Noxopharm Limited (ASX:NOX) CEO and Managing Director Dr Graham Kelly gives an update on the company and its clinical trials.
Hello and welcome to this webcast. As Clive said, my name is Graham Kelly. I'm the company CEO and Managing Director, and my aim today is twofold. The first is to introduce the company to any new shareholders that might be with us. And just to explain our objectives and plans. Also to provide an update on our activities to existing shareholders.
So, this slide really summarises what we're all about. Our primary focus is on our lead pipeline drug Veyonda, and our belief that it holds the answer to a long-term problem that's afflicted all three major forms of cancer therapy, which are immuno-oncology, radiotherapy and chemotherapy. And that problem is what is holding back the ability of all those three therapies to perform to their full potential. Something that we are confident that we can solve. Now, I'm quite open in saying that our ultimate aim is to establish Noxopharm as a highly sought after industry partner.
We want some of the industry's biggest players to understand what Veyonda can offer them in terms of boosting sales of their own products. And I've set the end of 2022, as an achievable target for that to happen, although any time before that is a possibility based on data flow from our upcoming clinical program.
Now, this slide shows what I regard as our major achievements this year, and thanks to the work of some very eminent external researchers, we learned three important things this year, about how Veyonda works. These were things that we were not aware of up until the beginning of this year. Now, one of those things is that Veyonda restores immune function to tumours. This is arguably its most important function. And it does this in a process that's called converting tumours from COLD to HOT. We'll be talking about this in a bit more detail shortly.
And this we believe provides an explanation for why we have seen some pretty exciting survival data coming out of our Lupin clinical trial, which involves a Novartis drug and separately, that information has led to Bristol Myers Squibb joining us in a joint clinical study. Now another discovery came from Cornell University and provided an elegant explanation for why we saw a remarkably high rate of abscopal responses in our DARRT-1 clinical study. The third discovery came from the Hudson Institute here in Australia, and that showed the way that Veyonda works that they believe could be a potential treatment for something called septic shock. And that provided the rationale for starting a pilot study in COVID-19 patients, and also led to the creation of a wholly owned subsidiary, Pharmorage that will focus just on septic shock.
So as we go into 2021, we find ourselves in a pretty strong cash position, thanks to the recent $23M cap raise. And that position gives us a sufficient runway, at least for the next 12 months, and we believe along with the anticipated R&D rebates, will take us into 2022, but more importantly, it puts us in a position of generating what we see is enough clinical data to confirm Veyonda as a major new drug prospect. So we set the amount of $23M purposely to achieve that particular endpoint, that is, identification or proof of concept that Veyonda is everything that we believe it to be.
So now to why we believe Veyonda is an exciting new drug prospect. The future of cancer therapy is about getting the immune system back on track to do its job and eliminate what are essentially unwanted invaders, that is the cancer cells. Now getting the immune system re-energised and back on track, isn't all that difficult. There's a wide number of successful ways of doing that. The problem lies in getting those re-energised immune cells out of the blood and where they need to be, which is back inside the actual tumours. That has turned out to be a major challenge, because the great majority of human tumours, expel immune cells, and then keep them expelled. They literally put a shield around the tumour that prevents them from re-entering. And that is a problem that faces all forms of cancer therapy, immuno-oncology therapy, radiotherapy and chemotherapy. And we believe that Veyonda can overcome that block. And we also believe it's the first drug capable of doing that.
And this slide explains exactly how it does that. Now on the left-hand side, in the green, you see a healthy tissue and the red T-cells are immune cells. And these cells basically flood all our tissues and they're continuously crawling through the tissues, looking for any abnormal or damaged cells. That's called immunosurveillance. Now part of the process of a cancer becoming established involves eliminating that surveillance function, by expelling all the immune cells. And tumours do this by making a chemical called sphingosine-1-phosphate or S1P for short. And S1P has the effect of driving immune cells out of this developing tumour, to the extent that once a tumour is fully formed, it now has very high S1P levels that serve to keep those immune cells locked outside of the tumour.And what Veyonda does is that it actually blocks S1P production. It removes that S1P from the tumour. And once you do that, the immune cells rapidly flood back inside the tumour. Now this process is referred to as converting a tumour from being COLD to HOT. And with that comes the opportunity to help shift a market worth about US$30 billion a year to over what many analysts believe is a hundred or even $150 billion potential. So it's not surprising that one of the hottest goals in the pharmaceutical industry is learning how to convert tumours from COLD to HOT, in the expectation that this is the key to gating all forms of other cancer therapy working to their full potential. So again, we believe that Veyonda is the best placed candidate to achieve that goal.
And these are the four ways that we're looking to exploit this unique COLD to HOT treatment, so we're looking at something called PD-1 therapy, which is basically called immuno-oncology therapy, two forms of radiotherapy, and then one chemotherapy. Now, while all of these four programs are active, over the next two years, we're really just focusing on those first two, the so-called IONIC program and the DARRT program.
So to explain the IONIC program, this concerns the use of a new class of drug called checkpoint inhibitors. I won't bore you with the technicality of what a checkpoint inhibitor does, but it represents a major discovery about 15 years ago, about one of the ways that cancer cells can hide themselves from immune cells. Now there's three drugs that dominate this class, Keytruda®, Opdivo® and Yervoy®. Collectively these three drugs last year, sold $22 billion worth. So they're already as a class about number two in the world, in terms of their overall sales that have been generated. You really have to go and look at things like cholesterol lowering drugs as a class to get anywhere near the numbers that have been generated by these three drugs, and given the lucrative nature of this field, not surprisingly, every major pharma company in the world is actively playing in it.
And as impressive as these drugs can be, unfortunately, across the broad cancer spectrum, they only work in about 5% of patients, of one in 20 patients. And the cold tumour problem is generally identified as being the major issue, that's preventing 5% becoming 50% or 70%. And what big pharma is doing is concentrating on developing the means to activate the immune system. As I said earlier, that's not a major problem. There are a number of ways you can do that. Biotech is tending to concentrate on the second part of the equation, which is finding ways to make those big pharma therapies work in more patients. And that dynamic between big pharma and biotech, is driving a lot of licensing and M &A activities, which is growing year on year. The numbers I've got here are for 2018, when there were 15 licensing deals, each over a billion US dollars in value. And I've just given two examples of the largest ones here, where Bristol Myers Squibb paid US$3.6 billion and Merck, even more, US$5.7 billion. That's not an ownership, that's a licensing deal.
So, the IONIC's number one study, IONIC-1 study, this was a Phase I/II study involving about 30 patients, although we're not limited to that number. It can be increased if the data justifies it. It's a study that's going to be conducted in three hospitals, and it'll involve two cohorts of patients. The first cohort are going to be patients who've been treated with Opdivo, but have failed to respond to it. So this is roughly somewhere between 70 and 90% of patients with cancer of the lung, or melanoma or kidney or bladder, that don't respond. Between 70 to 90% don't respond. So what we're looking to see is by introducing a combination with Veyonda, can we now get them to respond?
The second cohort will be patients who have a type of tumour, which are generally regarded as being completely unresponsive to drugs like Opdivo and Keytruda. And so they're not generally even used. So these are basically any other cancer, other than lung, melanoma, kidney and bladder. And so, we call those Opdivo naive patients. And all these patients will be scanned after three months to determine whether they're responding and then they'll be followed for 12 months to record their survival. Now, the overall length of the study is about two and a half years. That includes this 12 month observation period, but we will be providing a series of interim reports over that time. So the outcome will be known and reported before the end of the study. And we anticipate having at least two or three interim reports during next year.
I might just flick back to the previous slide, and just emphasise that Bristol Myers Squibb were keen to join us in this study with their drug Opdivo, for the reason that... Well apart that it works in fewer patients that it doesn't work in, Opdivo sales last year for BMS were US$8 billion, which is around about a third of their total sales. So a third of the total sales of this very large pharma company, there's one drug. And so you can see that if we could get their drug Opdivo to work in more than one of 20 patients, that US$8 billion should fairly quickly become a very major part of their annual sales.
So, this is the second program that we're focusing on for the next two years. And this is our so-called DARRT study, and the DARRT study relies on using Veyonda to boost the ability of radiotherapy to produce a very rare phenomenon known as an abscopal response, which this little diagram shows there where you take a patient with multiple tumours, you irradiate one, expecting to shrink it, but also some of the other, if not all the other tumours also respond. The basis of this is that the radiation is causing damage in a single tumour, and that damage triggers an immune response in that one tumour, that then spreads to all other tumours in the body. And it's an incredibly, highly prized clinical outcome, because it can result in a dramatic and quite durable outcome, that comes with virtually no side effects. It involves an inexpensive course of radiotherapy, and it's a treatment that's readily available in most hospitals. The downside is that it's incredibly rare, and this is something that we believe Veyonda can change, and take it from an extremely rare phenomenon in something less than one in a hundred thousand patients to something that's more commonplace, which according to our early data, suggests that we can achieve in about 50% of patients.
Now, the whole DARRT program and abscopal response relies on the use of a low dose radiation. So low dose radiotherapy is commonly used to shrink just individual offending tumours, just to relieve pain or discomfort. You don't expect to do anything more than just symptomatic relief on a temporary basis. No expectation that the treatment will have any effect on the overall cancer situation. That's not going to affect any of the other tumours. And where you do get an abscopal response, you certainly do get an overall effect, with that effect ranging from a partial response where some or most of the tumours stop growing or shrink, right through to a complete response where all tumours disappear, leaving essentially no tumours detectable by scanning.
Now, the reason we're so bullish about this opportunity is that our original DARRT-1 study, which was conducted in 25 men, who had late stage progressive prostate cancer, was designed to see if Veyonda could turn this abscopal response into something more than just an extremely rare phenomenon.
And that's exactly what we found. We believe we achieved this and this was in men whose cancers had stopped responding to treatment and who had very short anticipated survival times somewhere in the four to six months. That was their anticipated survival expectation. And remembering, we used a dose of radiotherapy that was too low to have any meaningful effect on the overall cancer, and yet we achieved an anti-cancer effect that delighted all the oncologists who were in the study and all those we've shown this data to since. And that outcome includes a very impressive four out of 15 patients recording and abscopal response. Now, this was worth emphasising because abscopal responses have been reported... We're now talking about over the last 30 to 40 years of using radiotherapy. An abscopal response in prostate cancer patients has been reported in no more than just a handful of men. In the order, we can find reports on about three to four men and in prostate cancer. And yet here we are seeing a response in four out of 15 patients. So already we looked in the one study, one small study, achieved more abscopal responses in prostate cancer than have been reported in the literature over the last 30 or 40 years.
So we decided that we needed to leverage this exciting outcome into a bigger study, and that's our DARRT-2 study, and this will be in up to about 200 patients. It will be a multinational study across Europe, North America, Asia and Australia. We're well advanced in the planning of the study and like any big multinational studies, it's a major logistical exercise, which the team has been on now for about four months. And we expect to be treating our first patient in the second quarter of next year. Now it's going to involve patients with late-stage prostate, breast or lung cancer. So we're giving ourselves the chance to confirm whether we can achieve abscopal responses across a range of different cancers, not just limit ourselves to prostate cancer. And more important, or just as importantly, we're also ramping up the dose of Veyonda, compared to our DARRT-1 study, because we believe these higher doses are going to give us a much better chance of achieving the abscopal response. So we're essentially doubling the dose of Veyonda we used in DARRT-1, and in DARRT-1, we only used one cycle of Veyonda, that's a single 14 day consecutive day treatment cycle. DARRT-2, we're going to be doing that two weeks, every month, and we'll keep doing that for six months.
Now I'm only going to briefly mention, this is our third program, the LuPIN study. This is a phase two study in 56 men with prostate cancer, that was being conducted here in Sydney by St. Vincent's Hospital. And from our perspective, the trial is now completed. The last patient was treated and the clinicians are now just measuring the effect of that treatment on the patient survival. The study uses a combination of Veyonda with the Novartis experimental drug Lutetium-PSMA-617. This was an intravenously administered drug, which is a radioactive drug. And the main effect we're looking at, apart from safety, is the overall survival. Now it's a single arm study, which means we don't have a side-by-side comparison with the Novartis drug on its own. But we do have available to us, data from other studies where the Norvartis drug has been used on its own, and the survival data we reported in our study with the combination, was reported earlier this year, by the St. Vincent's clinicians. They have been commenting very positively on our survival data compared to the Novartis drug alone. Now what I need to point out, was that data reported back in February, earlier this year, looked at two lower doses of Veyonda, whereas this trial is actually looking at three doses altogether. And the survival data already reported is using doses that we now believe are sub-therapeutic. Nevertheless, we've seen a good response from what appears to be a sub- therapeutic dose, but we're now looking forward to the survival data from the third and highest dose, our 1,200 milligram dose. And that's where we expect to see a major effect on patient survival. And that data is being reported to a cancer conference early next February. And if it's as good as we expect it to be, we would think that would effectively re-rate the company.
So to summarise, what we're looking to do over the next... Well, with the $23 million, we recently raised along with our Federal Government R&D rebates, is simply to give us the runway to prove that Veyonda and Noxopharm have something very special that will revolutionise cancer therapy and represent a major acquisition target.
So that's the end of the presentation. I thank you for listening and it just remains for me to thank you and to invite you to email me with any questions. And I do emphasise that. Any questions that you have, send to me, and they'll be answered. Thank you very much and goodbye.