A look at The Veyonda Story to now

Having recently celebrated our 5th anniversary is an appropriate time to look back on the Company’s beginnings and the path to the current.


The start

Some people said it was hardly a propitious start …  building a business around a drug that had failed a Phase 3 study. Nevertheless, I had seen the drug work in enough patients, including a personal experience, to be confident that the Phase 3 failure was due to operator error, not equipment failure. Idronoxil (IDX) very simply was too good a drug to walk away from.

Operator error meant going back to basics and dismissing all the old notions about IDX - how it worked, how best to administer it, and how best to use it. We needed to start from scratch.

Correcting operator error

In its pre-Noxopharm days, IDX came in both oral and intravenous forms, with the oral dosage form adopted eventually as being more convenient for both patient and doctor.

Noxopharm research in this area has gone on to prove two of the great truisms of science - biological systems are rarely as simple as you think and the answer is almost always the opposite of what you think.

IDX is no different to any other drug introduced into the body …. the body assumes that any foreign chemical is potentially harmful and takes whatever steps necessary to eliminate it just as quickly as it can. One of the main ways it does this is to chemically modify the drug, and this modification takes place mainly in the liver. This chemical modification ensures the drug is excreted by the kidneys as quickly as possible, but it also in many cases changes the potency of the drug, sometimes increasing it and other times decreasing it. IDX is in the category of drugs where its anti-cancer potency is decreased.
The text-books say that it doesn’t matter how a drug, any drug, gets into the body (mouth, intravenous injection, through the skin etc) because it eventually ends up passing through the liver where it is subject to this chemical modification, and that therefore how it gets into the body makes no difference.
Early operator error in the case of IDX came about because, despite what the text-books said, it emerged that the issue for IDX is not the fact that it reaches the liver, but how it reaches the liver. There may be other drugs similarly affected, but I am not aware of any, and understanding this exception to the rule is what led to the formation of Noxopharm and what gives the Company a unique technology platform.
Understanding this exception to the rule requires a bit of basic anatomy. Blood reaches the liver by two routes – via the portal vein (draining the stomach and intestines) and via the hepatic artery (from the general circulation). A drug given orally comes into the liver by the portal vein; a drug given anywhere else in the body comes in via the hepatic artery. I am not going to go into the details of this because it is the subject of ongoing patent applications, but it is critical to the way that IDX works.
Pre-NOX, before this difference was known, the initial IDX clinical trials involved intravenous dosing, with positive clinical signals. However, with the realization that IDX needed to be present in the body on a constant basis over periods of about 14 days, oral dosing looked far more practical for both doctor and patient, and that became the dosage form taken into the Phase 3 study. That meant delivering the IDX via the portal vein, and the result was that the drug struggled to work.
Rectal dosing (suppository) delivers IDX to the liver in the same way as an intravenous injection, via the hepatic artery. A suppository is simply a more practical and more convenient method of dosing compared to daily intravenous injections. 
That is the story of NOX-66 (Veyonda) and why we are confident that we can now fulfill the promise of IDX.
Fixing this early operator error has had an unexpected additional benefit, and that is that it has led to the development of the next generation of IDX, currently underway and part of the oncology pipeline – a first cousin of IDX offering greater potency and new proprietary intellectual property.


Determining the best way to use the drug

With operator error fixed, the next step was to work out how best to use IDX.

When NOX started, we inherited about 20 years of knowledge of how IDX worked. Over 50 scientific publications showing that IDX possessed the fairly standard anti-cancer actions of somewhere between stopping cancer cells from dividing and  killing them.

These anti-cancer actions are strong enough that IDX could be looked at as a stand-alone drug, but in the early-2000s, Yale University scientists involved in the drug’s development believed that a better way was to use it to make other chemotherapies work better, the so-called chemo-enhancing action. They showed in the lab that IDX was able to make many other commonly used chemotherapy drugs work hundreds and in some cases even thousands of times stronger when combined with IDX. That way you got the dual benefit of the anti-cancer effects of IDX on its own plus those of a super-charged second chemotherapy drug.

We knew from laboratory studies that IDX turned chemotherapy drugs like carboplatin into far more potent anti-cancer agents, and despite a combination of IDX and carboplatin failing to deliver the goods in a large Phase 3 study, I was confident that we had identified and fixed the problem, so that picking up from where the previous program had faltered seemed a logical plan.

Of course, in 2016, a chemo-enhancing effect was really all we knew about how IDX was working, so the clinical option was pretty much self-determining. Not that that was a problem, with chemotherapy remaining the main form of cancer therapy. With the chemotherapy market worth in the order of US$150 billion p.a., I didn’t need to be persuaded then or 5 years later to pursue chemo-enhancement as a clinical option. Anything that makes a US$150 billion market more effective, and hopefully safer (through reduced drug dosages), has to be a potential blockbuster opportunity. Hence our Chemo-Enhancing Program (CEP), one of our current 4-pillars strategy.

For our first study (CEP-1), we decided to push the boundaries a bit further and use the combination to enable lower, safer dosages of carboplatin to be used. This was a key part of our patent strategy which I am happy to say is starting to bear fruit with recent grants by the Australian, European and Japanese patent offices.

The CEP-1 study combined IDX with carboplatin dosages between roughly half to two-thirds of standard levels. Being able to make a cancer more likely to respond to a chemotherapy like carboplatin would be a major advance, but being able to achieve that at the same time as reducing its side-effects would be a very attractive bonus for patients already wary of chemotherapy side-effects.

That first study, the CEP-1 study, strongly pointed to IDX delivering on both counts – (i) a strong anti-cancer response in tumours that previously had stopped responding to chemotherapy, and (ii) a lower level of side-effects. CEP-1 provided a solid reason to focus on a chemo-enhancing program of IDX and carboplatin in, say, ovarian or breast cancer, two tumour types that showed encouraging clinical signals in CEP-1.

Why didn’t we stick to that path? …. simply because with any drug development program running over a typical 8-10 year period, there is always the risk of being gazumped by a better technology, and back in 2018 when we wrapped up CEP-1, immuno-oncology treatments such as checkpoint inhibitors and CAR-T cell therapy were causing a lot of excitement. There even was talk of chemotherapy being a thing of the past! As Sir Humphrey Appleby might have said, it would have been a ‘courageous decision’ to bet the farm on an eight-year development program with that risk running in the background.

In any case, from 2018 on our options began to explode.  Far from being a single-action drug, we learnt that IDX also:

  • has broad-ranging immunotherapy actions from activating cancer-killing immune cells, through to causing those activated immune cells to move around the body, producing the highly sought effect of restoring immune function to tumours (the ‘COLD’ to ‘HOT’ effect)
  • enhances the anti-cancer effects of radiotherapy
  • has potent and unique anti-inflammatory effects.

We became no longer dependent on a single mechanism of action defining a single way of using the drug. Its multi-functionality meant that we had another strategic option which was to run parallel opportunities, both as a risk-mitigation strategy as well as the opportunity to see IDX become a major first-in-class drug used in combination with all standard forms of anti-cancer therapy. This would mean some inevitable dilution of effort, and being delayed by the need to go back and run a series of Phase 1 studies for each therapeutic target. Nevertheless, this strategy carried greater certainty of eventual success and I stand by it today.

This multi-functionality means that we have been able to add to our chemo-enhancing CEP) opportunity pipeline

  • the checkpoint inhibitor option (IONIC program)
  • the radio-enhancement option, combining IDX with external beam radiotherapy (DARRT program)
  • targeted radiotherapy in the form of radioligand therapy (LuPIN program).

Importantly, all these opportunities offered strong prospects of patent protection over specific therapeutic uses – important, because IDX was off-patent and its commercial value, as distinct from its therapeutic value, lay in being granted patent claims over how it is used.

To where we are now

After 5 years, we are now at the point of reaping the benefit of all that hard work and ground-breaking science.

The opportunities have arranged themselves into 4 separate R&D streams:

Oncology - Veyonda

Oncology Pipeline

Inflammation - Veyonda


There is far too much happening across those 4 streams to go into detail, but I will pick out just three examples of what I regard as standout developments highlighting the cutting-edge nature of our science.

Example 1.

IONIC trialThe standout development here is a unique mechanism of action of IDX that we believe gives Veyonda a high likelihood of succeeding where others have failed.

Checkpoint inhibitor therapy is the current talking point of the pharma industry. Three drugs dominate the market: Opdivoâ (BMS), Yervoyâ (BMS) and Keytrudaâ (Merck) with collective sales last year of about US$20 billion.

Despite that impressive sales number, these drugs only work in a handful of cancers, and even then, only in a minority of patients. Put both of those factors together and the result is that across the full spectrum of solid cancers, these three drugs only work in a very small minority of patients.

There’s a range of reasons why most patients don’t respond, but there is general agreement that one key reason is something called ‘COLD’ tumours, or tumours lacking immune cells. Drugs like Opdivo and Keytruda don’t kill cancer cells themselves – they disarm them and render the cells more susceptible to attack by immune cells. This means that immune cells need to be present to take advantage of this… with no immune cells present, the effect of the checkpoint inhibiting drug is lost.

In simplistic terms, patients that respond to checkpoint inhibitors do so because their tumours contain immune cells; non-responding patients have tumours that lack immune cells. Tumours with immune cells are referred to as being ‘HOT’, and those without immune cells as being ‘COLD’. Hence, converting tumours from ‘COLD’ to ‘HOT’ is the big effort currently in oncology.

Several technologies are being looked at, none of which at this time appears to have stood out as being a breakthrough. It is our view that this can be put down to the fact that none, to our understanding, target the underlying cause of tumour COLDNESS. Instead, they try to fight against it.

The underlying cause of tumour COLDNESS is excessive production by cancer cells of the chemical, sphingosine-1-phosphate (S1P). This high level of S1P inside the tumour is what drives immune cells out and keeps them out.

IDX blocks the production of S1P, with laboratory studies showing that immune cells subsequently turn a ‘COLD’ tumour into a ‘HOT’ one. In our considered opinion, this makes Veyonda the only technology currently being tested that deals directly with S1P levels as a primary cause of tumour ‘COLDNESS’.

Example 2.

DARRT trialThe standout development here is an understanding that Veyonda possesses the key mechanisms needed to trigger an abscopal response.

Of all the different ways to treat a malignant cancer once it has spread, eliciting an abscopal response arguably offers safe, accessible and inexpensive  outcome of anti-cancer treatment. It typically involves about 1 hour a day for about 5-7 days at a standard hospital radiation oncology unit, with patients receiving radiation to 1 or 2 single tumours at a dose low enough to cause very few side-effects…no surgery, no toxic chemotherapy, no skin-burning like in high-dose radiotherapy …just the creation of an immune response within the irradiated tumours leading to the resolution of some or all tumours throughout the body. All using readily available standard radiotherapy machines, with a course of therapy costing thousands of dollars, not tens of thousands (chemotherapy) or hundreds of thousands (immuno-oncology therapy) of dollars.

The downside is that 50 or so years of radiotherapy experience have shown the chances of achieving an abscopal response to be incredibly low. In fact, the incidence is so rare that it hasn’t been possible to calculate, but a figure of less than 1 in 50,000-100,000 cases is probably close to the mark. So, a long way from being a mainstream treatment …yet.

A group of researchers and clinicians at Weill Cornell University in New York have led the world in trying to make the abscopal response a more common outcome. A research team led by Dr Lorenzo Galluzzi at Weill Cornell Medical College has been looking at the immune response that underlies the abscopal response – what triggers it to start with, and what ensures that it spills out of the irradiated tumour and spreads throughout the body. They found that the immune response is triggered by fragments in the cell of damaged mitochondrial DNA created by the radiation. This activates a scavenging process known as autophagy that mops up the DNA fragments.

The problem is that autophagy is just so efficient in cancer cells that they manage to remove the fragments before the immune response can gather much steam. They showed that blocking autophagy meant that the DNA fragments remain long enough for the immune response to build the strength to spill out of the irradiated tumour(s) into the bloodstream, and from there to create an abscopal response.

IDX is a potent inhibitor of autophagy. But triggering the immune response is one thing …. overcoming the COLDNESS of the body’s secondary tumours is another thing. The dual actions of IDX of autophagy inhibition and ‘COLD’ to ‘HOT’ tumour conversion are unique and we believe the key to making the abscopal response a mainstream outcome.

We saw evidence of abscopal responses in the DARRT-1 study in men with late-stage prostate cancer, and while still an impressive outcome considering the rare background rate of abscopal responses, we felt we could do better. In the Phase 2 DARRT-2 study getting underway, we have stepped up the Veyonda treatment schedule considerably, doubling the daily dose (from 1200 mg to up to 2400 mg), and the number of treatment cycles up from a single cycle to up to several cycles.

Finally, note that Dr Galluzzi and his Weill Cornell team are currently exploring ways to maximise the ability of IDX to induce an abscopal response.

Example 3.

CEP-2 trialThe standout development here is the approval by the FDA to allow Veyonda to be used as first-line treatment.

Experimental anti-cancer drugs are almost always tested in patients with cancers that have exhausted standard treatments. Once a patient is left with progressive disease after having tried all approved therapies, experimental drug trials can be a final option. While the people running clinical trials are enormously grateful for the willingness of patients to sign up to test a new therapy with no certainty of success, the challenge is that often these patients have undergone multiple lines of therapy, often with different drugs and procedures, leaving a cancer that is a lot tougher than what first appeared. This resistance goes some way to explaining the 95% failure rate of new anti-cancer drug treatments.

Over 600 cancer patients have received IDX, first in its original pre-Noxopharm form and now as Veyonda, with rules meaning that almost every patient had late-stage cancer that had become refractory to standard treatments.

The best time to treat a cancer is in its early stages before exposure to multiple anti-cancer therapies has self-selected the most resistant cancer cell clones and led to the accumulation of a range of different mutations. A greater chance of responding to the new treatment is good for the patient and good for the drug developer. For this reason, the Company was exceptionally pleased to be granted permission from the FDA to use Veyonda as a first-line treatment.

This is the basis of the IND (Investigational New Drug) grant in 2020 to test a combination of Veyonda and doxorubicin in patients with soft tissue sarcomas. These patients will not have received anti-cancer therapy beforehand.

FDAgrantsINDapprovaltoVeyonda (

Doxorubicin is the standard of care drug for sarcoma, but with generally low response rates. The IND was granted based on pre-clinical evidence showing IDX working in a way to considerably augment the cancer-killing effect of doxorubicin.



  • We took a drug idronoxil (IDX) that many had lauded early as a potential ‘breakthrough’ anti-cancer drug but was ultimately considered to be ‘unworkable’ and ‘unpatentable’. Through good science, we have resurrected that drug by learning how to make it work and, in the process, restore its patentability
  • We have re-confirmed its ‘breakthrough’ potential as a major new anti-cancer drug, having the capacity to achieve the long-held goal of a single drug capable of boosting the effectiveness of most standard forms of anti-cancer therapy, which, if confirmed, would make it an asset of extraordinary high value
  • A clinical program involving 7x trials to date, in our eyes providing proof-of-concept of that ‘single booster drug’ concept
  • An in-house drug discovery program that has yielded 3 additional exciting new drug prospects
  • Multiple pre-clinical and clinical programs that have created new IP around IDX and related molecules in the areas of cancer, inflammation and neurotoxicity, leading to multiple provisional patent applications
  • Two subsidiaries created to house some of this new IP, with one being listed on the ASX with Noxopharm retaining a major shareholding; the other (Pharmorage) scientifically and commercially aligned with Australia’s leading medical research institute in the field of inflammation
  • A clear commercial strategy.
  • All of which has built the foundations of a company that we believe is set to become a force in the global pharma industry as a drug discovery company.