Fascinating Interview

Australian Biotech’s Mission to Commercialize the Drug that Saved Its Founder’s Life

Apr 23, 2020 | Blog, Immunotherapy, Investor Watch, Isoflavones, News, Noxopharm, Oncology, Prostate Cancer, Sarcoma

TrialSite News recently had the honor of interviewing Graham Kelly, a brilliant scientist, researcher, and Executive Chairman and CEO of Australia’s Noxopharm. Dr. Kelly established expertise in both organ recovery for transplantation and liver transplant surgery while a senior researcher at the University of Sydney. This led to an interest in the link between diet and incidences of certain cancers. Fascinated by dietary isoflavones and their role in human health, the young researcher theorized these substances were metabolized by the body into novel chemicals with vital hormone-like functions consequently making important contributions to human health. He left academia with big aspirations for converting his theory into life-extending and saving-drugs and founded Novogen in 1992. Thereafter, the Dr. Kelly navigated the world of big biotech business and finance, helping to bring his company public on the ASX in 1994 and the Nasdaq in 1999. Valued at over one-billion dollars, Navogen struggled, not because of its investigational drug, but rather because of how it was dosed and delivered. During a near-death battle with prostate cancer himself, he was the first to consume the drug Veyonda combined with radiotherapy. This beat back his cancer, keeping him around to strive to help others. Now he is on a mission to finance the next wave of clinical trials in the journey to commercialize Veyonda.

One can’t help but be impressed with Dr. Kelly’s deep scientific, medical and clinical expertise; his business and financial acumen; and his humanistic and pre-eminent wisdom. The Australian has seen much in his life, including staring at his own looming end due to advanced prostate cancer, and he gently and affably commands attention from anyone in the room. What follows is a brief summary of our conversation, interwoven with a summary of the investigational product and the venture.

What is Noxopharm?

Although this venture was formed in 2015 via a reverse merger, it is just the latest manifestation of Dr. Kelly’s long and illustrious career focused on bringing into reality what he knew to be a profound clinical breakthrough. The genesis of Veyonda goes way back in his interesting, diverse and successful career; but the commercial materialization of the drug comes from a profound and burning desire to finish something he knows can help potentially tens of thousands of patients struggling with late-stage cancer.

Few in his shoes have his credibility, authority, and real-time empathy with the patient. He too faced a dire, late-stage, metastatic prostate cancer prognosis. The very drug that he is advancing down the clinical pipeline saved his own life. Kelly faced the specter of late-stage prostate cancer with advanced metastatic disease. After treatments based on the combination of Veyonda and radiotherapy, the cancer went into complete remission thanks to what oncologists call an abscopal response. This is when exposure of single tumors to low-dose radiotherapy leads to complete remission, and five years later, he remains cancer free.

Was the first time just luck?

Well it could have been, if Dr. Kelly would have just enjoyed more time with his beloved wife, family and friends. But a spirited, relentless soul such as Kelly doesn’t align well with retirement on a nice Australian golf course. Hence, he was actively probing for opportunity to prove his case. And as it turns out, he received a request to take the investigational drug Veyonda on a compassionate use basis. The request came from a woman with an advanced metastatic sarcoma that was considered “untreatable.” The investigational treatment was approved, and lo and beyond, the combination of Veyonda and low-dose radiotherapy directed at the primary lesion in the abdomen produced shrinkage in multiple tumors, ultimately leading to what was considered a “partial abscopal response.” One time—maybe luck; two times in a row—a trend.

But what was the drug that first extended Kelly’s life and now keeps him up at night, moving a company forward in the quest for commercialization?

The NCI’s Definition of Veyonda (NOX66)

As described by the National Cancer Institute (NCI), this proprietary, suppository-based formulation of idronoxil, a synthetic flavonoid derivative discovered by Dr. Kelly, is surrounded by a proprietary lipid that protects idronoxil from Phase 2 degradation, with potential chemo-and radio-sensitizing activities.

Upon administration, idronoxil blocks the activity of ecto-NOV disulfide-thiol exchanger 2 (ENOX2; tNOC), a tumor-specific external NADH oxidase that maintains the transmembrane electron potential across the plasma membrane and is overexpressed in certain cancer cell types and absent in normal, healthy cells.

This loss directly inhibits certain pro-survival signal transduction pathways, such as the PARP1/P13 kinase/Akt signaling pathway. Hence, the inhibition of these pathways stops resistance to standard chemo-and-radio-therapy and thereby makes tumor cells more susceptible to the anti-tumor activity of conventional chemotherapeutic agents and radiotherapy. This formulation prevents detoxification of idroxoxil to an inactive form by bypassing phase 2 metabolism and hence increases idronoxil’s bioavailability as compared to the drug alone.

Was he able to raise capital to get a clinical trial going?

Yes. Believing that there are no coincidences, Kelly, who had already bet his life taking the experimental drug and was now ready to bet everything else he had to back the company, raised public funds and post-IPO debt to launch a clinical trial program. He successfully raised funds, starting with a $7.5 million public listing, to commence a first study called DARRT-1 in addition to developing a clinical trials pipeline.

Why was there investor interest?

First and foremost, those that were able to hear Dr. Kelly discuss his compelling story had to at least consider the opportunity. How many serious academic-turned-scientist-turned-biotech executives have literally taken their own medicine? Moreover, it worked!

The company positions Veyonda into the late-stage oncology market—end-stage cancer patients who don’t have good treatment prospects at all. Once in palliative care, in this close-to-the-end state, there are few treatments that will do any good. But what if there was an approach that wasn’t disruptive and didn’t cause any further discomfort, was economical, and synced well with the standard approach for patients at this stage? What if, by combining Veyonda and low-dose radiotherapy, which is already proven to be well tolerated and minimally intrusive (important factors for those facing the quality-of-life issues associated with advanced cancer), patients could realize therapeutic benefits and potential gain game-changing benefits, such as the type Dr. Kelly has benefited from?

Well, this could be considered a game-changing situation for anyone that wants a family member around longer. And there are many patients facing this situation. The company believes that this market represents a multi-billion-dollar opportunity with little competition.

Their immediate goal would be to target late-stage prostate cancer patients—estimated at 300,000 patient deaths per years; 33,000 in the U.S. in 2020. Of course, Kelly understands this market in a very personal way. He is here today thanks to this investigational drug. The company speculates that the U.S. market alone could be worth an estimated $1 billion plus once the markets understood this kind of approach was feasible.

The company articulates to investors that risks are mitigated as: 1) safety has been confirmed, 2) evidence exists of meaningful clinical efficacy in Phase I/II trials, via 3) multiple clinical programs including DARRT, LuPIN, CEP and IONIC. Moreover, as the company has developed a partnership with oncology provider GenesisCare, they believe commercialization is within reach.

The Phase I Study

The DARRT-1 study was launched as a Proof-of-Concept and dose confirmation study. The sponsor objective is to observe safety and tolerability of idronoxil (NOX66) in combination with radiotherapy (at palliative doses) in patients with metastatic castrate-resistant prostate cancer (CRPC) and to confirm dose in order to progress studies to Phase II and III. The study commenced Nov. 2017 with primary completion date by 2019.

What were the Results?

The company reported exciting results. Dr. Kelly reported, “This is exciting data that validates our confidence in the future of NOX66 DARRT treatment regimen. NOX66 DARRT has delivered a very meaningful anti-cancer effect in a high proportion of men, halting progression of their disease and providing an average 80% reduction in their pain levels, including some men becoming pain-free.”

In many cases, men, struggling with severe pain, poor quality of life and little hope saw improvements; Kelly noted, “A 66% response rate is a substantial response rate for such late-stage disease, putting NOX66 DARTT right at the top end of the response rates in late -stage cancer.”

What about the COVID-19 discussions?

TrialSite News actually reported on Dr. Kelly’s company recently. We discussed how cytokine-response syndrome (and associated cytokine storms) with an excessive and abnormal inflammatory response were believed to be a cause of many, if not most, COVID-19 deaths. If there was a way to reduce or even stop this phenomenon, could more lives be saved?

Well, that was the thinking of the Hudson Institute of Medical Research in Melbourne along with Noxoharm. Preclinical researchers at the Institute found that the active ingredient in Veyonda, idronoxil, actually acts as a potent inhibitor of IL-6 production. This has the potential to impact acute respiratory syndrome, reported Dr. Michael Gantier, head of the Nucleic Acids and Innate Immunity Laboratory. Dr Gantier continued, “However, unlike strategies of targeting IL-6 itself, our findings suggest that idronoxil blocks the process of IL-6 production along with that of other key mediators of organ failure.”

Thereafter, Noxopharm noted it would pursue a possible clinical trial to evaluate the use of idronoxil in patients considered to be at severe risk of developing COVID-19 associated respiratory distress syndrome (ARDS) and multi-organ failure.

TrialSite News asked Dr. Kelly whether he has any advice for up-and-coming researchers?

He has encouraged his scientists to take risks—he finds this incredibly important, that at some point the serious scientist will have to put his/her career on the line for an important advancement. He emphasized that in the past, whether in an academic, research or business environment, that we won’t come down on people for making mistakes. If there is one truism: “The current dogma isn’t working.” Why? Well, he declared, “Take a look around—look at all of the diseases we have found no cure for.” Hence for one to think “out -of-the-box” they must find some mission they truly align with—intellectually, professionally and scientifically—and “go for it.”

What is the one thing you are most proud of?

“Marrying my beautiful wife!”