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An Investment in Biotech: Part 2

 

The IDX backstory (2009-2016). The birth of Noxopharm

Ironically, Noxopharm owes its existence to the failure of the OVATURE study.

 

The IDX backstory (2009-2016). The birth of Noxopharm

Ironically, Noxopharm owes its existence to the failure of the OVATURE study.

OVATURE started in 2008 and was abandoned in 2010 because not enough women showed any response to IDX in its oral dosage form, disappointing a lot of patients, scientists, oncologists and investors.

This was a failure that hit hard, and despite being out of the Company (Novogen) at that time, it still left me wondering why. After a lot of reading, I finally formed the view that the problem lay with the rapid elimination of IDX by the kidneys, with the result that the drug was not staying in the body long enough to work. We had known about this fairly rapid elimination for some time but given that most chemotherapy drugs only spend short periods of time in the body, the advice of eminent university professors had been that this should also apply to IDX. But it remained an open question because of how IDX worked. Unlike chemotherapy drugs such as carboplatin that only need to be in the body for shorter periods to exert their poisonous effect, IDX isn’t a poison…it isn’t permanently damaging and disabling the its target like a chemotherapeutic might …. IDX is simply turning off the ENOX2 pump. Remove the IDX and the pump will restart.

My eventual theory was that IDX needed to be kept in the body on a virtually constant basis if it was going to work properly, and that meant coming up with a way of keeping it in the body longer, much longer than the 1 hour that oral dosing delivers. I subsequently came up with a theory involving delivery by suppository, but I had left Novogen in 2006, and so with no access to laboratories, I was in no position to do any research.

And that should have been the end of the IDX story with IDX likely consigned to oblivion.

But Fate intervened ….not quite the sort of Fate you want to encounter, but a Fate that in retrospect I nevertheless am very glad came along.

I was diagnosed in early 2008 with inoperable prostate cancer, something of an irony for someone who had spent many years researching this form of cancer, and who was a very vocal advocate for men over the age of 50 having regular prostate health checks, which I hadn’t.

Four years of high dosages of radiotherapy and androgen-ablation therapy followed, only to be diagnosed in early-2012 with metastatic castration-resistant cancer with a number of tumours identified in my skeleton.

So, suddenly my ponderings about how to keep IDX in the body were more than academic. I had metastatic disease, with a PSA level (and tumour load) that was doubling every 6 weeks.

With little time to play with, it was time to put the theory to the test. Working in conjunction with a local formulating chemist, trial and error eventually led to a suppository dosage formulation that worked, stabilising the cancer for 2 years. A PSA level that was at about 60 and doubling every 6 weeks suddenly flat-lined within a week of hitting upon the right dosage formulation.

But by early 2014 the cancer had returned, this time back to its original level of aggression and with extensive secondary disease in the spine, skeleton and lymph nodes. I was in lots of pain and my legs were becoming progressively paralysed from the spinal tumour. A radiation oncologist prescribed a low dose of radiation to the spinal lesion to try and salvage leg function. I took that opportunity to combine the radiotherapy with 2 weeks of IDX treatment. A scan 2 months later showed complete remission of all tumours – not just the irradiated lesion, but all lesions.

That was the last treatment I had. Five years later (2019), an undetectable (<0.01) PSA level and a normal testosterone level means I experienced a phenomenon known as a complete abscopal response. Meaning complete eradication of all cancer cells, which I don’t expect ever to see return.

Why do I think IDX worked?

Because I had slowed down its excretion from the body, and that meant it stayed in the bloodstream most of the day, which meant it was available to keep the ENOX pump permanently switched off.

What I had come up with was a delivery technology we finally called LIPROSE. It is a suppository formulation that presents IDX to the body in a way that prolongs its exposure in the body significantly which means that one suppository morning and night is enough to ensure 24-hour coverage. This new drug is called Veyonda®.

Noxopharm has a suite of patents around the LIPROSE technology and the pharmacokinetic effect it produces, in some 80 countries.

  1. How do I think IDX caused an abscopal response?
    I think it worked in concert with the radiotherapy to trigger an immune response that led to the immune system eliminating all cancer cells throughout the body. In effect, I vaccinated myself against the cancer.

The growth of a cancer represents a failure of the body’s immune system. The immune system is perfectly capable of attacking and killing the cancer cells, but it is prevented by the cancer from doing so. The cancer cells in essence are thumbing their noses at the immune system.

Which is why cancer therapy in recent years has started to swing away from the indiscriminate poisonous approach, to trying to manipulate the immune system to do its job.

One way that cancer cells fool the immune system is by expelling most or all of the immune cells from the tumour …. with few or no immune cells present in the tumour, the cancer cells are free to grow completely unbothered. These tumours are referred to as COLD tumours, simply meaning that in the absence of any defence cells, the cancer isn’t triggering any inflammatory or immune activity.

I think what happened in my case is that the radiotherapy caused enough damage to inflame the irradiated tumours, with that inflammation bringing in inflammatory and immune cells to result in a so-called HOT tumour. And IDX combined with that inflammation was able to super-activate the immune cells so that they not only eliminated all cancer cells within the now HOT tumour, but spilled over into the bloodstream to seek out and destroy cancer cells throughout the body, where IDX was waiting to help them.

Sometimes, very rarely, where we believe an immune response has been triggered by radiotherapy and converted a COLD tumour to a HOT tumour, that immune response goes beyond the 1 or 2 tumours receiving radiation, reaching out to tumours well outside the field of irradiation, and resulting in them shrinking or disappearing just like the irradiated tumours. This is known as an abscopal response from the Greek ab - away from and scopus – target. An abscopal response can be partial (only some distant tumours shrinking or disappearing) or complete (all tumours in the body disappearing). My response was a complete abscopal response.

An abscopal response is an extraordinarily rare event, and based on the miniscule number of clinical reports in the medical literature, possibly a 1 in 10 million phenomenon.

Based on what we now are learning about the mechanism of action of IDX, particularly its effect on the immune system, the most likely scenario is that IDX is combining with radiation to super-charge the immune system to elevate the chances of achieving an abscopal response.

Noxopharm

Noxopharm had to be created …… I needed to answer the question whether my experience was a 1 in 10 million phenomenon unlikely ever to be repeated. Or whether it was the start of a transformative treatment regimen capable of forever changing the face of cancer therapy.

The answer is that it is being repeated. Whilst we have not yet seen anyone have quite the profound response that I did, we have seen some patients deriving meaningful clinical benefit from the regimen – although unlike me these patients have only received one short course of Veyonda®. These findings come from the Company’s DARRT-1 clinical study that is underway in men with late-stage prostate cancer.

DARRT-1 is an early-phase dose-finding study enrolling men with Stage 4 prostate cancer that has progressed to extensive secondary disease, with multiple (potentially dozens) prostate cancer tumours throughout their bodies.. It is delivering a low dose of radiation just to 1 or 2 of those tumours, at the same time as giving the men IDX in the form of Veyondaâ. Then we are following those men to see what happens to their tumours, both irradiated and non-irradiated.

We are starting with late-stage prostate cancer for obvious reasons. But we have every reason to believe that if it works in prostate cancer, it will work in a wide range of other cancer types including the common cancers like breast, lung, ovarian and colo-rectal.

Clinical data emerging from studies such as DARRT-1 over the next 6 months should reveal whether Noxopharm has the means of replicating the rise of companies like Amgen and Genentech from their humble beginnings.

……….

The next piece in this blog series will look at the DARRT program in more detail.