Idronoxil - Kazia Therapeutics/Noxopharm
Alternative Names: NOX-66; VeyondaLatest Information Update: 28 Oct 2023
At a glance
- Originator Noxopharm
- Developer Children Cancer Institute; Kazia Therapeutics; Noxopharm
- Class Anti-infectives; Anti-inflammatories; Antineoplastics; Antivirals; Hormones; Isoflavones; Small molecules
- Mechanism of Action 1 Phosphatidylinositol 3 kinase inhibitors; Cyclin-dependent kinase inhibitors; MPYS protein inhibitors; Sphingosine kinase inhibitors; Src-Family kinase modulators; TBK1 protein inhibitors; Tumour-associated NADH oxidase inhibitors
-
Orphan Drug Status
Yes - Soft tissue sarcoma
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- Phase II Solid tumours
- Phase I/II Prostate cancer
- Phase I Soft tissue sarcoma
- Preclinical Nasopharyngeal cancer; SARS-CoV-2 sepsis
- Research Influenza virus infections
- No development reported COVID 2019 infections; Diffuse intrinsic pontine glioma
Most Recent Events
- 28 Oct 2023 No recent reports of development identified for phase-I development in COVID-2019-infections in Moldova (Rectal, Suppository)
- 28 Aug 2023 No recent reports of development identified for phase-I development in Prostate-cancer(Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Georgia (Rectal, Suppository)
- 28 Aug 2023 No recent reports of development identified for phase-I development in Prostate-cancer(Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in New Zealand (Rectal, Suppository)
Development Overview
Introduction
An innovative formulation of idronoxil, is being developed by Kazia Therapeutics (previously Noxopharm) and Noxopharm for the treatment of drug-resistance in cancer chemotherapy and septic shock associated with COVID-2019 infections. Idronoxil is a small molecule, specifically binds to and inhibits the activity of tumour-specific external NADH oxidase 2 (ENOX2; tumour-associated NADH oxidase). The ENOX2 protein is responsible for maintaining the transmembrane electron potential in the cancer cell's plasma membrane. When ENOX2 is inhibited by idronoxil, it renders the cell highly vulnerable to damage by chemotherapy and radiotherapy. By inhibiting cyclin dependent kinases, idronoxil inhibit cancer cells division and arrest them in G2M phase which make the cell's DNA more susceptible to damage by radiation. By inhibiting sphingosine kinase and 1-Phosphatidylinositol-3-kinase, idronoxil blocks DNA-repair enzymes, PARP-1 and topoisomerase 1 and 2 and inhibits the ability of the cancer cell to repair its damaged DNA. Idronoxil also modulate the src family of kinases which regulate the role of spleen tyrosine kinase (SyK) and activate the immune cells particularly natural killer (NK) cells. Idronoxil has two main drug actions – a moderating effect on the ceramide/sphingosine-1-phosphate balance and inhibition of STING signaling reducing IFN and NFκB driven cytokine production by cancer cells. Activity against the former target contributes to its dual-acting oncotoxic and immuno-oncology functions designed to enhance the effectiveness and safety of standard oncology treatments. Activity against the latter target provides an anti-inflammatory effect, also contributing to an anti-cancer action, but also potentially blocking septic shock. Clinical development for prostate cancer and solid tumours is underway in the US, Australia, Georgia and New Zealand. Clinical development for SARS-CoV-2 sepsis is underway in Australia. Clinical development is underway in COVID-2019 infections in Moldova. Clinical development for soft tissue sarcoma is underway in the US. Preclinical development SARS-CoV-2 sepsis and nasopharyngeal cancer, diffuse intrinsic pontine glioma is underway in Australia. Early research is underway for influenza virus infections in Australia.
Noxopharm intends to develop idronoxil as a radio-enhancer in the treatment of both primary and secondary brain cancers in adults and children [1] .
Human studies using idronoxil administered in oral and intravenous dosage forms have shown that the drug is highly susceptible to phase II metabolism, resulting in loss of bio-activity. NOX 66 is a new dosage formulation of idronoxil developed specifically to protect the drug from phase II metabolism and ensuring the retention of the majority of administered drug in a bio-active form.
Idronoxil (NOX 66) has emerged from Noxopharm's research programme of isoflavonoid based cancer therapeutics [see Adis Insight Drug profile 800046244].
As at August 2023, no recent reports of development had been identified for phase-I development in Prostate-cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in New Zealand (Rectal, Suppository), Georgia (Rectal, Suppository), preclinical development in Diffuse intrinsic pontine glioma in Australia.
As at October 2023, no recent reports of development had been identified for phase-I development in COVID-2019-infections in Moldova (Rectal, Suppository).
Company Agreements
In December 2017, Kazia Therapeutics entered into a collaboration agreement with Noxopharm, to support the future development of idronoxil novel formulation (NOX 66). Under the terms of the collaboration, Kazia will provide certain technical and proprietary information to assist and expedite the successful development of idronoxil novel formulation. In return, Kazia will take a small equity interest in Noxopharm, to align the future interests of both companies. In January 2018, Kazia reported that it released Noxopharm from any claims of ownership associated with idronoxil novel formulation or the intellectual property and technology related to the formulation. The value of this assurance in terms of the shares was agreed to be a cap of 4.9% of the capital structure of Noxopharm over the next two years, with that equity escrowed for the next six months. There were no other ongoing payments such as milestones, licence fees, royalties associated with the agreement [2] [3]
Key Development Milestones
COVID-2019 infections
In August 2021, Noxopharm completed a phase I dose escalation and dose expansion NOXCOVID trial that evaluated idronoxil for the treatment of COVID-2019 infections (NOX66-007; NCT04555213). The open label trial was initiated in September 2020 and enrolled 40 patients in Moldova [4] .
In September 2020, Noxopharm initiated a phase I dose escalation and dose expansion NOXCOVID trial to evaluate idronoxil for the treatment of COVID-2019 infections. The open label trial intends to enroll 40 patients in Moldova (NOX66-007; NCT04555213) [4] . As of March 2021, Noxopharm initiated enrollment in part 2 of the study [5] . In April 2021, Noxopharm released data for a cohort of 18 patients with moderately severe cases of COVID-2019 infections, from the trial [6] [7] . In August 2021, the company released preliminary results from the trial [8] .
In August 2021, Noxopharm released preclinical data demonstrating anti-inflammatory response of idronoxil [9] .
Glioma
In preclinical studies, idronoxil killed cancer cells in primary cell cultures, established by Children’s Cancer Institute, from diffuse intrinsic pontine glioma (DIPG) tumours. Additionally, the drug was able to sensitise the cells to radiation, thereby leading to a significantly higher cancer cell death, along with a constant dose of radiation [1] .
Prostate cancer
In June 2023, Noxopharm terminates a phase I/II trial of idronoxil and external beam radiotherapy in patients with metastatic castration-resistant prostate cancer and other solid tumours due to slow recruitment (NCT04957290; NOX66-005). The open label trial was initiated in October 2021 and intended to enroll 21 patients in the USA and Hungary [10] .
As of August 2021, Noxopharm completed the phase I/II LuPin trial to determine the efficacy and safety of two doses of idronoxil (400 and 800 mg), in combination with 177 Lutetium PSMA 617 (radiotherapy) [see Adis Insight RDI Profile 800050453], in PSMA-positive patients with metastatic castrate-resistant prostate cancer (374100; HREC17SVH19; U1111-1206-1132; ACTRN12618001073291l LuPIN-1). The internally-delivered radiotherapy 177 Lu PSMA 617 is administered in up to six monthly cycles, each cycle comprising a single intravenous injection of 177 Lu PSMA 617 followed by 10 days of idronoxil treatment. The open label, non-randomised, pilot study initiated in April 2018 and enrolled 56 males in Australia [11] [12] [13] [14] . The first eight patients received 400 mg of Veyonda daily on days 1-10 of each cycle. Following a safety data review, the dose for patients 9-16 was escalated to 800 mg of Veyonda [15] . In September 2018, Noxopharm announced that the phase I LuPIN study has been granted approval for increasing the patient numbers from 16 to 32 males. Both treatment regimens of idronoxil (400 and 800 mg), in combination with radiotherapy was shown to be well tolerated [16] . In May 2019, interim efficacy and safety data from the trial were released by Noxopharm [17] . In September 2019, and February 2020, company released results from the study. The company also reported initiation of dosing of 1200mg dosage of idronoxil in combination with 177 Lutetium PSMA 617 in 24 patients [18] [19] [20] . In May 2020, efficacy and safety results from the trial were presented at 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020) [21] . Updated data from the trial were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-2021) [22]
In February 2020, Noxopharm in collaboration with GenesisCare intends to provide the combination of idronoxil 177 Lutetium and PSMA 617 (radiotherapy) under a compassionate use program in Australia to patients with advanced, treatment resistant, metastatic prostate cancer (mCRPC) being treated with theranostics [23] [24] . In March 2018, Noxopharm released results from two clinical cases which were received as part of a compassionate use outside of the company's formal clinical trial programme [25] .
In January 2019, Noxopharm completed a first-in-man phase Ib/IIa CEP-1 trial evaluating the safety and activity of idronoxil monotherapy and combination therapy with carboplatin, in patients with refractory solid tumours including progressive, late-stage breast, ovarian, lung or prostate cancer that are non-responsive to standard therapies (CEP-1; NOX66-001A; NCT02941523). The two part, open-label, dose escalation study was initiated in March 2017 and had enrolled 19 adult and elderly patients Georgia. The phase IIa part of study will be initiated based on results from the phase Ia/Ib part of the trial [26] [27] . In March 2018, Noxopharm presented the safety and efficacy results from the phase Ib part of the trial at European Society for Medical Oncology Congress (ESMO-2018) [28] . In June 2018, the company presented interim results at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018) [29] . In November 2018, Noxopharm released final data from the phase Ib portion of the trial [30] .
Noxopharm initiated the DARRT (enhancement of external beam radiotherapy) and LUPIN (enhancement of intravenous brachytherapy radiotherapy) clinical programmes of idronoxil (NOX 66), in combination with radiotherapy, for late stage prostate cancer. The DARRT program is Direct and Abscopal Response to Radiotherapy, and related to the use of idronoxil to enhance the known abilities of radiotherapy both to kill cancer cells directly exposed to radiation (direct response), and to result in the death of cancer cells outside of the field of radiation (abscopal response). The DARRT programme involves a phase Ib DARRT-1 study and a second DARRT-2 study, a phase II study in 80 patients with solid tumours [31] [25] [14] . In January 2023, Noxopharm Limited announced the DARRT-2 Safety Steering Committee found that the third cohort of patients treated with a 1600 mg dose of idronoxil (Veyonda®) to be safe. No further dose escalations are planned [32] .
In September 2020, Noxopharm completed a proof-of-concept phase Ib DARRT-1 (Direct and Abscopal Response to Radiotherapy- 1) trial that investigated the efficacy, safety and tolerability of idronoxil, in combination with palliative dose of radiation therapy, in patients with metastatic castrate-resistant prostate cancer (NOX66-002A; NCT03307629). In December 2019, Noxopharm announced that phase Ib DARRT-1 has achieved its primary and secondary endpoints of safety with no significant dose limiting toxicity and efficacy respectively were met. The open label, non-randomised trial was initiated in November 2017 and enrolled 26 patients in Australia, New Zealand and Georgia [33] [25] [14] [13] [34] . In July 2018, the company released interim safety data [35] [36] [37] . Subsequently topline results were released. Safety and efficacy results were presented by the company in December 2019 [38] [39] [40] [41] [42] .
In May 2020, Noxopharm completed a phase I trial that evaluated the safety and absorption of a new formulation of idronoxil in healthy volunteers (NOX66-006; 378739; 2019-09-824; ACTRN12620000002987). The open label trial was initiated in November 2019 and enrolled 24 volunteers in Australia [43] .
In August 2021, Noxopharm announced that, idronoxil in combination with 177lutetium-PSMA-617 (LuPSMA) demonstrated potent ability to enhance the cancer killing LuPSMA treatment in mice bearing human prostate cancer xenografts. The combination was exhibited an impressive synergistic therapeutic response, with sustained and almost complete regression of the tumor and minimally observed systemic toxicity [11] .
SARS-CoV-2 sepsis
In preclinical studies, established by Hudson Institute of Medical Research in Melbourne, idronoxil inhibited a range of inflammatory mediators known as cytokines, including interleukin-6 (IL-6), involved in a cytokine response syndrome (or cytokine storm) [44] .
Soft tissue sarcomas
In March 2022, the US FDA granted Orphan Drug Designation (ODD) to idronoxil (Veyonda®) for the treatment of soft tissue sarcoma [45] .
In June 2023, Noxopharm terminated a phase I CEP-2 trial due to slow recruitment. The trial was designed to study of idronoxil given rectally, in cohorts of patients with metastatic soft tissue sarcoma (STS) who have not been exposed to anthracycline therapy, using a fixed dose-escalation schema every 21 days to establish the maximum tolerated dose (MTD) of the combination of idronoxil and doxorubicin (NCT05100628; NOX66-004). The open-label, dose-escalation and dose-expansion trial was initiated in February 2022 and enrolled 10 patients in the US [46] . In April 2023, Noxopharm announced discontinuation of phase I CEP-2 trial to prioritise the other development. In November 2022, Safety Steering Committee reviewed the safety data from the second cohort of patients and found that 1200 mg dose was safe and well tolerated. Enrolment of the next cohort of patients for treatment with an increased dose of 1800 mg is now underway [47] .
Earlier in February 2020, Noxopharm announced that the US FDA has approved IND application for clinical study of idronoxil in combination with doxorubicin in patients with soft tissue sarcomas [48] .
Nasopharyngeal carcinoma: In May 2020, preclinical data from 2D and 3D nasopharyngeal carcinoma on treatment with idronoxil compared with cisplatin was presented at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020). In preclinical studies, NOX66 restored sensitivity to apoptosis and potentially modulate the immune microenvironment of nasopharyngeal carcinoma (NPC) [49] [50] .
Preclinical study confirms that idronoxil activates cancer-fighting immune cells and then enable their entry into microtumours [51] .
Solid tumors
In April 2023, NoxopharmIn announced discontinuation of phase II DARRT- 2 trial to prioritise the other development. Earlier in November 2021, Noxopharm initiated the phase II DARRT-2 study of idronoxil in combination with radiotherapy in patients with solid tumors. The multinational study is expected to enroll approximately 200 patients in the US and may extend to North America, Europe, and Australia [52] [25] [14] [53] [31] .
In October 2021, Noxopharm initiated a phase-I/II trial Immuno-Oncology with Veyonda® in Combination (IONIC) trial of idronoxil in combination with Opdivo®(nivolumab) in patients with solid tumours (ACTRN12621001537842;NOX66IS002). The open label, non-randomised trial intends to enrol 30 pateints in Australia [54] [47] . In June 2023, efficacy and safety data from the trial were presented at the 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) [55] .
NIO sponsored trials
Royal North Shore Hospital initiated a phase I trial in August 2017, to assess the safety and clinical tumour response of idronoxil suppository in combination with palliative radiotherapy for metastatic prostate cancer (NOX66 version 1; NCT03041285). The open-label, sequential trial will recruit approximately 12 patients in Australia [56] .
Financing information
In February 2020, Noxopharm raised $US8 million through capital raising, comprised of a $US3.1 million equity placement and a $US5 million loan. The proceeds will be utilised to advance the development of clinical trials of idronoxil, including the planned phase II DARRT-2 trial [57] .
Noxopharm, in July 2019, secured a funding facility for up to AU$26 million. The facility comprises an AU$4 560 000 (face value) secured convertible security (with 6-month lock-up) and up to AU$22 200 000 in ordinary share placements over a 12-month period. The company intends to utilise the proceeds from the financing for expanding the clinical development of idronoxil into CEP-2, DARRT-2 and immuno-oncology clinical trials, to meet ongoing working capital needs [58] .
In August 2016, Noxopharm completed an initial public offering $AUS6 million, and the company intends to use the funding to conduct clinical trials of idronoxil [59] [26] .
Patent Information
In Early 2023, United States patent office granted patent for isoflavonoid composition with improved pharmacokinetics [47] .
In November 2021, Noxopharm announced an intension for patents application for idronoxil in combination with radiotherapy starting with the allowance of claims by the US Patent Office [52] .
In April 2021, Noxopharm announced an international patent application aimed at protecting the use of idronoxil in blocking the development of septic shock associated with infections such as COVID-19 and influenza viruses [60] .
Kazia Therapeutics has intellectual property protection for idronoxil novel formulation [2] .
The family of PCT patents relating to NOX 66 DARRT have proceeded into the national examination phase in upwards of 80 countries [40] .
Drug Properties & Chemical Synopsis
- Route of administration Rectal
- Formulation Suppository, unspecified
- Class Anti-infectives, Anti-inflammatories, Antineoplastics, Antivirals, Hormones, Isoflavones, Small molecules
- Target 1 Phosphatidylinositol 3 kinase; Cyclin-dependent kinase; MPYS protein; Sphingosine kinase; Src-Family kinase; TBK1 protein; Tumour-associated NADH oxidase
- Mechanism of Action 1 Phosphatidylinositol 3 kinase inhibitors; Cyclin-dependent kinase inhibitors; MPYS protein inhibitors; Sphingosine kinase inhibitors; Src-Family kinase modulators; TBK1 protein inhibitors; Tumour-associated NADH oxidase inhibitors
-
WHO ATC code
J05A-X (Other antivirals)
L01 (Antineoplastic Agents)
-
EPhMRA code
J5B9 (Antivirals, others)
L1 (Antineoplastics)
- Chemical name 3-(4-Hydroxyphenyl)-2H-1-benzopyran-7-ol
- Molecular formula C15 H12 O3
- SMILES C1C(=CC2C=CC(=CC=2O1)O)C1C=CC(=CC=1)O
-
Chemical Structure
- CAS Registry Number 81267-65-4
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
advanced breast cancer |
Eligibility Criteria |
Testosterone PGR Estrogen receptor alpha (ER alpha) |
|
|
advanced breast cancer |
Outcome Measure |
PSA |
|
|
fallopian tube cancer |
Eligibility Criteria |
CA125 ovarian cancer antigen (MUC16) Alkaline phosphatase (ALPL) |
|
|
fallopian tube cancer |
Outcome Measure |
ecto-NOX disulfide-thiol exchanger 2 CA125 ovarian cancer antigen (MUC16) |
|
|
male breast cancer |
Eligibility Criteria |
Testosterone PGR Estrogen receptor alpha (ER alpha) |
|
|
male breast cancer |
Outcome Measure |
PSA |
|
|
non-small cell lung cancer |
Eligibility Criteria |
Testosterone PGR Estrogen receptor alpha (ER alpha) |
|
|
non-small cell lung cancer |
Outcome Measure |
PSA |
|
|
ovarian cancer |
Eligibility Criteria |
CA125 ovarian cancer antigen (MUC16) Alkaline phosphatase (ALPL) |
|
|
ovarian cancer |
Outcome Measure |
ecto-NOX disulfide-thiol exchanger 2 CA125 ovarian cancer antigen (MUC16) |
|
|
peritoneal cancer |
Eligibility Criteria |
CA125 ovarian cancer antigen (MUC16) Alkaline phosphatase (ALPL) |
|
|
peritoneal cancer |
Outcome Measure |
ecto-NOX disulfide-thiol exchanger 2 CA125 ovarian cancer antigen (MUC16) |
|
|
prostate cancer |
Brief Summary |
PSA |
|
|
prostate cancer |
Detailed Description |
folate hydrolase (prostate-specific membrane antigen) 1 |
|
|
prostate cancer |
Eligibility Criteria |
Testosterone PSA PGR Gonadotropin releasing hormone Estrogen receptor alpha (ER alpha) |
|
|
prostate cancer |
Outcome Measure |
PSA folate hydrolase (prostate-specific membrane antigen) 1 |
|
|
soft tissue sarcoma |
Official Title |
centrosomal protein 250 CDC42 effector protein 2 |
|
|
soft tissue sarcoma |
Outcome Measure |
Cardiac Troponin I BNP |
|
|
solid tumours |
Eligibility Criteria |
Testosterone PGR Estrogen receptor alpha (ER alpha) Bilirubin |
|
|
solid tumours |
Outcome Measure |
PSA |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Idronoxil - Kazia Therapeutics/Noxopharm | BNP | Outcome Measure |
| Cardiac Troponin I | Outcome Measure | |
| CDC42 effector protein 2 | Official Title | |
| centrosomal protein 250 | Official Title | |
| Estrogen receptor alpha (ER alpha) | Eligibility Criteria | |
| folate hydrolase (prostate-specific membrane antigen) 1 | Detailed Description, Outcome Measure | |
| PGR | Eligibility Criteria | |
| PSA | Eligibility Criteria, Outcome Measure | |
| Testosterone | Eligibility Criteria |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| COVID 2019 infections | in hospitalised patients with moderate systemic illness and who ate at high risk of developing severe sepsis /septic shock. | - | No development reported (I) | Moldova | Rectal / Suppository | Noxopharm | 28 Oct 2023 |
| Diffuse intrinsic pontine glioma | In children | - | No development reported (Preclinical) | Australia | unspecified / unspecified | Children Cancer Institute, Kazia Therapeutics | 28 Aug 2023 |
| Influenza virus infections | sepsis in Inluenza patients | - | Research | Australia | unspecified / unspecified | Noxopharm | 14 Apr 2021 |
| Nasopharyngeal cancer | - | - | Preclinical | Australia | unspecified / unspecified | Noxopharm | 07 Apr 2020 |
| Prostate cancer | Metastatic Castration-resistant Prostate Cancer | Late-stage disease, Metastatic disease, Second-line therapy or greater | Phase I/II | USA | Rectal / Suppository | Noxopharm | 11 Oct 2021 |
| Prostate cancer | in combination with radiotherapy | Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater | Phase I/II | Australia | Rectal / Suppository | Kazia Therapeutics | 31 Aug 2017 |
| Prostate cancer | in combination with radiotherapy in combination with radiation therapy | Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater | No development reported (I) | Georgia, New Zealand | Rectal / Suppository | Kazia Therapeutics | 28 Aug 2023 |
| SARS-CoV-2 sepsis | associated with COVID-2019 infections | - | Preclinical | Australia | Rectal / Suppository | Noxopharm | 02 Apr 2020 |
| Soft tissue sarcoma | - | Combination therapy | Phase I | USA | Rectal / Suppository | Noxopharm | 17 Jan 2022 |
| Solid tumours | - | - | Phase II | USA | unspecified / unspecified | Noxopharm | 10 Nov 2021 |
| Solid tumours | - | Late-stage disease, Monotherapy, Refractory metastatic disease, Second-line therapy or greater | Phase I/II | Georgia | unspecified / unspecified | Kazia Therapeutics | 03 Mar 2017 |
| Solid tumours | in combination with Carboplatin | Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater | Phase I/II | Georgia | unspecified / unspecified | Kazia Therapeutics | 03 Mar 2017 |
| Solid tumours | - | Late-stage disease, Metastatic disease, Second-line therapy or greater | Phase I/II | USA | Rectal / Suppository | Noxopharm | 11 Oct 2021 |
| Solid tumours | in combination with The Opdivo® (nivolumab) | Combination therapy, Second-line therapy or greater | Phase I | Australia | Rectal / Suppository | Noxopharm | 31 Oct 2021 |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Soft tissue sarcoma | - | USA | Noxopharm | 29 Mar 2022 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Noxopharm | Originator | Australia |
| Kazia Therapeutics | Owner | Australia |
| Royal North Shore Hospital | Collaborator | Australia |
| Children Cancer Institute | Collaborator | Australia |
| The Hudson Institute of Medical Research | Collaborator | Australia |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| Veyonda | Noxopharm | Solid tumours, Soft tissue sarcoma | Australia, USA |
Scientific Summary
Adverse Events
In the first-in-man phase Ib/IIa CEP-1 trial in patients (n=19) with solid tumours, idronoxil was well tolerated as monotherapy. One patient in monotherapy arm reported with anaemia which was related to idronoxil treatment. In combination with carboplatin, idronoxil at 400mg and 800mg did not exacerbate carboplatin toxicity. Overall, 83% of patients reported one or more AEs of which, 95% AEs were reported in combination arm. The frequent AEs reported were anaemia, neutropenia and hypocalcaemia, of which 80% AEs were due to carboplatin. One patient in combination arm showed hypersensitivity to carboplatin at initial injection [30] . In interim data, four SAEs, including three deaths were reported, but none were considered related to idronoxil [29] . Serious toxicity was noted in one of 15 patient, who was withdrawn from trial due to allergic reaction to carbolatin [28] [27] .
Solid tumours
Phase I/II
Preliminary data from the phase I/II IONIC trial of idronoxil nivolumab combination therapy appeared to be well-tolerated, with no safety signals evident in patients with advanced cancer. The most common adverse events was local perineal irritation, readily managed with topical corticosteroid cream. Two patients developed an erythematous rash over the trunk and limbs after 2 cycles, suspected to be related to the combination treatment. Five patients showed disease progression and 1 patient was withdrawn due to suspected immune mediated myositis and hepatitis resulting from nivolumab and was not evaluable. The open label, non-randomised trial enrolled 11 patients [55] [54] .
In updated results from the phaseIb DARRT-1 trial combination of low-dose (20Gy) palliative radiotherapy and idronoxil was well tolerated and showed no new adverse safety signals at the end of six month of the trial. None of the 21 grade ≥3 TEAEs were considered related to treatment. 9 patients had withdrawn, died or been lost to follow-up. Treatment with NOX 66, in combination with radiotherapy was well tolerated, led to occurrence of grade 1 adverse events (AEs), dry mouth, mucositis oral, fatigue, in 9 patients with prostate cancer. The AEs were deemed to be related to NOX 66 therapy. No drug-related toxicity were reported. The open-label, phase Ib DARRT-1 trial enrolled 25 patients [38] [40] [36] [35] [33] .
Updated results from the phase I/II trial demonstrated that idronoxil in combination with lutetium-177 PSMA 617 was generally safe and no dose limiting toxicities were reported. Earlier interim data from the trial reported that combination was well tolerated. However, one case of pneumonitis was reported in combination arm [20] [17] [12] [21] .
In a phase I NOXCOVID trial, no major safety issues were identified and 37 of 38 patients hospitalised with moderate respiratory disease were recovered [8] [4] .
Pharmacodynamics
Summary
Clinical studies:
In a clinical study involving a 68-year old man with metastatic, castrate-resistant prostate cancer involving secondary tumours in bone and soft tissue , administration of idronoxil novel formulation combined with radiotherapy led to complete disappearance of irradiated tumours and the absence of any other visible tumours in the body. PSA levels (a blood marker of prostate cancer load) were normalised and the patient remained 3.8 years later in complete remission with undetectable PSA levels with no further requirement of treatment in that time. This was a complete abscopal response. In another clinical study involving a 70-year old woman with leiomyosarcoma, administration of idronoxil novel formulation combined with doxorubicin treatment had no effect, with a slight increase in the size of the lung metastases under observation. Subsequently, following a course of palliative radiotherapy to the primary tumour in the presence of idronoxil novel formulation, a significant reduction in the size of the lung metastases was observed, with the patient’s cough resolving, within one month of treatment. Six months later, the primary tumour was stable and the earlier response seen in the lung metastases remained intact. This was a partial abscopal response [25] .
Preclinical studies:
In in vitro studies treatment with idronoxil and cisplatin inhibited nasopharyngeal carcinoma cells migration and cell proliferation (IC50 for idronoxil in 2D and 3D was 2µM; IC50 for cisplatin in 2D and 3D: was 0.6µM and 1.4µM, respectively). Dose-dependent induction of apoptosis in nasopharyngeal carcinoma cell lines was observed on treatment with idronoxil [early apoptotic cells (Annexin V+/PI- at 1µM); late apoptotic cells (Annexin V+/PI+ at 2µM), and necrotic cells (Annexin V-/PI+, at 4µM) were distinguished]. Idronoxil increased the migratory potential of PBMC towards tumor cells in both 2D and 3D spheroid cultures. Idronoxil facilitated the migration of CD8+ T cells toward tumour cells by 3.5-fold (p < 0.05) as well as promoted the expansion of proliferative CD8+ T cells (increased by ~2.8-fold) with degranulation activities (~1.3-fold and 3-fold increase in surface CD107a and intracellular granzyme B expression, respectively) in the cocultures, not observed on treatment with cisplatin [49] .
Results from preclinical studies demonstrates anti-inflammatory effect of idronoxil for the treatment of COVOD-2019 infections. Idronoxil inhibits the enzyme, TANK-binding kinase 1 (TBK1) that dampens the inflammatory response causing the progression of COVID-19 disease from mild-to-severe, but not compromising the body’s ability to fight the virus. TBK1 also controls production of interferon-beta which controls long lasting post infection symptoms [9] .
Therapeutic Trials
In the first-in-man phase Ib/IIa CEP-1 trial in patients (n=19) with solid tumours, idronoxil showed chemo-sensitising effect and restored carboplatin sensitivity who had stopped responding to chemotherapy, including carboplatin. Idronoxil, in combination with low-dose carboplatin suppressed tumour progression for six months in 50% patients. Post completion of 3 cycle of combination treatment, 10 of 14 evaluable patients showed stable disease (SD) and three patients showed progressive disease (PD). Of 8 patients who completed further 3 cycle of treatment (6 cycle total), 5 patients showed stable disease (SD) and one patient displayed partial response (PR) with almost 100% reduction in tumour size at the end of study. Patients received idronoxil as a monotherapy for the first month and then in combination with two dosages of carboplatin (3 cycles of carboplatin followed by 3 cycles of carboplatin at 50% and 75%, respectively of a standard dose) over six months, with total seven months of treatment [30] [29] [28] [27] .
Solid tumours
Phase I/II
Preliminary data from the phase I/II IONIC trial showed promising tumour responses from the idronoxil nivolumab combination therapy in patients with advanced cancer. Early signals of tumour response based on RECIST 1.1 criteria included stable disease in 2 patients (stable disease (SD) at 8 weeks and at 16 weeks); partial response (PR) in 1 patient at 16 weeks; complete response (CR) in 2 patients, both with ongoing complete response (CR) at 24 weeks. A significant increase in polyfunctionality in both effector CD4+ and CD8+ve T cells compared to baseline in responder patients was observed utilising a 32 multiplexed immune cytokine assay. The open label, non-randomised trial enrolled 11 patients [55] [54]
In updated results from the phaseIb DARRT-1 trial, approximately 66% men responded positively to idronoxil in combination with low-dose (20Gy) palliative radiotherapy to a single lesion, changed the course of the disease to a considerable degree in at least 66% of the men, with a halt to disease progression and high levels of pain relief lasting for the six months of observation. The study demonstrated 27% incidence of abscopal response (involves radiation directed at a single tumor which triggers resulting shrinkage of tumors well outside of the field of radiation) in soft tissue lesions using a combination of idronoxil and low-dose radiotherapy. Across all three idronoxi dosages (400, 800, 1200 mg); 1/15 patient had a partial response, 9/15 had stable disease and 5/15 had progressive disease, giving an overall tumour response rate of 66%, 5/16 patients (31%) had a PSA Response (>50% fall from baseline), with PSA reductions ranging from 61-98%, 10/16 patients (62%) had a Pain Response (>30% fall from baseline), with falls ranging from 43-100% (pain-free) [40] . Results from the DARRT-1 study demonstrated that no patients exhibited an abscopal response at 12-weeks in the 400mg cohort, while in the 800mg cohort, one patient had a partial abscopal response at 12-weeks. The first patient in the 1200mg cohort, reached the 6-week point and showed a partial abscopal response with a halving of the PSA count which was suggestive of a significant decrease in tumour load [36] . Highly durable disease control was demonstrated by progresion free survival of 57% (8/14) patients at 6 months. PSA response was achieved by 36% of patients at any point during follow up. Seven patients showed reduced pain levels at 3 months and pain resources were maintained in 5/7 patients at 6 months with two of these being pain-free [39] [42] [33] .
Data from phase I/II trial of idronoxil in combination with lutetium-177 PSMA (177Lu-PSMA) demonstrated a median overall survival (mOS) of 19.7 months in comparison to all other mOS results for existing prostate cancer treatments. Earlier data showed a prostate-specific antigen (PSA) response in 84% of patients with more than 50% in 62.5% of the patients. Median PSA progression free survival (PFS) is 6.1 months of men with increased baseline pain scores ≥3 (24/32). Significant reduction in pain indicators was observed in 50% (12/24) of the patients [21] . Earlier results from the trial, demonstrated a median overall survival of 17.1 months. The combination treatment almost doubled the PSA (Prostate-Specific Antigen)response (69% with idronoxil vs 36% with 177Lu-PSMA alone). Progression-free survival was quadrupled through the addition of idronoxil (8.4 months vs 2.0 months with 177Lu-PSMA alone). The median overall survival in a comparable patient population (exhausted all standard treatment options; progressive disease) receiving standard chemotherapy was only 4.5 months. The treatment duration was tripled to 69% from 21% with 177Lu-PSMA alone [20] . In interim data from the trial, idronoxil in combination with lutetium-177 PSMA 617 showed 69% higher PSA response rate (defined as a > 50% overall reduction in PSA) than with lutetium-177 PSMA 617 alone in 16 patients with mCRPC. PSA response rate in patients received 400mg and 800 dose was 62.5% and 75%, respectively. The PSA response rate was in favor with combination therapy than lutetium-177 PSMA 617 alone [22] [19] [17] [12] .
In a phase I NOXCOVID trial for the treatment of COVID-2019 infections, idronoxil showed anti-inflammatory response in COVID-19 patients. Earlier results from the trial demonstrated that, idronoxil provides protection against cytokine storm associated with worsening of COVID-2019 infections [8] [6] [4] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 01 Apr 2023 | Trial Update | Noxopharm plans part 2 of DARRT-2 phase II trial for solid tumours in late Q1 / early Q2 2023 [32] | 25 Jan 2023 |
| 01 Jan 2022 | Regulatory Status | Noxopharm intends to gain marketing approval for NOX 66 in 2022 [36] | 16 Aug 2018 |
| 17 Aug 2021 | Trial Update | Noxopharm plans a phase Ib/IIa trial for Prostate cancer and Solid tumours (Metastatic disease) in August 2021 (Rectal, Suppository) (NCT04957290) | 16 Jul 2021 |
| 31 Mar 2021 | Trial Update | Noxopharm in a collaboration with Bristol Myers Squibb plans a pilot IONIC-1 trial in Cancer (Combination therapy) early in 2021 [61] | 21 Nov 2020 |
| 31 Jan 2021 | Trial Update | Noxopharm plans to initiate the phase II DARRT-2 trial in early 2020 (700294344) [53] | 18 Nov 2021 |
| 30 Sep 2020 | Trial Update | Noxopharm plans the phase I NOXCOVID trial for COVID-2019 infections (Rectal) in September 2020 (NCT04555213) | 28 Sep 2020 |
| 31 Dec 2019 | Trial Update | Noxopharm plans the phase Ib CEP-2 trial for Sarcoma (Combination therapy) in the US in fourth quarter of 2019 (700306452) [62] | 07 Feb 2022 |
| 30 Sep 2019 | Trial Update | Noxopharm plans to initiate registrational adaptive phase II/III study in Prostate cancer for NOX 66 in third quarter of 2019 [63] | 10 Jan 2020 |
| 30 Jun 2019 | Trial Update | Noxopharm plans the phase II DAART-2 trial for Lung cancer in second quarter of 2019 [63] | 09 Dec 2019 |
| 30 Jun 2019 | Trial Update | Noxopharm plans the phase II DAART-3 trial for Sarcoma/rare cancer in second quarter of 2019 [63] | 09 Dec 2019 |
| 30 Mar 2019 | Trial Update | Noxopharm plans an IND-enabling phase 0 trial in healthy volunteers in first quarter of 2019 [63] | 26 Oct 2018 |
| 30 Apr 2017 | Trial Update | Royal North Shore Hospital plans a phase I trial for Prostate cancer (Metastatic disease, Second-line therapy or greater) in Australia (Suppository) (NCT03041285) | 16 Mar 2018 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 28 Oct 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in COVID-2019-infections in Moldova (Rectal, Suppository) Updated 28 Oct 2023 |
| 28 Aug 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Prostate-cancer(Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Georgia (Rectal, Suppository) Updated 28 Aug 2023 |
| 28 Aug 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Prostate-cancer(Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in New Zealand (Rectal, Suppository) Updated 28 Aug 2023 |
| 28 Aug 2023 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Diffuse intrinsic pontine glioma in Australia Updated 28 Aug 2023 |
| 12 Jun 2023 | Trial Update | Noxopharm terminates a phase I trial in Soft tissue sarcoma (Combination therapy) in USA (Rectal) due to slow recruitment (NCT05100628) Updated 28 Jun 2023 |
| 07 Jun 2023 | Trial Update | Noxopharm terminates a phase I/II trial in Prostate cancer (Second-line therapy or greater, Metastatic disease, Late-stage disease) in USA and Hungary (Rectal) due to slow recruitment (NCT04957290) Updated 23 Jun 2023 |
| 02 Jun 2023 | Scientific Update | Adverse events and efficacy data from a phase I/II IONIC trial in Solid tumours presented at the 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) [55] Updated 06 Jul 2023 |
| 24 Apr 2023 | Trial Update | Noxopharm discontinues the phase I CEP-2 clinical trials in Soft tissue sarcoma in USA (NCT05100628) Updated 03 May 2023 |
| 24 Apr 2023 | Trial Update | Noxopharm discontinues the phase-II DARRT-2 clinical trials in Solid tumours in USA Updated 03 May 2023 |
| 27 Jan 2023 | Patent Information | Noxopharm has patent protection for isoflavonoid composition with improved pharmacokinetics in USA [47] Updated 14 Feb 2023 |
| 17 Jan 2023 | Trial Update | Noxopharm plans part 2 of DARRT-2 phase II trial for solid tumours in late Q1 / early Q2 2023 [32] Updated 25 Jan 2023 |
| 29 Mar 2022 | Regulatory Status | Idronoxil - Kazia Therapeutics/Noxopharm receives Orphan Drug status for Soft tissue sarcoma in USA [45] Updated 31 Mar 2022 |
| 17 Jan 2022 | Phase Change - I | Phase-I clinical trials in Soft tissue sarcoma (Combination therapy) in USA (Rectal) (NCT05100628) Updated 07 Feb 2022 |
| 10 Nov 2021 | Patent Information | Noxopharm intends to file patent allowance for idronoxil combination with radiotherapy in USA before November 2021 [52] Updated 18 Nov 2021 |
| 10 Nov 2021 | Phase Change - II | Phase-II clinical trials in Solid tumours in USA (unspecified route) in November 2021 [52] Updated 18 Nov 2021 |
| 31 Oct 2021 | Phase Change - I | Phase-I clinical trials in Solid tumours (Combination therapy, Second-line therapy or greater) in Australia (Rectal) [47] (Noxopharm website:- https://www.noxopharm.com/our-programs/clinical/ionic) Updated 14 Feb 2023 |
| 29 Oct 2021 | Biomarker Update | Biomarkers information updated Updated 31 Oct 2021 |
| 11 Oct 2021 | Phase Change - I/II | Phase-I/II clinical trials in Prostate cancer (Second-line therapy or greater, Metastatic disease, Late-stage disease) in USA (Rectal) (NCT04957290) Updated 19 Oct 2021 |
| 11 Oct 2021 | Phase Change - I/II | Phase-I/II clinical trials in Solid tumours (Metastatic disease, Second-line therapy or greater, Late-stage disease) in USA (Rectal) (NCT04957290) Updated 19 Oct 2021 |
| 02 Sep 2021 | Trial Update | Noxopharm completes a phase I trial in COVID-2019 infections in Moldova (Rectal) (NCT04555213) Updated 02 Sep 2021 |
| 27 Aug 2021 | Scientific Update | Noxopharm pharmacodynamics data from a preclinical trial in COVID-2019 infection released by Noxopharm [9] Updated 30 Aug 2021 |
| 25 Aug 2021 | Scientific Update | Interim efficacy and adverse events data from a phase I Noxopharm trial in COVID-2019 infections released by Noxopharm [8] Updated 27 Aug 2021 |
| 19 Aug 2021 | Active Status Review | Idronoxil is in phase I trial in Prostate cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Georgia and New Zealand (Rectal) (NCT03307629) Updated 19 Aug 2021 |
| 12 Aug 2021 | Trial Update | Noxopharm completes the phase I/II LuPin trial in Prostate cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Australia (Rectal) (ACTRN12618001073291) [11] Updated 19 Aug 2021 |
| 12 Jul 2021 | Trial Update | Noxopharm plans a phase Ib/IIa trial for Prostate cancer and Solid tumours (Metastatic disease) in August 2021 (Rectal, Suppository) (NCT04957290) Updated 16 Jul 2021 |
| 27 Apr 2021 | Scientific Update | Interim efficacy data from a phase I trial in COVID-2019 infections released by Noxopharm [6] Updated 29 Apr 2021 |
| 14 Apr 2021 | Phase Change | Early research in Influenza virus infections in Australia (unspecified route) [60] Updated 06 May 2021 |
| 14 Apr 2021 | Patent Information | Noxopharm files international patent application for idronoxil for treatment of septic shock [60] Updated 16 Apr 2021 |
| 18 Mar 2021 | Trial Update | Noxopharm initiates enrolment in a part 2 of phase I trial for COVID-2019 infections in Moldova (NCT04555213) [5] Updated 22 Mar 2021 |
| 11 Feb 2021 | Scientific Update | Efficacy data from a phase I/II trial in prostate cancer presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-2021) [22] Updated 15 Feb 2021 |
| 28 Dec 2020 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Prostate-cancer(Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Georgia (Rectal, Suppository) Updated 28 Dec 2020 |
| 28 Dec 2020 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Prostate-cancer(Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in New Zealand (Rectal, Suppository) Updated 28 Dec 2020 |
| 03 Dec 2020 | Trial Update | Noxopharm plans to initiate the phase II DARRT-2 trial in early 2020 [53] Updated 18 Nov 2021 |
| 12 Nov 2020 | Trial Update | Noxopharm in a collaboration with Bristol Myers Squibb plans a pilot IONIC-1 trial in Cancer (Combination therapy) early in 2021 [61] Updated 21 Nov 2020 |
| 30 Sep 2020 | Phase Change - I | Phase-I clinical trials in COVID-2019 infections in Moldova (Rectal) (NCT04555213) Updated 22 Mar 2021 |
| 18 Sep 2020 | Trial Update | Noxopharm plans the phase I NOXCOVID trial for COVID-2019 infections (Rectal) in September 2020 (NCT04555213) Updated 28 Sep 2020 |
| 15 Sep 2020 | Trial Update | Noxopharm completes a phase I DARRT-1 trial in Prostate cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Australia, Georgia and New Zealand (Rectal) (NCT03307629) Updated 29 Sep 2020 |
| 29 May 2020 | Scientific Update | Safety and efficacy data from a phase I/II trial in Prostate cancer presented at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020) [21] Updated 26 Jun 2020 |
| 29 May 2020 | Scientific Update | Pharmacodynamics data from a preclinical trial in Nasopharyngeal cancer presented at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020) [49] Updated 13 Jun 2020 |
| 20 May 2020 | Trial Update | Noxopharm completes a phase I trial in healthy volunteers in Australia (Rectal) (ACTRN12620000002987) Updated 10 Dec 2020 |
| 07 May 2020 | Scientific Update | Efficacy data from a phase Ib trial in Prostate cancer released by Noxopharm [39] Updated 09 May 2020 |
| 07 Apr 2020 | Phase Change - Preclinical | Preclinical trials in Nasopharyngeal cancer in Australia (unspecified route) [50] Updated 09 Jun 2020 |
| 02 Apr 2020 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections in Australia (Rectal) [44] Updated 08 Apr 2020 |
| 02 Apr 2020 | Trial Update | Noxopharm plans clinical trial for COVID-2019 infections (associated with acute respiratory distress syndrome (ARDS) and multi-organ failure) [44] Updated 08 Apr 2020 |
| 26 Feb 2020 | Regulatory Status | Noxopharm intends to file an IND application with the US FDA in USA for late-stage Prostate cancer [48] Updated 27 Feb 2020 |
| 26 Feb 2020 | Regulatory Status | US FDA approves IND application for Idronoxil in combination with doxorubicin in Soft tissue sarcomas [48] Updated 27 Feb 2020 |
| 26 Feb 2020 | Trial Update | Noxopharm plans a Clinical trial for Soft tissue sarcoma (Combination therapy) in USA [48] Updated 27 Feb 2020 |
| 26 Feb 2020 | Trial Update | Noxopharm plans a Clinical trial for Prostate cancer (Late-stage disease) in USA [48] Updated 27 Feb 2020 |
| 18 Feb 2020 | Trial Update | Noxopharm and GenesisCare plans to provide idronoxil and 177 Lutetium PSMA 617 under a compassionate use programme for Prostate cancer in Australia [23] Updated 26 Feb 2020 |
| 16 Feb 2020 | Scientific Update | Updtaed efficacy data from the phase I/II LuPIN trial in Prostate cancer released by Noxopharm [19] Updated 19 Feb 2020 |
| 03 Dec 2019 | Regulatory Status | Noxopharm announces intention to submit IND for DARRT-2 studies to the US FDA, EMA and TGA [40] Updated 09 Dec 2019 |
| 03 Dec 2019 | Regulatory Status | Noxopharm announces intention to submit IND for DARRT-3 studies to the US FDA, EMA and TGA [40] Updated 09 Dec 2019 |
| 03 Dec 2019 | Scientific Update | Efficacy and safety data from a phase Ib DARRT-1 trial in Prostate cancer released by Noxopharm [40] Updated 09 Dec 2019 |
| 05 Nov 2019 | Trial Update | Noxopharm initiates enrolment in a phase I trial in healthy volunteers in Australia (ACTRN12620000002987) Updated 10 Jan 2020 |
| 30 Sep 2019 | Scientific Update | Efficacy and safety data from the phase I/II LuPIN trial in Prostate cancer released by Noxopharm [20] Updated 09 Oct 2019 |
| 30 May 2019 | Trial Update | Noxopharm completes enrolment in a phase I DARRT-1 trial in Prostate cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Australia, Georgia and New Zealand (Rectal) [25] (NCT03307629) Updated 03 Jun 2019 |
| 20 May 2019 | Scientific Update | Interim efficacy and adverse events data from the phase Ib LuPIN trial in Prostate cancer released by Noxopharm [17] Updated 23 May 2019 |
| 03 May 2019 | Scientific Update | Update interim efficacy data from the phase Ib (DARRT-1) trial in Prostate cancer released by Noxopharm [42] Updated 09 May 2019 |
| 10 Apr 2019 | Trial Update | Noxopharm plans the phase Ib CEP-2 trial for Sarcoma (Combination therapy) in the US in fourth quarter of 2019 [62] Updated 07 Feb 2022 |
| 02 Jan 2019 | Trial Update | Noxopharm completes phase I/II clinical trials in Solid tumours (Late-stage disease, Monotherapy, Combination therapy, Refractory metastatic disease, Second-line therapy or greater) in Georgia in January 2019 (NCT02941523) Updated 10 Jun 2021 |
| 27 Dec 2018 | Other | Chemical structure information added Updated 27 Dec 2018 |
| 29 Nov 2018 | Scientific Update | Interim efficacy and adverse events data from a phase Ib/II trial in Solid tumours released by Noxopharm [30] Updated 03 Dec 2018 |
| 22 Oct 2018 | Trial Update | Noxopharm plans to initiate registrational adaptive phase II/III study in Prostate cancer for NOX 66 in third quarter of 2019 [63] Updated 10 Jan 2020 |
| 22 Oct 2018 | Trial Update | Noxopharm plans the phase II DAART-2 trial for Lung cancer in second quarter of 2019 [63] Updated 09 Dec 2019 |
| 22 Oct 2018 | Trial Update | Noxopharm plans the phase II DAART-3 trial for Sarcoma/rare cancer in second quarter of 2019 [63] Updated 09 Dec 2019 |
| 22 Oct 2018 | Trial Update | Noxopharm plans an IND-enabling phase 0 trial in healthy volunteers in first quarter of 2019 [63] Updated 26 Oct 2018 |
| 08 Aug 2018 | Regulatory Status | Noxopharm intends to gain marketing approval for NOX 66 in 2022 [36] Updated 16 Aug 2018 |
| 08 Aug 2018 | Scientific Update | Efficacy and adverse events data from the phase Ib (DARRT) trial in Prostate cancer released by Noxopharm [36] Updated 16 Aug 2018 |
| 10 Jul 2018 | Phase Change - Preclinical | Preclinical trials in Diffuse intrinsic pontine glioma in Australia (unspecified route) Updated 13 Jul 2018 |
| 09 Jul 2018 | Scientific Update | Interim adverse events data from the phase Ib DARRT-1 trial in Prostate cancer released by Noxopharm [35] Updated 13 Jul 2018 |
| 01 Jun 2018 | Scientific Update | Interim adverse events and efficacy data from the phase Ib/IIa trial for Solid tumours presented at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018) [29] Updated 02 Jul 2018 |
| 12 Apr 2018 | Trial Update | Noxopharm initiates enrolment in a phase I LuPin trial in Prostate cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Australia (Rectal) (ACTRN12618001073291) [13] Updated 10 May 2018 |
| 21 Mar 2018 | Scientific Update | Pharmacodynamics data from clinical studies of idronoxil novel formulation released by Noxopharm [25] Updated 26 Mar 2018 |
| 21 Mar 2018 | Trial Update | Noxopharm plans the DARRT-2 phase II trial for Solid tumours [25] Updated 26 Mar 2018 |
| 06 Mar 2018 | Scientific Update | Efficacy and adverse events data from the phase Ib CEP-1 trial in Solid tumours presented at the European Society for Medical Oncology Congress - 2018 (ESMO-2018). [28] Updated 16 Mar 2018 |
| 22 Jan 2018 | Patent Information | Kazia Therapeutics has intellectual property protection for idronoxil novel formulation [2] Updated 01 Feb 2018 |
| 27 Dec 2017 | Licensing Status | Kazia Therapeutics acquires idronoxil novel formulation from Noxopharm [3] Updated 01 Feb 2018 |
| 01 Nov 2017 | Trial Update | Noxopharm initiates enrolment in a phase I DARRT-1 trial in Prostate cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Australia (Rectal) [25] (NCT03307629) Updated 09 Apr 2018 |
| 01 Nov 2017 | Phase Change - I | Phase-I clinical trials in Prostate cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Georgia and New Zealand (Rectal) [25] (NCT03307629) Updated 26 Mar 2018 |
| 31 Aug 2017 | Phase Change - I | Phase-I clinical trials in Prostate cancer (Combination therapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Australia (Rectal) (NCT03041285) Updated 16 Mar 2018 |
| 03 Mar 2017 | Phase Change - I/II | Phase-I/II clinical trials in Solid tumours (Monotherapy, Late-stage disease, Refractory metastatic disease, Second-line therapy or greater) in Georgia (NCT02941523) Updated 06 Apr 2017 |
| 03 Mar 2017 | Phase Change - I/II | Phase-I/II clinical trials in Solid tumours (Late-stage disease, Combination therapy, Refractory metastatic disease, Second-line therapy or greater) in Georgia (NCT02941523) Updated 03 Apr 2017 |
| 31 Jan 2017 | Trial Update | Royal North Shore Hospital plans a phase I trial for Prostate cancer (Metastatic disease, Second-line therapy or greater) in Australia (Suppository) (NCT03041285) Updated 16 Mar 2018 |
| 26 Jun 2016 | Phase Change - Preclinical | Preclinical trials in Cancer in Australia [26] Updated 03 Apr 2017 |
| 26 Jun 2016 | Trial Update | Noxopharm plans a phase I/IIa trial for Cancer, including solid tumours (Monotherapy, Combination therapy, Metastatic disease, Second-line therapy or greater) (NCT02941523) [26] Updated 29 Mar 2017 |
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