Veyonda (idronoxil) / Noxopharm - LARVOL DELTA

Synthesis and biological evaluation of pyrano and furano fused ring isoflavene derivatives. (PubMed, RSC Adv) - "Idronoxil (IDX) is a clinically tested isoflavene with anticancer and anti-inflammatory activity. A selection of analogues with differing functionality was evaluated for anticancer activity across prostate (PC-3), neuroblastoma (SKN-BE(2)C), and triple-negative breast cancer (MDA-MB-231) cell lines. These findings establish synthetic strategies for the incorporation of various fused rings to isoflavene scaffolds and offer insights for structure-activity optimisation."

Journal • Breast Cancer • Neuroblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer

Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer (clinicaltrials.gov) - P1 | N=25 | Completed | Sponsor: Noxopharm Limited | Phase classification: P1b ➔ P1

Phase classification • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors (clinicaltrials.gov) - P1/2 | N=21 | Terminated | Sponsor: Noxopharm Limited | Phase classification: P1b/2a ➔ P1/2

Metastases • Phase classification • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • ER

Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection. (PubMed, Nat Commun) - "Treatment with idronoxil, or the small molecule inhibitor MRT67307, suppresses TBK1/IKKε signalling and attenuates cellular and molecular lung inflammation in SARS-CoV-2-challenged mice. Our findings additionally demonstrate that engagement of STING is not the major driver of these inflammatory responses and establish a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper-inflammation."

Journal • Preclinical • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • STING

A Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=10 | Terminated | Sponsor: Noxopharm Limited | Trial completion date: Aug 2023 ➔ May 2023 | Active, not recruiting ➔ Terminated; Slow recruitment

Trial completion date • Trial termination • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NPPB

A Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors (clinicaltrials.gov) - P1b/2a | N=21 | Terminated | Sponsor: Noxopharm Limited | Active, not recruiting ➔ Terminated; Slow Recruitment

Metastases • Trial termination • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • ER

A phase I/II trial of NOX66 in combination with nivolumab in patients (pts) with advanced cancer. (ASCO 2023) - "Background: NOX66 (idronoxil) targets ENOX2 and suppresses STING-mediated inflammatory pathways, reducing IFN and NFκB driven cytokine production by cancer cells. Preliminary analysis shows promising tumour responses from the combination therapy which appears to be well-tolerated, with no safety signals evident to date. Clinical trial information: ACTRN12621001537842."

Clinical • Combination therapy • Metastases • P1/2 data • Hepatology • Immunology • Myositis • Oncology • Pancreatic Cancer • Squamous Cell Carcinoma • CD4 • CD8 • NF-κβ • STING

A Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Noxopharm Limited | N=34 ➔ 10 | Trial primary completion date: Jul 2023 ➔ May 2023

Enrollment change • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NPPB

A Study of NOX66 Plus Doxorubicin in Anthracycline-naïve, Adult Patients With Soft Tissue Sarcoma (clinicaltrials.gov) - P1 | N=34 | Active, not recruiting | Sponsor: Noxopharm Limited | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Aug 2023 | Trial primary completion date: Jun 2024 ➔ Jul 2023

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • NPPB

A Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors (clinicaltrials.gov) - P1b/2a | N=21 | Active, not recruiting | Sponsor: Noxopharm Limited | Recruiting ➔ Active, not recruiting | N=70 ➔ 21 | Trial completion date: Feb 2024 ➔ Aug 2023

Enrollment change • Enrollment closed • Metastases • Trial completion date • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • ER

Noxopharm quits development of Veyonda, reduces headcount as stock plummets nearly 40% (Bioworld) - "Noxopharm Pty Ltd.’s stock plummeted nearly 40% on the morning of April 6 after the company announced it was quitting development of its lead program, Veyonda (idronoxil/formerly OX-66), shuttering its DARRT-2 and CEP-2 oncology clinical trials and disbanding its clinical trial team to contain costs."

Discontinued • Stock price • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Oncology • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

ENOX2 inhibition enhances infiltration of effector memory T-cell and mediates response to chemotherapy in immune-quiescent cancer. (PubMed, J Adv Res) - "Tumor-intrinsic ENOX2 expression is associated with tumor phenotype and PFS in NPC. Targeting ENOX2 with IDX and cisplatin impose qualitative control of T-cell response by preferentially increasing immune cells infiltration, Tem differentiation and tumor suppression. We suggest that ENOX2 inhibition may be a promising therapeutic strategy to enhance the effects of chemotherapy."

Journal • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • CD8

The role of isoflavones in augmenting the effects of radiotherapy. (PubMed, Front Oncol) - "Currently ongoing clinical research explores a potential of another significant isoflavone, idronoxil, also known as phenoxodiol, as radiation enhancing agent. This review discusses important aspects of the development of isoflavones as anticancer agents, and mechanisms potentially relevant to their activity in combination with radiation therapy of cancer. It gives a critical overview of studies characterizing isoflavone targets such as topoisomerases, ENOX2/PMET, tyrosine kinases and ER receptor signaling, and cellular effects on the cell cycle, DNA damage, cell death, and immune responses."

Journal • Review • Cardiovascular • Genito-urinary Cancer • Heart Failure • Oncology • Prostate Cancer • Solid Tumor

Quantifying molecular imaging patterns of treatment response or progression using a novel traffic light workflow within a prospective phase I/II trial of 177LuPSMA-617 and NOX66 (LuPIN). (ASCO-GU 2022) - " 56 men with mCRPC previously treated with taxane chemotherapy and androgen signaling inhibitor were enrolled, receiving up to 6 doses of LuPSMA and a radiation sensitizer idronoxil (NOX66). This study demonstrates the feasibility of characterizing lesional response on molecular imaging with a quantification TL workflow. TL workflow response independently correlated with survival outcomes, indicating serial PSMA PET has prognostic biomarker potential."

Clinical • P1/2 data • Genito-urinary Cancer • Prostate Cancer

[VIRTUAL] Updated results of a phase I/II prospective dose escalation trial evaluating safety and efficacy of combination 177Lu PSMA 617 and idronoxil in men with mCRPC post androgen signalling inhibition and taxane chemotherapy (LuPIN trial). (ASCO 2020) - "Background: There is no established standard of care post cabazitaxel in men with mCRPC. Combination LuPSMA-617 + NOX 66 appears safe and efficacious in men with heavily pre-treated end stage mCRPC. Research Funding: Noxopharm"

Clinical • P1/2 data • Oncology • Pain • FDG PET

A Study of NOX66 and External Beam Radiotherapy in Patients With Metastatic Castration-resistant Prostate Cancer and Other Solid Tumors (clinicaltrials.gov) - P1b/2a | N=70 | Recruiting | Sponsor: Noxopharm Limited | N=100 ➔ 70 | Trial primary completion date: Oct 2022 ➔ Aug 2023

Enrollment change • Metastases • Trial primary completion date • Breast Cancer • Genito-urinary Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • ER

Noxopharm set for busy six months ahead with strong news flow expected from drug pipeline (Investing.com) - "In the next six months, the company is looking forward to the start of patient recruitment for its IONIC-1 (checkpoint inhibitor therapy), DARRT-2 (radiotherapy) and CEP-2 (chemotherapy) programs for its Veyonda® anti-cancer drug candidate....This week NOX secured Investigational New Drug (IND) approval from the US Food and Drug Administration (FDA) for its DARRT-2 multi-national clinical study, paving the way for the trial to kick off in the United States. The green light marks the second IND classification granted to cover the administration of Noxopharm’s anti-cancer drug candidate, Veyonda®, in US cancer patients."

IND • Trial status • Breast Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

Noxopharm Advances to the Efficacy Portion of its Phase 2 Prostate Cancer Trial (Market Screener) - "Noxopharm... advanced to the efficacy portion of its phase 2 trial evaluating the use of the drug candidate Veyonda in combination with low-dose external beam radiotherapy to treat prostate cancer. The move was made following the safety data from the last dose cohort for the study, which showed that Veyonda was safe at a 1,600-milligram dose, the pharmaceutical firm said on Tuesday."

Trial status • Genito-urinary Cancer • Oncology • Prostate Cancer

Results of a phase I/II prospective dose-escalation trial evaluating safety and efficacy of combination 177LuPSMA-617 and NOX66 in men with mCRPC post androgen signalling inhibition and two lines of taxane chemotherapy (LuPIN trial). (ASCO-GU 2020) - " 32/43 (26% imaging screen failures) screened men were enrolled (November 2017 – June 2019), of whom 100% had prior docetaxel and ASI, and 94% (30/32) cabazitaxel... Combination 177LuPSMA-617 with NOX66 appears safe and efficacious in men with heavily pre-treated mCRPC. Clinical trial information: ACTRN12618001073291. Research Funding: Noxopharm Pty Ltd., St Vincent's Hospital Clinical trials"

Clinical • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • FDG PET

Evaluation of Lu-PSMA SPECT Quantitation as a Response Biomarker within a Prospective Lu-PSMA-617 and NOX66 Combination Trial (LuPIN). (PubMed, J Nucl Med) - "In the patients with SPECT-TTV progression at week-12, 50% (5/10) had no concurrent PSA progression (median PSA-PFS 4.5 months (95% CI 2.8-5.6), and 5/10 men had both PSA and SPECT TTV progression at week 12 (median PSA-PFS 2.8 months (95% CI 1.8-3.7). Increasing PSMA-TTV on quantitative Lu-SPECT/CT predicts short progression free survival and may play a future role as an imaging response biomarker."

Biomarker • Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

LuPIN Substudy of Posttreatment PET after Lu-PSMA-617 with NOX66: Prognostic Value of FDG and PSMA. (PubMed, Radiol Imaging Cancer) - No abstract available

Journal

The prognostic value of post-treatment PSMA and FDG PET/CT in metastatic, castration-resistant prostate cancer treated with LuPSMA-617 and NOX66 in a phase I/II trial (LuPIN). (PubMed, J Nucl Med) - " Change in quantitative PSMA-TTV has strong potential as a prognostic biomarker with LuPSMA-617 therapy, independent of FDG-PET parameters, PSA or radiographic progression. Further research into the value of post-treatment PET as imaging biomarker is warranted."

FDG PET • Journal • P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Isoflavonoid-based therapeutics to remodel immunologically cold tumors in nasopharyngeal carcinoma. (ASCO 2022) - "We aimed at delineating and defining the contribution of idronoxil (IDX), a synthetic flavonoid derivative, in restoring sensitivity to apoptosis and potentially modulating the immune microenvironment of NPC...In vitro, we observed increased migration of T cells towards cancer cells when tumor cells were pre-treated with the combination of IDX and cisplatin (IDX+Cis) compared with monotherapy (IDX or cis alone) or untreated... Distinct immunospatial profiles could be associated with clinicopathologic characteristics. The ability of IDX to modulate T cell populations indicates the potential of IDX to enhance the efficacy of current chemotherapy treatments in NPC by upregulating cellular trafficking toward tumor."

Immunology • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • CD8

Noxopharm achieves abscopal responses in prostate cancer (Businesswire) - P1, N=26; DARRT-1 (NCT03307629); Sponsor: Noxopharm Limited; "Noxopharm...has announced the details of the radiographic review of its DARRT-1 clinical study and is pleased to report a 27% incidence of abscopal response in soft tissue lesions using a combination of Veyonda® and low-dose radiotherapy.

P1 data • Genito-urinary Cancer • Oncology • Prostate Cancer

Combo of 177Lu-PSMA-617 and novel radiosensitizer effective in mCRPC (Urology Times) - P1/2 | N=56 | "Combination treatment with the investigational radiosensitizer idronoxil (NOX66) and the FDA-approved targeted radioligand therapy 177Lu-PSMA-617 (Lu 177 vipivotide tetraxetan; Pluvicto) showed promising safety and efficacy in patients with heavily pre-treated metastatic castration-resistant prostate cancer...the novel radionuclide combination induced a ≥50% PSA decline in more than 60% of the patients treated. The median overall (OS) survival was 19.7 months....The median patient follow-up was 21.8 months. Across the population 86% of patients experienced at least some decline in their PSA level. Additionally, 34 (61%) patients had a PSA decline ≥50%. The median PSA progression-free survival was 7.5 months."

P1/2 data • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor