN-302 down-regulates the S100P gene in in vitro and in vivo models of pancreatic cancer: a potential therapeutic target and biomarker for PDAC (AACR 2023) - "QN-302 is bio-available at therapeutic doses and is well tolerated at these levels in the animal models. It is being developed for clinical evaluation by Qualigen Therapeutics Inc and is currently at the pre-IND stage."

Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • S100P

Structure-based design rules for potent quadruplex-binding compounds based on the naphthalene diimide core (AACR 2023) - "This strongly implies that most of the contribution to ND-G4 affinity comes from the side chains, and especially from the protonated end groups. These and other observations have led us to develop a structure-activity framework for tetra-substituted NDs, which has culminated in their optimization and the design of QN-302, with enhanced cellular potency and G4 affinity compared to previous NDs."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor