Noxopharm Limited (ASX:NOX) Executive Chairman and CEO Dr Graham Kelly and Chief Medical Officer Dr Gisela Mautner discuss ASCO 2020 Clinical data.
Dr Graham Kelly: Hello, and welcome. My name is Graham Kelly, and I welcome you very much to this webcast. The purpose of today's talk is to talk about some Veyonda clinical data that was presented at the recent ASCO Conference, to try and put that data into some sort of perspective. The oncology field is alive with a lot of new therapies at the moment, all of which are creating a tremendous amount of background noise, and that makes it really quite hard for shareholders to work out exactly where a new therapy such as Veyonda stands. It can even be hard for people like me who live and breathe this business.
One of the big benefits of ASCO is it is the largest gathering of oncologists in the world, and for that reason it's become the main arena for companies to report on progress with their new therapies. So, it provides a very useful yardstick in measuring where a company's new therapy stands.
So, this is the question we're posing today, and I invite you to stay with this webcast to find out the answer. Now, I'm going to be joined today by Dr Gisela Mautner, the company's Chief Medical Officer, who you will hear from shortly.
To understand the question we're posing, you need to understand the different stages of prostate cancer. In this graph, we're looking at the three main stages of prostate cancer, starting from the time a man is diagnosed as having an aggressive form of the disease. It's worth pointing out at this stage that we're really only talking today about the 1 in 10, that's 10 per cent of men, who are diagnosed with prostate cancer, who go on to develop a form of cancer that is potentially lethal. In most men, the cancer is so slow-growing that it's very unlikely to ever be a problem. So, this graph is about the men whose cancer has spread away from where it started in the gland, and where it is now growing in an aggressive manner.
The disease process, as you can see here, can be broken into the three stages of early stage, advanced stage, and then end stage. Early stage involves treatment such as surgery, radiotherapy, and chemical castration therapy, which is designed to deprive the cancer of the male sex hormone, testosterone, which is the main driver of the growth of prostate cancer. These treatments at this early stage, can hold the cancer for up to two to three years for most men, but then it eventually starts growing again, and at this stage it's usually spread away from where it started, and the patient now is considered to have advanced disease. Treatment here is with chemotherapy drugs, and drugs that try and shut the cancer off from even the tiny amounts of testosterone left in the body. But once these treatments fail, the man now enters end-stage cancer, where the treatment is palliative, simply meaning that the treatment is designed to make life as comfortable as possible in the lead-up to death.
There was some 120 presentations this year at ASCO for prostate cancer trials of new therapies, and overwhelmingly, these trials concern the advanced stage of cancer, meaning that this is a very crowded space that Noxopharm has no interest in being involved in.
The only truly new therapy on the horizon for men who have failed all existing treatments is the experimental drug known as Lutetium PSMA-617. This is a radioactive drug that is injected intravenously, and has the aim of delivering a small dose of radiation to all secondary tumours throughout the body. That is, it's able to deliver radiation to the vast bulk of tumours in a man's skeleton, where you just cannot do that with the traditional forms of externally delivered radiation. The drug, Lutetium PSMA-617, is owned by Novartis, and is showing considerable promise. In fact, a large phase three study in some 700 men is currently underway, and is expected to read out early next year.
Noxopharm is pursuing two forms of therapy with Veyonda. The first of these involves combining it with the Novartis drug, with the aim of lifting both the response rate and the durability of the response rate to the Novartis drug. This is our so-called LuPIN program that Gisela will be talking about shortly.
The second form of therapy is our so-called DAART program, and this is our priority program. This program fits somewhere on the border of a last line therapy and palliative therapy, and to the best of our knowledge, we are on our own in this space.
So, to summarise, a very crowded conference presentation agenda. There are a number of promising new therapies in the pipeline. Overwhelmingly, these are in the middle advanced disease stage, and almost all are quite a few years away from being proven or coming to market. The most likely treatment that we see coming to market in the near term is the Novartis treatment, the intravenous radioactive drug.
So, I'll now hand over to Dr Mautner to explain to you the LuPIN and the DAART clinical data. Thank you.
Dr Gisela Mautner: I will now briefly take you through the DAART-1 study and its results.
DAART-1 was a phase one study which was designed for proof of concept. The 26 study participants were men with late-stage prostate cancer, which means the cancer was metastatic as well as castration-resistant. You can see on the right side of the slide what metastatic disease looks like. All the black dots are metastasis or secondary tumours. Now, the treatment regimen in our DAART-1 study was low dose radiotherapy administered over five days to one or two tumours, and in addition, 14 days of Veyonda, which started with a dose of 400 milligrams for the first treatment cohort, and then increased to 800 milligrams and 1200 milligrams for the second and third cohort respectively.
We have presented several important results. The first and foremost result was that Veyonda turned out to be safe and well-tolerated, which means that it had very few side effects, and the side effects were easily manageable. Now a good safety and tolerability profile is of course not only important for patients and their doctors, but it is also a very important aspect in the eyes of any regulatory authority.
The next important result was the PSA response. PSA stands for Prostate Specific Antigen, and the definition of a PSA response is that the PSA measurement has to drop to half the level or less than it was at the beginning of the study. Now, in our study, we had five patients out of 16 who had such a PSA response. Now, this result was measured at the last follow-up clinic visit at six months. This means that the treatment which the patients received in the first months of the study continued to have an effect half a year later.
Another important endpoint we measured was pain. The level of pain was measured with a standard and validated pain questionnaire, and the determination of whether there is a clinically significant improvement in pain was made when the pain score dropped by 30 per cent or more. In DAART-1, we had 10 patients out of 16 who had a clinically significant improvement in their pain. Again, this was at the last study visit at six months, which shows again the sustained treatment effect. Furthermore, four of the patients had actually become completely pain-free.
Last but not least, we examined the tumour size of the patients with CT scans, and measured them with a score which is called RECIST. Out of 15 patients that had a CT scan after six months on the study, 10 patients had either stable disease or a partial response. This means that their tumours had not grown for six months, or even reduced in size over the period of time. What was even more remarkable was that four patients showed an abscopal response, which means that a tumour that was outside of the radiation field and had not received any radiation treatment has shrunk. Such an abscopal response is a rare and certainly very exciting occurrence.
Our next trial will build on our experience and the positive results that we achieved in our DAART-1 study. With our upcoming trial, which is not surprisingly called DAART-2, we will enter the next stage of clinical development, as this will be a phase two trial with many more patients and more countries involved. We have already firmed up the study design, and we are now in the process of vetting the clinical research organisation who will support us with the implementation of the trial. We anticipate that we will have most regulatory submissions finalised by the end of the year.
The second study that was presented at ASCO this year was the LuPIN study. This study evaluates the radio pharmaceutical Lutetium PSMA-617 in combination with Veyonda. Now, the trial is still ongoing, so these are interim results of the first 32 patients out of a total of 56 patients. The most important result that was reported is the overall survival endpoint. The median overall survival was 17.1 months, and this was a remarkable result as it was about twice as long as you would clinically expect in these end-stage patients.
This brings me to our overall clinical strategy for prostate cancer. Our main objective is to develop a comprehensive clinical data package that is optimised for attracting future commercial partners. At this point, we have already successfully finished our phase one program, and while the data of our LUPIN trial will continue to mature, we are already, as I mentioned, deeply involved in preparing and developing the next trial. All these activities will ensure a continuous news flow and a growing data set to support the regulatory approval of Veyonda.
Dr Graham Kelly: Thank you, Gisela. It's actually quite unusual for a company to be developing two forms of treatment with the same drug for the same stage of disease, but that's the benefit of a drug such as Veyonda with its different anti-cancer functions. And in terms of which is our preference, DAART or LuPIN, the answer is that they're both our favourites. We're not playing favourites. We see both treatments as being complementary and not competitive. And we believe it'll come down to a situation where either treatment option will be selected on the basis of the patient's disease status, or individual circumstances, the treatment history, access and availability of different resources -- these will all dictate which of these two treatments might be used. And, in fact, it's quite possible that they'll be used consecutively.
Now, we have prioritised DAART, and that's simply because we really have to put our major effort into one particular program, and we see DAART as being a considerably less expensive or more cost-effective treatment, certainly more accessible, apparently with fewer toxicities. Not that the toxicities associated with the LuPIN program are serious, but there certainly are some mild toxicities there. And what the DAART does offer, as Gisela has pointed out, is the opportunity to get abscopal responses.
Now, another very key point is that DAART does not require dedicated nuclear medicine facilities. Nuclear medicine facilities are not available in all hospitals, whereas external beam radiotherapy certainly is found in most hospitals throughout the world. And the other thing that's important is that DAART, we believe, is applicable to a wide range of solid cancers, not just to prostate cancer, which is where LUPIN finds itself. So we see our current DAART program as providing two benefits. One is that it does provide us, hopefully, with an effective last line of therapy for prostate cancer patients, but also that it provides a proof of principle, where we might then take this form of treatment into other forms of cancer in due course.
So now to answering the question we posed earlier. And my answer is this, that we believe Veyonda is delivering the clinical signals and safety signals capable of leading to it becoming an important new therapy for men with prostate cancer. And based on the evidence presented at ASCO 2020, it would appear to hold a prominent position as a first-in-class last-line treatment for end-stage prostate cancer. So, here is a glimpse of the prize we are chasing. These are the three most recent deals done in the prostate cancer space, with the dollar amounts you see there reflecting the need and the market sizes. This is a very large area of current activity in the international pharmaceutical industry.
So, that just leaves me to thank you for listening to this webcast, and I do hope you've enjoyed it, and please feel free to email me or contact the company with any questions you might have. Thank you.