Soft tissue sarcomas
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  .
In November 2019, Noxopharm initiated a phase I trial to evaluate the safety and absorption of a new formulation of idronoxil in healthy volunteers (NOX66-006; 378739; 2019-09-824; ACTRN12620000002987). The open label trial intends to enrol approximately 24 volunteers in Australia  .
In April 2018, Noxopharm commenced an investigator-initiated, 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 is enrolling approximately 52 males in Australia    . 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  . 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  . In May 2019, interim efficacy and safety data from the trial were released by Noxopharm  . 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    .
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   . 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  .
In March 2017, Noxopharm initiated a first-in-man phase Ib/IIa 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 is enrolling approximately 36 adult and elderly patients, in the US. The phase IIa part of study will be initiated based on results from the phase Ia/Ib part of the trial   . 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)  . In June 2018, the company presented interim results at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO-2018)  . In November 2018, Noxopharm released final data from the phase Ib portion of the trial  .
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    .
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. In November 2017, Noxopharm initiated a proof-of-concept phase Ib DARRT-1 (Direct and Abscopal Response to Radiotherapy- 1) study to investigate 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). The open label, non-randomised, pilot, dose confirmation study is enrolling approximately 26 patients in Australia, New Zealand and Georgia  . The study is designed to treat patients in escalating dose level cohorts of NOX 66 (400 mg, 800 mg and 1200 mg in cohort 1, 2 and 3) of four patients in each cohort, total 12 patients and an expansion cohort of 12 patients (cohort 4), to determine the optimal dose for future radiation therapy combination studies   . Idronoxil is administered daily for the duration of the radiotherapy treatment plus 7 days  . In April 2018, the company treated the first cohort of four patients  . In July 2018, the company released interim safety data   . In December 2018, Noxopharm announced that the DARRT-1 study has been approved to move to its final stage, with enrolment of 12 patients at a dosage of 1200mg idronoxil  . Noxopharm completed enrolment in the trial, in May 2019. Subsequently topline results were released. Safety and efficacy results were presented by the company in December 2019     .
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  .
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)  .
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  .
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  .
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  .
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   .