PERTH, Australia – Following positive results across three different oncology clinical trial programs with its lead candidate, Veyonda, Sydney-based Noxopharm Pty Ltd. has secured a AU$26 million (US$18 million) funding facility from U.S. investors leading up to a proposed Nasdaq listing.

The funding facility includes initial funding of AU$4 million and an equity placement component up to AU$22 million in ordinary shares over 12 months.

To date, Noxopharm has released interim clinical data from both its DARRT-1 and LuPIN studies, both of which paired different radiotherapy regimens with Veyonda (formerly OX-66) showing encouraging results that the compound showed anticancer responses in men with metastatic castration-resistant prostate cancer. Another combination study with chemotherapy also showed positive results across a number of solid tumors.

The funds will allow the company to expand and accelerate its Veyonda clinical program into immuno-oncology clinical trials.

"What we've learned about this drug makes us believe it's got a much brighter future than we ever imagined," Noxopharm founder and Executive Chairman Graham Kelly told BioWorld.

"And while the value of Veyonda is growing, so is the cost of its development, and that means laying the groundwork for a future strongly linked to the U.S. capital markets," he said.

He stressed that the Veyonda actions as a radio-enhancer and immuno-oncology drug align with "emerging frontiers in cancer therapy," including the use of radiotherapy to induce abscopal responses and the use of intravenous radiopharmaceuticals to recruit the body's innate immune system to fight cancer.

He said that an abscopal response and STING (stimulator of interferon genes) effect seen with Veyonda could be a game-changer for the company. "Most drugs start in the clinic with a pretty clear indication of how they work, and we started with a drug that had multiple actions that could have been used in a number of different ways, so we deliberately ran a three-horse race looking at using it to make chemotherapy drugs more effective, and to use it with I.V. radiotherapy as well as with an external beam radiotherapy machine."

Abscopal response seen in radiotherapy

The Direct and Abscopal Response to Radiotherapy (DARRT) study is investigating Veyonda in combination with low-dose external beam radiotherapy in men with late-stage, metastatic, castration-resistant prostate cancer (mCRPC) with 20 or more tumors.

The regimen involves a short course of Veyonda for 15 days and then a low dose of external beam radiation applied to a single tumor.

About 50% of patients experienced a significant decrease in pain. Kelly said that PSA levels are dropping, and the trial is showing an effect on the tumors in the skeleton even though a different tumor was radiated in the trial.

Interim results reported in May showed that 57% of patients were progression-free at six months. In addition, 36% of patients achieved more than a 50% reduction in PSA levels, and seven of 14 patients exhibited reduced pain levels. Two patients were pain-free at six months. Top-line data will be announced in the fourth quarter.

"Lack of disease progression and a significant reduction in pain levels point to anticancer responses in lesions in the skeleton where no radiation was delivered. We believe this is associated with an off-target response known as an abscopal response and likely is associated with the immuno-oncology effects of Veyonda," Kelly said.

"Because we were seeing this abscopal response, we started working on this in animals at the Olivia Newton John Cancer Research Center, and there we saw a STING response as a potential mechanism," he added.

Kelly explained that the STING effect has come under the radar due to the failure of checkpoint inhibitors to live up to the earlier responses seen in melanoma and lung cancer.

"It turned out that in melanoma the response rate for checkpoint inhibitors was only about 15 percent and lung cancer was about the same. And, in tumors like breast, colorectal and ovarian, the response rate is much lower, because many of these tumors were cold tumors and didn't respond to checkpoint inhibitors," he said.

The STING effect triggers an immune response and turns those cold tumors into hot tumors, because the interferons drag immune cells into the tumor.

"We understand that idronoxil, the active ingredient in Veyonda, is a STING enhancer, and we have unequivocal evidence that this is the case. That abscopal response in our prostate cancer patients is a STING effect."

To test that theory, the company is adding a fourth arm to study Veyonda in combination with a checkpoint inhibitor.

"For example, in lung cancer, we'll re-treat patients who failed with checkpoint inhibitors because their tumors were cold to see if we can turn them into hot tumors and get a much better response.

"That may be the ultimate home for idronoxil. Where you start and where you finish are often very different," he said.

"The DARRT trial has to be a STING effect. It could also be present in the LuPin trial. We expect to see a more dramatic effect in the checkpoint inhibitor program." Kelly said the lung cancer trial is expected to start up in about six months.

LuPin interim results

Interim results from the LuPIN study showed an overall response rate of 69% in heavily pre-treated men with progressive late-stage prostate cancer. The 56-patient phase Ib/IIa study is evaluating the safety and efficacy of Veyonda combined with intravenous radiopharmaceutical 177Lu-PSMA-617 in men with progressive metastatic castration-resistant prostate cancer following chemotherapy.

Data from the first 16 patients show a 50% reduction in PSA levels compared to baseline. Overall survival was 100% at three months, 93% at six months and 81% at 12 months.

In addition, final results of the phase Ib trial evaluating Veyonda in combination with low-dose carboplatin in late-stage metastatic solid cancers confirmed the safety of Veyonda both as a monotherapy and in combination with chemotherapy.

The CEP-1 study recruited 19 subjects with late-stage metastatic solid cancers (breast, ovarian, lung, prostate) who had stopped responding to chemotherapy, and for whom no remaining standard treatment options were available. Subjects were administered Veyonda as a monotherapy for the first month and then in combination with two dosages of carboplatin.

The combination of Veyonda and low-dose carboplatin stopped disease progression for at least six months in solid tumors (breast, ovarian, lung, prostate) in nearly 50% of patients.

"We were able to wind back the carboplatin dose significantly to about half the normal dose, so we were able to offer something to that group of patients," Kelly said, noting that the combination therapy could present a good option for those cancer patients considered too unwell to undergo chemotherapy and or unlikely to respond to chemotherapy.

The study is now being expanded to investigate Veyonda in combination with doxorubicin in sarcomas, which is being run in parallel with the two radiotherapy programs. That study is expected to start in the U.S. later this year.

Kelly said that Noxopharm expects the U.S. Nasdaq listing to take place in the next few months. The company completed its IPO on Australia's Securities Exchange (ASX:NOX) in July 2016 and raised AU$6 million. (See BioWorld, Nov. 2, 2016.)

The funding facility was granted by New York-based investors Lind Global Macro Fund LP, managed by The Lind Partners, and LLC and CST Investment Funds.

Noxopharm's market cap is roughly AU$55 million; its shares on the ASX closed Friday at AU46 cents per share.

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