AMPLIA THERAPEUTICS LTD (ATX) - Narmafotinib And Pancreatic Cancer Progress

Five complete responses in advanced pancreatic cancer should make anyone in biotech sit up. We’re joined by Dr Chris Burns, CEO and Managing Director of Amplia Therapeutics, to unpack what the latest mature ACCENT trial data really says about narmafotinib when it’s added to standard chemotherapy with gemcitabine and Abraxane and why “making other drugs work better” is more than a slogan when patients are running out of time.

We talk through the headline numbers, including an 11.1 month median overall survival signal and what “complete response” means in practical clinical terms. Just as important, we dig into tolerability: the combination appears to keep the side effect burden largely in line with chemotherapy alone, which is critical for any add on cancer therapy hoping to move into larger, registration enabling studies. We also explore how the US FDA fast track designation helps shape timelines and strengthens discussions with potential partners watching the pancreatic cancer pipeline closely.

Not every combo is worth forcing, and are transparent about that. We cover the recruitment halt in the AMPLICITY trial pairing narmafotinib with the more aggressive FOLFIRINOX regimen, why the limiting toxicity was linked to the chemotherapy, and how the broader landscape is shifting toward targeted and personalised medicines, including emerging RAS inhibitors. We finish with the commercial foundations, from key patents extending protection to at least 2040 in major markets to the next 12 months of milestones across pancreatic and ovarian cancer.

If you want clear, investor friendly context on pancreatic cancer drug development, clinical trial readouts, FDA pathways, and partnering strategy, hit play. Subscribe, share this with someone following oncology breakthroughs, and leave us a review with the one result you’ll be watching next.

Transcript

Andrew Musgrave

Welcome again to ASX Briefs, where we dive into the innovations shaping the future of medical development. And joining me again today is Dr. Chris Burns, the CEO and Managing Director of Amplia Therapeutics, which is focused on diseases with high unmet needs, particularly in fibrotic cancers like pancreatic and ovarian cancer. Chris, great to have you back on the podcast and thanks for joining me.

Chris Burns

Thank you, Andrew. Great to be here.

Andrew Musgrave

Now, Chris, we spoke a while ago, but for those investors that are unfamiliar with the ATX story, can we start by just getting a brief overview of the company?

Chris Burns

Yeah, very happy to do that. So Amplia Therapeutics or ASX Code ATX. We're a drug development company based here in Melbourne, and we're developing drugs and really focused very much on one drug for the treatment of cancer. And particularly our focus to date has been in pancreatic cancer. The drug, just to put that into context, was an Australian discovery, and we've taken the drug into the clinic and we're now in phase two clinical studies.

Andrew Musgrave

Now you recently reported some unprecedented mature data from the ACCENT trial, including five complete responses and a median overall survival of 11.1 months. So, can you walk us through the significance of these results compared to the current standard of care for pancreatic cancer?

Chris Burns

Yes, so the ACCENT trial is a trial that we've been running in Australia and South Korea. And we're giving our drug narmafotinib in combination with the standard of care chemotherapy, which in this instance is called gemcitabine and Abraxane. So, it's two drugs, and we add our drug on top of that. Our drug is given as a pill, so patients take that in the days preceding their chemotherapy infusion. And what we're looking at, we're looking at how well is the drug tolerated by patients on top of their chemotherapy, and is the drug making the chemotherapy work better? Because that's really the fundamental that we're trying to show here is that narmafotinib amplifies the activity of other drugs, hence the name of the company, Amplia. So, we make other drugs work better, if you like. We're comparing our data to historical data for that chemotherapy, gemcitabine Abraxane, when it's that's been used alone. So, our data has been very promising. So, as you said, Andrew, we've recently reported mature data. There are still patients on study, but mature data at this point in time shows that we've had five complete responses that have been confirmed. So, this means where there's absolutely no tumour apparent by normal CT scans in those patients. That's five patients achieved that complete response and maintained it for two months or more. And that's out of 64 patients. So that's a complete response rate of 8% approximately. Now, previous studies of chemotherapy alone have shown that complete responses are vanishingly rare, and you'd probably lucky to see more than sort of 0.1, 0.2% complete response rate when you use those chemotherapies alone. So, adding our drug on top of that's having you know a significant improvement in that complete response rate. The other thing we saw was this 11.1-month median overall survival. So, what this means is that from the patient starting out study to the point where they pass from the disease is a median value of 11.1 months. That mightn't sound great, but we're talking about advanced pancreatic cancer patients here where the median overall survival is normally about eight months. So, in the context of, eight months, that's if they're taking the chemotherapy, eight to nine months. So, in the context of that sort of time frame, an extra two months is a significant improvement. The last drug to be approved in pancreatic cancer for the treatment of metastatic disease in the US was approved on an 11.1-month overall survival. So, our number of 11.1 months is significant for patients, obviously. It's an extra couple of months. And it's also significant for regulators in that they've approved other drugs with that kind of improvement in overall survival. So that's all the promising stuff about efficacy and activity. I think the other point to note, Andrew, just to round that out, is that patients who are taking our drug on top of their chemotherapy really aren't showing a lot of side effects from our drug. There's a small amount of nausea, vomiting, and diarrhea. That's pretty common in any clinical study. But in terms of severe side effects, the side effect profile we see for our drug in combination with chemotherapy is essentially identical to what patients see with chemotherapy alone. So, our drugs not adding any additional burden, if you like, to patients.

Andrew Musgrave

And narmafotinib has received fast track designation from the US FDA for advanced pancreatic cancer. So, beyond the obvious regulatory advantages, how does this status accelerate your engagement with potential partners and the clinical timeline?

Chris Burns

Yeah, well, I think first of all, there are the regulatory advantages as we deal with the FDA, and I'm sure the listeners are very aware of the changes that have happened at the FDA over the last year. For us, we've not noticed anything in our engagement with the FDA. We're dealing with exactly the same people, and we get a very good engagement and good turnaround for any sort of questions and interactions we have with the FDA. So, I'm sure some of that is because we have a fast-track designation. So that is a real advantage. Obviously, that fast track designation is not awarded to any drug that's under clinical development. So, the FDA reviewed our preclinical and clinical package and felt a fast-track designation was appropriate. So that that's sort of if you like, an endorsement from the FDA of the of the quality of our work and that obviously makes it easier as we talk to potential partners about our project and about our plans for the future. And by having that more rapid turnaround with the FDA, that that better engagement with the FDA, it helps our timelines for clinical studies as well.

Andrew Musgrave

Now, on the flip side, you recently announced a recruitment halt in AMPLICITY the trial. So, what has this data told you about the safety profile of narmafotinib specifically, and what are the next steps for that combination?

Chris Burns

Yeah, look, it's a great question. AMPLICITY study was where we're combining narmafotinib with a different kind of chemotherapy called FOLFIRINOX. Now, FOLFIRINOX is also used in the treatment of metastatic pancreatic cancer. It's not used commonly in Australia, but more commonly used in the US and Europe. But it is quite an aggressive chemotherapy. We felt at the time of starting that when we started this study and started planning for the study, which is now a couple of years ago, that we were, you know, we were doing the work in ACCENT combining with one chemotherapy that's used in pancreatic cancer, we needed to look at the second type of chemotherapy, even though that chemotherapy is a more aggressive form of chemotherapy. What we've seen in the AMPLICITY study is that there were three dose-limiting toxicity events. None of those were related to narmafotinib. They were all related to the chemotherapy itself, which is consistent with this chemotherapy being more aggressive. It's not unusual for drug developers to have this challenge in combining a drug with FOLFIRINOX and the side effect profile for FOLFIRINOX, depending on the patient population, really is you know, can be very high. So, we made the decision to discontinue with the recruitment of new patients to the study. We still have five patients on study, and one of those patients has achieved a partial response, so that means a significant reduction in tumour size. So, you know, we continue with that study. Important to re-emphasize that the data that led to us to discontinue the recruitment is really around the toxicity that comes from FOLFIRINOX, not from narmafotinib itself. But importantly, the whole field of pancreatic cancer is changing. When we when we set out, there was really only two treatment options. It was gemcitbaine Abraxane or FOLFIRINOX, both chemotherapies. And as I've mentioned, FOLFIRINOX is quite an aggressive chemotherapy. What's happened in the last really 12 to 18 months is a whole new class of drugs have come out to target pancreatic cancer in a totally new way and in fact, some of your listeners probably even read about one drug, Daraxonrasib, that reported really exciting data in second-line patients recently. And so, we're seeing a shift in patient in treatment centres away from the toxic chemotherapy of FOLFIRINOX to these more targeted personalized medicines. And so, if we want to be, we want narmafotinib to be relevant for the future of treatment in pancreatic cancer, we need to do studies in combination with these newer therapies as well. So I guess what I'm trying to say is that that while the AMPLICITY trial ending because of the problems with FOLFIRINOX is you know definitely disappointing for the patients involved in the in the study, it actually does allow us to shift resources to these more personalized medicines that are presenting with really promising data and probably going to become a more standard of care in the in the coming years.

Andrew Musgrave

Now, looking at other markets, the company has been successful in securing the key patents in major markets like Japan and Europe, extending protection of your lead assets until 2040. So, how does this long-term exclusivity underpin your global commercial strategy?

Chris Burns

Yeah, absolutely. That's a really important question. Our drug, as I mentioned, was discovered at an industry academic partnership here in Australia. When we in licensed that asset, we then started looking about how we can improve and enhance the intellectual property around that molecule. And so, we've got a number of different patents that sort of act like a bit of an onion skin, if you like, around that core invention. But one of the key intellectual property pillars of that that approach is a patent that describes the form of the drug that's currently used in the clinical studies. The IP extends out to 2040 at least. We do have some patent extensions in a number of key markets. So, we've got that patent granted in the US, in Europe, Japan, India, Australia, Singapore, and other countries, and it's still going through filing in a range of other countries as well. So, it's really important for us as we talk about the commercial opportunity here to show that there's actual intellectual property protection about the drug that we're developing and the specific form that we're developing that can extend out well beyond the timeline of completion of our pivotal clinical studies.

Andrew Musgrave

Alright. Now looking at partnerships, what is the current status of any strategic collaborations or licensing discussions that you're having at the moment?

Chris Burns

Look, we've got great interactions with a whole range of pharma and biotech companies who are working in oncology specifically in that sort of gastrointestinal GI tract cancers of which pancreatic falls into. So, we've had ongoing discussions with companies for now many months. Obviously, our recent clinical data, the fact that the drug is well tolerated, and the fact that our drug can combine safely with a range of other therapies has enhanced the level of some of those discussions. And I should say, you know, I mentioned this new class of drugs called the RAS inhibitors that are changing the landscape in pancreatic cancer. You know, we're showing that our drug in in preclinical models can make those RAS inhibitors again work better and work for longer. So exactly the same kind of data we've shown in the ACCENT study when we combine with chemotherapy, we're showing that with RAS inhibitors, we can also enhance that that benefit, enhance the durability, at least in preclinical models. We think there's a really strong rationale to go into the clinic. And that's opening up again some additional opportunities for partnering and collaboration discussion. So those sort of interactions are very much underway. And you know, we'll obviously announce any developments at the appropriate time.

Andrew Musgrave

Now, finally, Chris, what are some of the major milestones’ shareholders should keep an eye out for over the next 12 months?

Chris Burns:

Well, definitely opportunities where we're combining narmafotinib with a RAS inhibitor in pancreatic cancer or indeed other cancers where RAS inhibitors are being employed is something we're very actively progressing. So that that'll be something we hope to announce in in the coming months. We've been speaking about our drug narmafotinib in ovarian cancer for quite some time now. We're making a lot of progress on initiating a study there, and we'll be announcing something hopefully in the not-too-distant future about that. So, a couple of other strings to our bow, if you like. But most importantly, we're really driving toward a registration-enabling study where we're combining our drug with the chemotherapy, gemcitabine and Abraxane, so building on the promising data from ACCENT. So, we have you know a lot of work underway at the moment. So, we'll be announcing progress on our plans and indeed our engagement with the regulators for that pivotal study over the coming months. So, it's there's a lot happening. We're a small team in Melbourne, but we're working very aggressively to drive narmafotinib to you know some key value inflections and therefore seeing that reflected in the company's market valuation as well.

Andrew Musgrave

Okay, Chris. Well, it's been great to chat again, so thanks for your time, and we look forward to further updates for Amplia Therapeutics in the upcoming months.

Chris Burns

Yeah, thank you very much for your time. All the best.

Andrew Musgrave:

That concludes this episode of ASX Briefs. Don't forget to subscribe, and we look forward to catching you on our next episode.