OTCQB: INNMF | ASX: ATX
Greg Young: Hello, and welcome to the Life Science Investor Forum. On behalf of OTC Markets and our co-host, Zacks Small Cap Research, we are very pleased you have joined us. The next presentation of the day is from Amplia Therapeutics. Their session will be moderated by Brad Sorensen, Senior Equity Analyst with Zacks Small Cap Research. I'm very pleased to welcome Chris Burns, Chief Executive Officer and Managing Director of Amplia Therapeutics (OTCQB: INNMF, ASX: ATX). Welcome back, Chris. Over to you, Brad.
Brad Sorensen: Thank you very much. Glad to be here. And Chris, welcome. Glad to be talking with you.
Dr. Christopher Burns: Thanks, Brad. Nice to be here as well. Thanks to everyone who's dialing in.
BS: Thanks to everybody for being here. And let's just jump right into it, because I'm really excited. I've had the chance to do a lot of work on Amplia and research them, and I'm really excited about what we have to share with investors today. Let's start with the ACCENT study, because that's where it starts out. And you talk about the 5 complete responses, and how it deals with pancreatic cancer. Explain a little bit about that, and how significant that is, and how exciting that can be.
CB: Thanks, Brad. We have announced data from a study that's been running for the last couple of years. It's combining our drug, narmafotinib, with standard of care chemotherapy, gemcitabine/nab-paclitaxel, in metastatic pancreatic cancer. These are first-line patients. They would normally get chemotherapy. And what we've done is given patients the option to take our drug on top of their standard of care chemotherapy. And what we reported earlier this year, based on the blinded, independent central review, is that from the comparison with historical data, we saw a significantly better response. In particular, 5 complete responses out of 64 patients. To put that into context, the clinical study we compare against, which is called the MPACT study, they had 431 patients in that study. They saw 1 confirmed complete response. We've seen 5 out of 64 patients. And on top of that, we actually had an additional patient who left our study, underwent surgery, and ultimately was a pathological complete response. Essentially, 6 out of 64 patients had a complete response by independent review.
BS: Chris, could you just explain what a complete response is, for somebody who doesn't know that? Thanks.
CB: Absolutely. Thank you, Brad. A complete response is where there's no apparent tumor present across the board. It's not just tumors in the pancreas, but tumors anywhere in the body. We look at patients every two months. There were 5 patients who had a confirmed complete response, which means there were no tumors apparent at one time point, and then at a two-month subsequent to that, there were no apparent tumors. You need to see that for at least two months, and many of our patients had no tumors apparent for many months. It's essentially what you'd call a remission in other cancers. That was a really exciting output of our clinical trial. We also saw a very good response rate, 42% response rate, which includes unconfirmed responses. Again, much better than what's been reported previously for chemotherapy alone. And lastly, we saw a median overall survival of 11.1 months, which again is 2 to 3 months better than what's been reported for chemotherapy alone.
If we look at the direct comparison with the chemotherapy versus chemotherapy plus narmafotinib, we see significantly better responses across all possible measures. It was an open-label study, and it was a single-arm study, but it definitely gives us very strong confidence to move ahead with a registrational-enabling study. Just one final point is that on top of seeing these good responses, patients who are taking our drug and chemotherapy really didn't see any additional toxicity from our drug. Obviously, chemotherapy carries its own toxicities. And when we look across those adverse events that you get with chemotherapy, the patients taking the narmafotinib and chemotherapy didn't show any worse outcome in terms of adverse events. We don't think the drug's adding any burden to the patients. But the data we've got strongly suggests that the drug is improving the outcome.
BS: And I just want to emphasize, there's been a lot of media attention in the United States about a recent drug approval, that you mentioned, for pancreatic cancer. And this is in concert with that drug. It's not in competition with it, it's used with that, and that's improving the responses to that. Now that we've gotten to this point, what are the plans for the future? That's what investors want to know. Over the next 12 to 24 months, how can we get to an approval, so we can get this to patients and, hopefully, get pancreatic cancer solved?
CB: There's a dual pathway, to be honest. First of all, we want to build on that promising data we saw with narmafotinib and the chemotherapy. We've been working with the FDA on a design for a registrational study. We're pretty much agreed that's a three-part study. There's an optimization of the dose of narmafotinib; and then there's choosing that one dose; and then taking that forward in combination with the chemotherapy. To do that dose optimization, we've actually started a run-in of that work now, just optimizing the daily dose of narmafotinib. That work's already started in Australia. And once we've got that data, we'll take that to the FDA in the end of the first quarter next year, in 2027, to discuss that safety and pharmacokinetic data, to finalize the protocol for the registrational 2b/3 study.
Prior to that, we'll be also speaking to the FDA. We've got a meeting scheduled later this year, where we'll be talking to them about some safety and pharmacology data. We've got a couple of FDA interactions. And it's worth noting we have Fast Track designation from the FDA, so we have a really good interaction with the team there. That's the first thing we're working on, the registrational pathway. We've already started a run-in in that program. And then finalizing the protocol with FDA input over the coming months.
Then in parallel, we're actually looking at combining narmafotinib, based on the safety and tolerability that we've seen in patients, with this new class of drugs called RAS inhibitors that are being developed in pancreatic cancer. And we're talking to a number of parties about opportunities there. Nothing that we can formally announce in pancreatic cancer. And we did announce last month a relationship with Eli Lilly. Lilly have a RAS inhibitor that they're developing in non-small cell lung cancer. That's a drug called olomorasib. It's in phase three, two phase three studies now, in non-small cell lung cancer. And we're about to start a study where we combine narmafotinib on top of olomorasib. And based on our preclinical data, and in fact, a lot of scientific evidence, we strongly believe that the FAK inhibitor and the RAS inhibitor, be it olomorasib in non-small cell lung cancer or be it another RAS inhibitor in pancreatic cancer, will enhance the durability of that response. And it does that by blocking resistance pathways that we know develop in the presence of RAS inhibitors.
That's our second arm. First arm, combination with chemotherapy. Second arm, combination with RAS inhibitors. And the first time we're testing a combination clinically with a RAS inhibitor is actually not in pancreatic, but it's in lung cancer. But it's an exciting collaboration to be working with Eli Lilly. And that's a fabulous drug they've got, olomorasib, and we're excited about that combination potential.
BS: And I think it shows what the promise of this is, because Lilly wanting to team up with somebody for this, that's a pretty significant step. I know quite a bit about Lilly, too. I do want to go back, just really quick. You mentioned the dosing, finding the optimal dosing. What was the dosing for the original study? And then, if you increase the dosing, do you speculate that the results could be better? Just tell us a little bit about that.
CB: Absolutely. Short answer is, yes. We do think we can do better. The original study was run using intermittently dosed narmafotinib. Narmafotinib is a drug, it's presented to patients as a capsule. Patients take it orally. And the way we designed the trial was really built on some preclinical data that indicated that patients should take the drug in the days preceding chemotherapy, but then not take the drug in between the chemotherapy. They'd take the drug, they'd get chemotherapy, wait a few days, take our drug, then chemotherapy, wait a few days, like that. Since we started that trial, we then did a lot of further preclinical studies. We saw how well the drug was tolerated by patients. And really, we want to shift from that intermittent dosing regimen of narmafotinib to a daily dosing regimen. We believe that'll lead to better patient outcomes, in terms of durability of response and depth of response, though we already see pretty good data there, as we've discussed.
But it's also more convenient for patients. You just take our drug every day, get your chemotherapy when your oncologist tells you to get your chemotherapy, but you're taking our drug, which we think, based on all the preclinical work we've done since initiating the ACCENT study, will lead to better outcomes. We've seen great outcomes. As I said, the 5 complete responses, a complete response rate of 8%. We think we can improve on that by going to daily dosing.
BS: I think that's great. I look forward to seeing those results, and I certainly hope and believe that would be true. And you mentioned, going back to the Lilly partnership, that the KRAS inhibitors and the KRAS cancers, it's the lung cell cancer that you're working with them. But I'm guessing that that's just a starting point. And you believe that this might lead to other KRAS-type cancer.
CB: Combinations. Absolutely. I'm sure many of the audience will be familiar with KRAS inhibitors. But KRAS is a mutant protein. It's overexpressed in a number of different cancers, but most notably pancreatic cancer, colorectal cancer, and non-small cell lung cancer. There's two drugs approved in non-small cell lung cancer already that target the KRAS protein. That's sotorasib and adagrasib. Those drugs have some efficacy, but they've got a lot of toxicity associated with them. There's this next generation of drugs coming through in non-small cell lung cancer, and the Lilly drug, olomorasib, is one of those. We're combining with that drug in non-small cell lung cancer. But there's other RAS inhibitors that are being developed in pancreatic cancer and in colorectal cancer. We're talking to potential partners about those combinations. What's important, though, is that the mechanism of resistance to RAS inhibitors seems to be common regardless of the cancer. The same kind of resistance processes that we see in non-small cell lung cancer also occur in pancreatic cancer, also occur in colorectal, and indeed other KRAS-driven tumors. We think what we can learn from the collaboration with Lilly about combining narmafotinib with that Lilly KRAS inhibitor, we can translate that knowledge to combining with other RAS inhibitors in other cancers.
BS: That's excellent. And you actually described it to me in a very simple way, and how it works with chemotherapy. I don't know if you want to do that here, just to give them an idea of why it works. It made a lot of sense when I was talking about it, for somebody that's not intimately involved with this process; that helped understand why this really helps.
CB: Sure. We launched straight into the data, and I didn't really explain how the drug works. It targets a protein called Focal Adhesion Kinase. That protein is overexpressed in pancreatic cancer and, in fact, a lot of solid tumors, lung cancer, and so on. That protein's involved in resistance. It's involved in cancer cell survival and migration. But it's also involved in making a scar tissue that sits around solid tumors and protects them from attack by the immune system or attack by other drugs. And so what our drug does is it actually breaks down that fibrosis, that scar tissue, so you're actually allowing more drug to penetrate into the cancer cells. Once the chemotherapy or the KRAS inhibitor's into the cancer cells, our drug, by inhibiting FAK, blocks some resistance pathways that develop over time. It has, what we like to say, a one-two punch on cancer. There's a punch on that microenvironment, that area around the tumor; and there's a punch on the cancer cells itself. And when you combine that with a toxic therapy, like a RAS inhibitor or chemotherapy, you get this double whammy and a better therapeutic outcome. We've shown that in many preclinical models. And now we're starting to see that data clinically.
BS: That helps a lot, because I think a lot of people have had experience with those kind of cancers, and why is it so hard to treat? Well, that's one of the reasons. And this breaks down that in a big way. I also note that you're moving the drug into research for ovarian cancer. Do you want to address that process, and why you decided to do that?
CB: I'll elaborate a little bit on that. Thanks, Brad. Because I think ovarian cancer has a lot of similarities to pancreatic cancer. Many of those cancers are highly fibrotic, so they have this scar tissue. But there's also a very, very clear association with the severity of the disease and the level of this FAK enzyme in ovarian cancer. It's elevated in ovarian cancer, and the levels of that enzyme increase as patients go through their therapy, clearly indicating that FAK is involved in resistance and, ultimately, unfortunately, cancer progression. We have preclinical data. There's a lot of data in the scientific literature showing that by inhibiting the FAK enzyme, you resensitize cells to chemotherapy, be it platinum-based chemotherapy that's widely used in ovarian cancer or, indeed, more traditional cytotoxic therapy. We've also shown that we resensitize ovarian cancer cells to PARP inhibitors, and that's now a major treatment for ovarian cancer.
What we're looking at in this particular study is combining our drug with chemotherapy for patients that are not responding to chemotherapy in first line. Unfortunately, a lot of patients in ovarian cancer will get chemotherapy before surgery. Most of those patients will go on to successful surgery, and then into maintenance with PARP inhibitors. Unfortunately, there's about 20% of patients who don't respond to that initial chemotherapy. And we believe, based on our preclinical data and all the scientific literature, that by adding the FAK inhibitor on top of the chemotherapy, we can improve the likelihood of response and therefore give those patients more chance of getting to surgery.
I should say, this is a small study being run here in Australia. But we're working with one of the best clinical trial not-for-profit groups associated with ovarian cancer. It's the Australia New Zealand Gynaecological Oncology Group. There's a Gynecologic Oncology Group in the US, GOG. We're working with the Australian version, and this is an investigator-sponsored study that they're running. We're supporting that, obviously, with supply of drug and additional financial support. But it's a project they're running. But we're really excited about it. We're not doing it ourselves. We can't do everything. We're only a small team here in Melbourne, Australia. Our team's primary focus is the pancreatic work and the work now that we're doing with Lilly. The ovarian work will be run out of ANZGOG. But we're excited about that opportunity. And we think, based on the science and based on the fact that there's another FAK inhibitor already approved from Verastem in ovarian cancer, that there's a real opportunity here that we want to explore.
BS: I understand that. And these groups like Lilly and the Australian gynecology group wanting to work with you shows, I think, a lot of confidence in what you guys are doing. But you brought it up, and investors are going to wonder, what is the financial picture? This costs a lot of money to bring things to the commercial stage and to do the testing. And people always wonder how much dilution is there going to be, how many shares are going to have to be offered? Are you going to go into debt? Just explain what the situation is and what it looks like over the next couple years as you go through these processes.
CB: Thanks, Brad. At the last quarterly financial update, we had AU$24 million in the bank. That money is being deployed on the first stage of the ACCENT registrational study that I spoke about, that we're running here in Australia. It's also supporting the Lilly collaboration. Both of those are now fully funded. We're finishing off the ACCENT study. We're doing all the regulatory work, engaging with the FDA. All that work's covered by existing funds. We do have discussions with some regional partners to look at some regional partnering opportunities. Those discussions continue. They would obviously bring in some money. But the reality is that running a pivotal study in pancreatic cancer is expensive and will take a number of years. We will be looking to raise money in due course. I can't say much more than that at this point in time, but we definitely have funding that gets us well into 2027 at the moment, and definitely supports the Lilly and the first part of the ACCENT clinical study that I've spoken about today.
BS: And I work with a lot of clinical-stage biotech companies. And being funded through next year, that's a pretty good stage. There's not a lot of companies that do that. Go ahead.
CB: Sorry, Brad. I just wanted to add, we've been running the development out of Australia. We're at the point where we are now, which is mid-stage clinical studies heading into Phase 3 studies, and we've done all that, based on US dollars, about US$50 million. We've run this program in a very lean way. We continue to do that. We've only got a small team of a dozen, literally 12 people, on our team, and we work with a fabulous group of collaborators and contractors. But we do run very lean and mean. And we'll be looking to continue that mindset as we take the drug into the pivotal studies.
BS: That's great to know that you're paying attention to that, and that helps get those studies further along with the same funds that you have. I'm going to finish with this overall broad question. This will let you talk about things that maybe I haven't mentioned that you want to talk about. Just think in the next two, three years, for investors that want to look at Amplia, and I encourage them to do that, what should they be looking for? If everything was executed well, what the next two or three years look like? And what would enhance investor value in the next couple years?
CB: As I said, our primary focus is in pancreatic cancer, and we continue to drive forward in that space. I think the key interactions with the FDA over the next six months are worth noting. And then as we prepare for that registrational study, which would start sometime in 2027, second half of 2027, we believe that study will start then. We'll have early data from the first part of that study that we're doing now. That's something to watch. And we strongly believe that there's an ongoing role of chemotherapy in the treatment of pancreatic cancer. I think all the data would indicate that chemotherapy is an integral part of the treatment landscape. Nevertheless, we're very conscious of what's happening with KRAS inhibitors. And we've started the work now with Lilly, looking at a combination with their KRAS inhibitor. But obviously, we're very interested in combinations with KRAS inhibitors in pancreatic cancer.
You look at companies like Revolution Medicines, like Erasca, and others, they've got very high market caps on the back of their exciting clinical data. We think that there's a real opportunity for Amplia to enhance the efficacy and prolong the duration of response to KRAS inhibitors. And a company like Tango Therapeutics is probably a good comparator because they have a drug that is being tested in combination with KRAS inhibitors in pancreatic cancer. Their drug works, maybe, on 30% of patients with pancreatic cancer. Our drug works regardless of the kind of genetic makeup of the pancreatic cancer. We think we can really ride that wave of enthusiasm and excitement around KRAS inhibitors, by combining with them, making them work better, and building out that data set. That's something that, I think, investors will want to be watching closely over the next 12 months. We're starting the Lilly collaboration. We're talking to other parties about combinations with KRAS inhibitors in pancreatic cancer. And hopefully, we'll have something we can announce in the shorter term about that.
BS: Excellent. I said that was the last question, but I have one more. I know that the FDA has certain programs that fast track some drugs, as they see good results and it's an urgent need. Is that something that you don't know, the FDA just tells you when they decide it? Or do you get a feeling about it? Is that a thing that's in the cards?
CB: We already have Fast Track designation from the FDA, which is great. We've got Orphan Drug designation as well, which gives us extended marketability, exclusive marketability of the drug. We're talking, also, to the European regulator about similar schemes in Europe. As we develop our data set, we'll go back to the FDA and look for additional pathways, Breakthrough designation or accelerated approvals. That's ongoing, obviously, as we generate clinical data. Yes. We're definitely thinking about those opportunities and those ways of moving the program faster to a point where we can actually get registration. That's something we're very active in. We're active in talking to pharma and biotech partners who we can work with to help progress the drug as well. Very much across those opportunities.
BS: I knew that you had those. I wanted to make sure investors knew that, because those can be very valuable to companies. And they don't give them out to everybody. Well, we're about at the end of time. I know that you have in front of you, I'm sure there's a lot of questions that have come in. You have about a minute or two. You can either choose to answer a couple of questions or just summarize what you want. It's your show right now.
CB: Thanks, Brad. I'll just finish up. There's a few questions coming in around the mechanism of the drug and how it will work in combination with KRAS inhibitors. Let me reiterate there that a KRAS inhibitor is a very powerful drug in treating cancers. And what we see is that when you block the KRAS signaling, cells often rewire. And when they rewire to get around that KRAS inhibitor, the signaling involves FAK. By blocking FAK and KRAS, you're getting a double hit on those cells. And that's data that we've got ourselves, we're really digging into that deeply. But it's data that other people have shown preclinically, and indeed, clinically. I think the rationale is very strong there. I can come back to individuals with answers to those questions. But I thank everyone for their interest. And thank you, Brad, for the questions today.
BS: Thank you. And thank everybody for listening. We appreciate it. And like you said, Chris is available for questions, and he'll get back to you, and for individual meetings if you're interested. Thank you very much for joining us.
CB: Thank you, Brad.
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