Healthcare Conference 2025. Our next presentation today is from Chimeric Therapeutics, and we're joined by CEO Dr. Rebecca McQualter. Chimeric is a clinical stage cell therapy company and an Australian leader in cell therapy, and is focused on bringing the promise of cell therapy to life for patients with cancer. Just a reminder on questions, if you have one you'd like to submit, do it using the Q&A box within Zoom, and if we have time, we'll get to those at the end. I will hand it over to Rebecca to kick off.
Thank you, Matthew, for having me, and thank you for your support throughout the past year. At Chimeric Therapeutics, it's a busy time. You will be aware that yesterday we announced an AUD 3.2 million entitlement offer. Those letters are coming out in the snail mail. I've been advised this morning, so please look out for those. I just want to say thank you to our shareholders for their ongoing support to make this work possible. I'll quickly share a few little updates from Chimeric, but you would have seen my webinar that we hosted a couple of weeks ago, again hosted by Matthew. I'll skip through a few things here. Just quickly, my disclaimer. As Matthew mentioned, Chimeric is a cancer cell therapy company, and we've got three assets across four clinical trials, all up and running in the U.S.
Just quickly, our investment highlights: we've got multiple clinical catalysts that are coming in the next 12 months. We have an extremely experienced leadership team, and who I'm very grateful for: Dr. Jason Litten, Dr. Stephanie Astrow, and Dr. Agathe Bourgogne, my Head of Manufacturing, making all of this work possible. We've got two first-in-class CAR-Ts and an off-the-shelf allo-NK, all with long patent life for those. As you're aware, our 52-week range has been quite variable, but we're currently sitting around just under AUD 10 million market cap. Just to refresh you really quickly, I wanted to take a minute to remind you about cell therapy.
I think we've heard a lot of different things over the past few weeks about cell therapy. I will remind you that seven cell therapies are now registered and making a lot of money in the US, and we'd like to add to those registered products in the coming years. Basically, cell therapy is where we take the patient's blood, we re-engineer them in a laboratory to fight cancer, and then we put them back into that patient. This is a one-on-one process, and this is really personalized medicine. I will remind you of Emily Whitehead, the very first patient to receive CAR-T cell therapy at the University of Pennsylvania, where our lead technology comes from. She's now an undergraduate student there, and she's actually been quite prominent in the past few weeks fighting for foundational research in the U.S.
As I mentioned, we have three novel cell therapies. Our lead asset, CHM CDH17, is technology from the University of Pennsylvania, and this is what I'll spend most of our time on today. We also have a first-in-class asset, CHM Chlorotoxin, which is for glioblastoma. I won't spend too much time on that. There's not much to update there. I'll remind you about the great results that we've had for our off-the-shelf product, CHM CORE-NK, with the two trials running at MD Anderson and Case Western. Let's dive into CHM CDH17. Just a quick refresher on the target. CDH17 is actually expressed on the surface of gastrointestinal cancers.
You can see in my picture here, I don't know if you can see my little hand mouse there, but these little green proteins are CDH17, and this is really important because when we put the CARs into the patient, we want to make sure the target is right on the surface so the CARs can engage and start to kill the cancer. This particular asset comes from the home of the very first CAR-T from Professor Carl June's laboratory at University of Pennsylvania and Dr. Wei, our inventor there. He actually worked with the clinical team to retrofit this CAR for the GI cancer group there, which we're working with now, who's our lead investigator for the trial, Professor Jennifer Eads.
We have had a few questions in the last few weeks about our animal data, and I really wanted to reinforce the sensational animal data that we have for this particular asset. This data made the cover of Nature Cancer in 2022, and this is like winning the Formula One World Championship to make the cover of Nature Cancer, a lifetime goal of most academic scientists. What we saw in the animal data is that the animals that were not treated with any of the technologies had significant growth in their cancers. Of the seven animal models that were tested, all of them that received the CHM CDH17 third-gen CAR-T completely eradicated the cancers in all of the models. Let me reiterate that for you.
If we take a look at the pancreatic cancer model, the animals that did not have any therapy, their cancer grew quite rapidly, and those that did have the CAR-T cell therapy had complete eradication of the cancer within 49 days, and that is as long as the experiments run for. We have sensational animal data. Based on this animal data, we have now moved into the clinic, and there are a few reasons why we think that this CAR will work. I will not get into the detail here. You can read this for yourself, but if you have a scientific analyst that would like to go into detail with me, please do let me know.
One thing that I will say is that the CAR is designed with two rocket boosters on the back of the CAR, and what that means is it can really come up against the solid tumor microenvironment to push through and start to engage the cancer and kill it. I am really delighted to share with you some preliminary clinical results that we have from our human studies that are ongoing. As I mentioned, we have done a lot of heavy lifting in the last two years, and particularly from my manufacturing team, to move this process from a laboratory-based process into a GMP-grade, FDA-accredited manufacturing process. I think you have heard me say a few times that manufacturing runs in cell therapy are a measure of success. I am really happy to announce that we have had five successful manufacturing runs.
We're entering into our sixth manufacturing run as I speak, and we're really delighted with this progress to move into the clinic. We now have three sites that are active and open across the U.S. The fourth site is doing its site initiation this week, and we should be able to announce that opening shortly. For the phase I portion of the phase I/II trial, we have 15 patients that we can recruit, and this is a dose escalation or a dose finding study. We do three groups of three. That's three patients at the lowest dose of 50 million cells, three patients at the second dose of 150 million cells, and three patients at 450 million cells.
Now that only adds up to nine, so we have a bit of flexibility with six extra patients to go back down or move up a dose if we need to. I am very grateful for my Chief Medical Officer for designing the trial with this type of flexibility so we can find the appropriate dose. In this clinical trial, we're targeting three different cancers. We have gastric cancers, we have neuroendocrine tumors of the small intestine, and colorectal cancer, or bowel cancer, as we commonly call it. We have dosed four patients to date. I think the last time I updated, you had only dosed three. We are really progressing and moving forward. We have patient five that is going to be dosed shortly. We have five patients that are sitting on the waiting list and ready to be screened in.
What's really encouraging about this particular trial is because there's not many advanced therapies for these particular cancers, there's a bit of a line happening around the clinical trial site. We have a lot of patients that want to be on this trial. We have a lot of clinician interest, and I've had multiple phone calls from several Australian hospitals wanting to join this trial, which is really encouraging. We hope we can bring it to Australia later in the second half of 2025, but we'll see how we go. I wanted to share with you the clinical preliminary results that we have in the three patients that we've treated so far. The first thing is our goal is to make sure that this is safe.
Now, this is the first time this has ever been tested in humans in the world, and we really want to make sure that there's no dose-limiting toxicities, that there's no off-target effects, and this is exactly what we've seen. Of the three patients that we've dosed, the first patient with colorectal cancer is lost to follow-up. What lost to follow-up means is this patient hasn't turned up for any of their scans. They were in hospital for the first 14 days of their treatment, and we know that they didn't have any dose-limiting toxicities. We know that they're still alive, but they just haven't turned up for their clinical assessments, which is really disappointing. This is a normal part of clinical trials, and this happens in most clinical trials. It's just unfortunate that this is patient number one, but we move on.
Patient two and three, really excitingly for patient two who has a neuroendocrine tumor of the small bowel, she has stable disease at day 60. Now, I know what you're thinking. You're probably thinking that stable disease is not that exciting. However, in this particular patient, if I can add some color, it is very exciting. She had a rapidly progressing neuroendocrine tumor similar to the one that took Steve Jobs' life, and typically these patients have a poor prognosis. We will dive into her results in a little bit more detail in a second. Equally, with patient number three with colorectal cancer, they also have stable disease at day 28, which is also really promising. I must remind you that this is at the first dose level. This is at the lowest dose level of 50 million cells that we've infused.
This is only after one infusion, according to the protocol. This is something that we didn't expect to see results this soon and this early, but because our inventor did such a good job of retrofitting this CAR to these patients, this is why we think we're seeing these results early. Just to reiterate, we've determined that this particular cell therapy is safe. There's no dose-limiting toxicities to date. We have not observed any off-target effects, which is very important in this case, and we've got two patients now that have stable disease. Let's move into patient number two, a 63-year-old female who had stage four metastatic rapidly progressing disease. At day 28, she showed stable disease.
At day 60, she continues to show stable disease, and this is why we're particularly excited about these results, because for a patient that's rapidly progressing, we can probably keep the cancer at bay for 28 days, but to see stable disease at day 60, we've stopped this cancer in its tracks. The cancer that we've—the tumor that we've decided to image is the one in her pelvis, and it is roughly 10 centimeters in size. What we can see on the scan is evidence of tumor necrosis, but the tumor is still sitting there. We are really keen to see her day 90 scan to see if the body has started to remove that tumor and really started to kill it, but we'll have to wait and see on that one.
What's really exciting is that we've shown that this durable response is out to 60 days, and in the cell therapy world, this is very important. One thing that I want to show you is the way that her CARs behaved in her blood. Now, I won't get too technical here and start to nerd out as a cell therapy nerd, but what I want to show you is this graph, and this is the way that the CARs performed in her blood. This is very important because this is a textbook response that we've seen in this particular patient. What we've seen is a high number of the CAR-positive cells. We've seen the expansion from the original 50 million cells, which means the immune system's been activated and has been told by the CARs to start killing this cancer.
What's really interesting is that we can see the CARs are still in her bloodstream at day 28. We're still waiting for all of her bloods to be processed, and this takes some time to make sure that we've got these results correct. Before you ask me, do we have them yet? As soon as I have them, I'll announce them. It's really important that we can see that if that flat line at the top there, if I get my little hand here, this is really important because this is the cancer killing zone. The longer the CARs stay in this flat line, the more potential we have to kill this tumor. We went looking for comparators in a solid tumor kind of space.
We had a look at the Claudin 18.2 CARs that's been developed by Lyell in the U.S., but we couldn't really see any of this activity. I think it's really important to note that we're testing a third-generation CAR with the two rocket boosters on the back, and this is likely why we're seeing this beautiful flat line and the textbook response. Before I move on, just to quickly round out the CDH17 preliminary clinical results, we've treated four patients now. We haven't seen any dose-limiting toxicities, we haven't seen any off-target effects, and we're showing stable disease at day 28 and at day 60, and this is really important in a solid tumor context. I'm not going to speak about chlorotoxin. We're trying to work on a few things there.
The trial is still active and open and running in Austin, Texas, and I'm just going to skip through this really quickly for the sake of time, but that picture looks really good on my screen there. Moving on to CORE-NK. Just a quick refresher on our off-the-shelf product. Now, this is slightly different to what we do with the one-on-one manufacturing with our CHM CDH17 CAR. For this particular asset, we can manufacture multiple doses from one healthy donor, and at the moment, we're in the middle of our second manufacturing run to complete another 200 doses to continue the trials. I want to thank my Head of Manufacturing for that effort there, and it's really important that our cells are happy and active and aggressive when they're going in to attack the cancer.
I just wanted to refresh your memory about the complete responses that we've had in this particular asset. We've had one particular patient that was infused with our CORE-NK cells who's now had an ongoing response of over four years, and that was the last update we got, and she's living her best life, which is fantastic. I think this is really important because this creates a great foundation for this particular technology. As I mentioned, we've got two trials running with this particular asset, and these trials are funded by our partners at MD Anderson Cancer Center and Case Western Reserve University, and we're really grateful for their support. We contribute our beautiful cells, and they pay for the clinical trial. Of the two trials ongoing, I'll speak about the MD Anderson trial first.
You would have seen in December, we announced that we moved from the refractory relapse patients in AML, which is a blood cancer, and now we've moved to frontline. This is a really important milestone in the cell therapy sector, and we've got a lot of interest from other cell therapy companies because we're the first company to test a cell therapy first line in any blood cancer setting. Usually in the blood cancer setting, you have to fail a couple of treatments first, but here we are testing our NK cells frontline, very important, a huge milestone, and I never thought I'd be able to run a company with a frontline cell therapy asset. We're very excited to see what they do. Cohort one was cleared. We didn't find any dose-limiting toxicities.
We didn't find any off-target effects, and we were cleared to move to cohort two. Cohort two is the frontline cohort, and these are patients who are not eligible for a stem cell transplant, and they particularly might be frail or old, and we are really going to hit them hard with our NK cells up first. I'm really pleased to say that we've dosed one patient, and we're rapidly recruiting at MD Anderson, and I'm really grateful for their partnership there. Hopefully we'll have some results from that soon, but we're moving pretty quickly through that trial because there's a lot of AML patients at MD Anderson Cancer Center. Our Case Western trial—sorry, this is our MD Anderson Cancer Center protocol. We've got our CORE-NK cells followed by two FDA-registered therapies, a chemotherapy and a blood cancer therapy.
Like I said, we've now moved to frontline, and we are giving the NK cells first. For the trial happening at Case Western Reserve University, this is a fantastic trial. We've now dosed four patients, and this is a trial with an investigational drug called Vactosertib. I'll test you on how to pronounce that a little bit later, but basically this inhibits an immunotherapy pathway. It's like adding another immunotherapy into it, and we're giving our CORE-NK cells with Vactosertib. As we announced late last year, we have had a complete response from a patient that had a blood cancer. We did see no signs of cancer in her blood at day 28, and so we're really excited about this trial.
Because we've seen these great results in AML, we will likely focus this trial on AML and think about how we're going to tackle colorectal cancer in this particular trial, but the focus will now move to AML for this trial. We've achieved a lot in 2024, and I'm really proud of our progress. What we've really shown is that we can deliver clinical trial results into humans. We've opened CHM CDH17. We've opened three sites last year. We've dosed the first patient very excitingly, even though he went missing. We've now dosed four patients in total, with the fifth patient ready to be dosed shortly. The cells have been manufactured for that patient. For 2025, the remaining clinical catalysts, we will complete the dose-finding study, and that's treating up to 15 patients.
We want to make sure that we complete phase I and get ready for phase II. We have a really fantastic clinical trial design, which means we do not have to go back to the FDA for approval. We have a phase I/ II approval already, so we can move into that phase II piece. That is actually a registrational trial for us, and we can be on the market at the end of phase II for this particular asset. For chlorotoxin, we are taking our time to redesign this program. We are maintaining our long-term follow-up requirements, and we really want to work with the team here in Melbourne to make sure that we can implement a new trial design to make it more commercially viable. Even though it is a great asset, we have to make sure there is that scale there.
For CHM CORE-NK, for the advanced AML trial that I've discussed that's now moved to frontline, we completed the dose escalation. We've moved to frontline, and we're really ticking all the boxes for our 2024 deliverables. For us in 2025, as I mentioned, we're completing our second manufacturing run to make sure we've got 200 doses of our CORE-NK product, and we'd like to complete the frontline AML trial in conjunction with MD Anderson Cancer Center. There's a lot happening at Chimeric. As I mentioned at the start, we announced yesterday an AUD 3.2 million entitlement offer, so please look out for that one. I'm very proud of our previous announcement of getting AUD 4 million of non-dilutive funding so we can continue the CHM CDH17 trial, and we're really grateful for the support of the U.S. Family Office out of America there.
With that, I will close and take any questions that you might have.
Okay, thanks very much, Rebecca. We'll jump straight into the questions, as you've mentioned. This is a bit of a multi-pronged question, but someone's asked about helping to develop a bit of an understanding of the portfolio and your priorities. There are three or four parts to this. Which of the assets is likely to progress fast through clinical trials? What's the most promising at this stage? Which one is the easiest to progress through clinical trials? What is your favorite child?
What's my favorite child? Good question. For us, in terms of our commercial goals and where we'd like to take Chimeric, we really focused on CHM CDH17, and there's a few reasons for that.
We're targeting multiple cancers, and the reason we can target multiple cancers is because they express CDH17 on the surface, if I act it out again. That market there is over $25 billion in the U.S., and it's the most rapidly growing market segment in the oncology space. Particularly for bowel cancer, we're seeing, unfortunately, the rate between 20- and 30-year-olds being diagnosed with stage four bowel cancer is significant, and this is also happening in Australia. To have a cell therapy which would help all of those younger patients and their T cells will perform really well during manufacturing is going to be a huge commercial appeal for us and any particular partners that we may be approaching. I think of my favorite children, CHM CDH17 is a lot of work, and the team are working really hard to deliver that program.
I think it has the most potential, but equally for the CORE-NK platform, because it's an off-the-shelf platform and we can manufacture doses and have it frozen in the basement of every hospital around the world, that's also got great commercial potential. We hope we can turn all of my three children into great commercial potentials moving forward, but I think the lead asset for us right now is CHM CDH17. Very good. For patient two in the CDH17 trial, when will they reach day 90? Soon. They'll reach day 90. I think we announced the results two weeks ago, so they've probably still got another two or three weeks to go. Don't hold me to that. I'll have to double-check, but we're really looking forward to that day 90 scan.
Very good. The next question is, can you please shed light on frontline therapy? How is it different from, say, standard of care?
Frontline therapy is really exciting. Typically, when you think about standard of care, you have to go through all of the horrible chemotherapies first. This is for blood cancer. This is for colorectal cancer as well. Unfortunately, the way that our health system is set up is that you need to fail these therapies first, and then you get the really expensive, nice advanced therapy.
The question that we're really asking with the CHM CORE-NK frontline trial is, okay, if we give the advanced technology first and the patient doesn't have to go through all the awful chemo, which is really taxing on the body and also really taxing on the way their immune system can perform to fight the cancer, what will be the outcome? Because our CORE-NK platform is relatively inexpensive in the cell therapy world, it's a really great kind of test in the water to see how we go. There is one other company that I'm aware of that's doing a CAR-T and an NK product together, but we'll let them do that expensive trial for two cell therapies and one patient first.
I think it's really exciting because we don't have to put the patient's body through all of that chemotherapy, and we can hit them really hard with the cell therapy first up. I hope that makes sense to answer that question, but it's very exciting because we're the first ones to do frontline as a little small Aussie biotech competing with some of the big boys over in the U.S.
All right, thank you. Can you speak to when we might see an update on the further three patients in the Case Western trial?
Hopefully we'll have an update shortly. I know that they're actively recruiting, and we've kind of sort of said to them we'd like to focus on AML given that complete response. We should have an update shortly. As soon as I have it, I'll let you know.
Thank you. Can you speak a bit about the potential to partner any of these assets in your experience in that regard?
Yeah, because of these amazing results, and I do have a lot of friends from my former job at Novartis and Amgen and Glaxo and Pfizer and you name it, we've received a lot of attention in the last few weeks since announcing these results because in the solid tumor setting, nobody's really seen this before. It's been really great to answer all these emails and requests for meetings. I think what we're looking for is a partner to help us fund to phase II and then see where we go from there because to fund phase II will be a big exercise. We're really looking forward to exploring our opportunities coming up at ASCO and at BIO in June.
We'll be making sure that we can speak to as many people as possible, but it's been really great to have all of the interest from all of the bigger companies.
Excellent. That is all time for today. Thanks, Rebecca. So appreciate your presentation and to everyone in the audience for joining.
Thank you.
Next up, we have Avecho Biotechnology, and Dr. Paul Gavin will be on at 1:00 P.M. Eastern Time for anyone who wants to join that one. Thank you.