ASH meeting, as well as new data showing Azer-cel's efficacy in CAR T naive niche indications. Joining us from Imugene today, we have the CEO and Managing Director, Leslie Chong, and the Chief Medical Officer, Dr. John Byon. In terms of the format, there'll be an initial presentation that will last for approximately 15 or 20 minutes. Following this, we'll take questions, so if you have a question you'd like to submit, please type it in using the Q&A panel within Zoom, and we'll get to those later on. Leslie, I'll hand it over to you.
Thank you, Matt. I'm going to let our John Byon, our Chief Medical Officer, review the data. Thus far. John?
Thank you, Leslie. Okay, next slide, please. So today we're going to talk about Azer-cel, our allogeneic CD19 CAR T cell therapy for patients with lymphomas and other CD19 B cell malignancies. So as just an introduction, I just wanted to remind the audience that the type of CAR T cells that are currently approved around the world are autologous, meaning these cells are manufactured from the patient's own blood. So you can see in the top panel, the patient's blood is collected, it's sent to a manufacturing facility where it's genetically modified and reprogrammed to express the CAR on their T cells. And this process can take several weeks before it's then shipped back to the patient's treatment center and can be given to the patient. So I think on average, this is about four to six weeks in the United States.
We are developing what is called an allogeneic cell therapy, which means we collect cells from healthy donors ahead of time, perform the genetic modification required to create the CAR T cells, and then these are frozen and held at a supply facility. So when the patient presents either at the clinic or the hospital and is ready to receive Azer-cel, it can be shipped to their location within a matter of days. So this Azer-cel has multiple advantages. Primarily the number one being available on demand, so patients don't have to wait because during this waiting period these patients are often sick and other complications can happen either from their disease. And sometimes, unfortunately, patients who are in the process of waiting for their CAR T cells to be manufactured, they can unfortunately have their disease progress or get too sick to actually receive their auto CAR T cells.
So we remove that barrier with the allogeneic approach. Next slide. So here is just a summary of the phase Ib data in patients with primarily DLBCL, an aggressive form of lymphoma in patients who had received autologous CAR T cell products before. And just to remind people, so this was 16 patients we treated with our optimized lymphodepletion or chemotherapy regimen, which is given before the CAR T cells, followed by low doses of interleukin-2 afterwards. And we've seen in these patients 13 responders, which corresponds to an 81% overall response rate, with some of these responses being quite durable, approaching or I guess over a year and a half now. And we have received FDA Fast Track designation in DLBCL as a recognition of Azer-cel's potential promise.
In terms of the safety, the two key adverse events that are closely monitored in patients who receive any type of CAR T cell product are cytokine release syndrome or CRS or ICANS, which is a neurotoxicity syndrome from the CAR T cells. We'll get into the numbers later, but patients were even patients who did develop these; these were well tolerated, manageable, and all resolved. Next slide. So here's just a, I think, a very nice graphical representation of the responses we can see. So you can see patients in green have achieved a complete response, meaning there's no evidence of disease left in their body. And you can see in yellow the patients who had a partial response, meaning they've had a significant decrease in their disease, but it hasn't disappeared completely.
Patients with stable disease, meaning no change from before they received Azer-cel and one patient who had progressive disease after receiving Azer-cel. And as you can see, some of the patients are still quite early in their treatment course, and we're continuing to follow them. But as you notice on the left-hand side, we have several patients now who are out five or six months or more, with the two longest patients in a complete response for over a year. So this is really encouraging and shows that Azer-cel not only can generate response to these patients, but more meaningfully that these responses can be long-lived. Next slide. In terms of a comparison here, we can see the 81% overall response rate for Azer-cel. And on the right-hand side, you see the three approved autologous CAR T cell products.
And this is in patients who've received at least two prior treatments for their lymphoma. And you can see that we are tracking slightly better than that. And of note, all of our patients have received one of these three autologous CAR T cell products. So it is still pretty remarkable that we're seeing this level of response in patients who had already received an autologous CAR T cell product. Next slide. Here's just a summary of the safety data. So you can see the cytokine release syndrome. About 60% of patients experienced this, but mostly very low grade, one or two. And again, all cases resolved with appropriate management. In terms of the ICANS neurotoxicity, we've only had two patients. One was a moderate grade, one was a higher grade, but again responded to the appropriate treatment and resolved, and all these patients recovered.
The complications for infection, again, are seen in about a third of patients and are of moderate grade, and all of these infections have resolved. Next slide. Here is just showing, highlighting that one patient who has been in CR for over a year and a half now. And you can see on the left that black mass in the orange circle is their tumor. You can see it's quite a bulky tumor in their neck. And this is a young woman who was diagnosed with aggressive lymphoma in 2022. She received four prior treatments for her lymphoma, including an autologous CAR T cell product, in this case, Yescarta, and had a very relatively short response to her autologous CAR T cell product. And then the patient came on study, received Azer-cel, and as you can see, remains tumor-free to this day. Next slide. So here's our proposed.
Clinical pathway for advancing Azer-cel. As you can see, in sort of that second to the left-hand box, we are currently in the phase Ib expansion portion where we're treating patients who've had a prior autologous CAR T cell product, and recently, we started treating patients who have never received a CAR T cell product. Given the exciting data and response we've seen in the later line patients, we felt that this was the right time to see how Azer-cel can perform in patients who've never received a CAR T cell.
The patients in what we call the CAR T naive cohort are made up of multiple different types of lymphomas, including DLBCL, but as well as other types of lymphomas where CAR T cell is not approved, and then, in a few weeks, we hope to meet with the FDA to have our Type C meeting to discuss the current Azer-cel data and our proposal for moving Azer-cel into a potential registrational study. Next slide. Just recently, we announced some of the data in this CAR T naive cohort, so again, these are patients who have never received an autologous CAR T cell therapy. However, they still remain quite heavily pretreated, and of the six patients who've had their first response, we only have data from the first five.
You can see five of those six have responded with three CRs, so we think this is still quite encouraging, and this is exactly what we hope to see with Azer-cel in the CAR T naive cohort. Again, there are many different indications that we're enrolling, which I think gives us additional flexibility in terms of how we can bring Azer-cel to as many patients as possible. Next slide. That's it. Thank you, everyone.
Thank you, John. That was great. I think I'm going to go ahead and open the floor up for any questions.
No problem. Thanks, Leslie. Just as a reminder to everyone, if you do have a question you'd like to submit, please feel free to type it in within Zoom, and we'll get to those now. The first question I have is, how many of the complete response patients were initially categorized as partial responses, and what was the timeline from partial response to complete response?
Yeah. So about a quarter to a third of the patients had a partial response at their first disease assessment, which is four weeks after they received the Azer-cel infusion. And then of those patients who then developed a complete response, it took about an additional two to three months afterwards.
Thank you. And then in terms of Azer-cel's durability, are all patients who had a complete response still ongoing or have some relapsed?
Some have relapsed, unfortunately.
Thank you. The next question I have is, the 4C last week indicated that CF33 and oncolytics are being deprioritized. What does that mean for the company going forward?
Look, I'll take that one. The company had to make an unfortunate decision to deprioritize those. And what that means exactly is that we will look to continue to develop those programs, but in a joint effort, in a collaborative effort, or outlicensing.
Thank you. The next question is, can you put into context the significance of Azer-cel being selected for an oral presentation at ASH?
Sure. The American Society of Hematology, or the ASH meeting, is the largest hematology conference in the world and is the preeminent hematology conference. To put that into context, there will be about 30,000-35,000 people who are going to gather in Orlando to hear the latest data. The fact that Azer-cel was selected as an oral presentation at the podium is highly significant. It is extremely difficult to be selected. This is peer-reviewed by experts in the field, and we feel honored that they felt that the data that we submitted in our abstract was interesting and important enough to deserve an oral presentation. We are very excited about that.
Thank you. The next question is, if the FDA agrees to a registrational trial, when would that likely start?
Well, I think we won't really know until we get the feedback. There are a lot of pieces that will go into that.
No problem. Next question is, how do you think Azer-cel will fare in relapsed refractory DLBCL as a market? And this is citing Allogene's Semacel product, which is in a phase II.
So Allogene's product is in a very different space. I mean, they're taking a very unique approach to how to bring Semacel to patients. I think in terms of the market, I mean, the market is fairly large. It all depends on your data, right? That's going to determine market uptake. And then you have to then deal with reimbursement. I think if we can continue on the track with our current pace of response and durability, I think we have a good shot. Again, I think trying to predict market uptake from phase Ib expansion is pretty difficult.
Thank you. The next question is, can you advise on the IP protection strategy for the use of IL-2 with CAR T therapy?
Yes. So we are working with our IP attorneys on that currently.
The next question for you, Leslie, is, what's the partnering strategy for Azer-cel? and when do you expect to have any updates on that?
We wouldn't announce on any partnering until after it's completed. I am hopeful, and we are speaking with as many partners as we can. ASH is a great conference to be able to speak with partners and to present our data to. I think it's promising.
Thank you. The next question is, what's the plan for imaging with Azer-cel and expanding across numerous indications as you've been announcing recently?
So the rationale behind that, again, is to try and bring Azer-cel, the benefit of Azer-cel to as many patients as possible. So this gives us additional flexibility in our clinical development strategy.
Thank you.
It opens up various different avenues in order to register or to have a pivotal study. These niche indications tend to be so niche so that the FDA gives you a green light on a single arm, which we like very much. So it's great that the Azer-cel is performing well in this space, enough for us to pursue potentially one of these indications as a pivotal study.
Thank you. What is the average durability of CAR Ts currently being used? I assume that's a general question, not confined to Imugene.
Yeah. So I mean, it depends how you define that. So with current autologous CAR T cell products, about 30% of patients will have a durable response, meaning one to two years. Everyone else, unfortunately, will have a relapse.
The next question is: precision head stealth cell under trial, has Azer-cel been modified by Imugene to enhance its performance in any way?
No, it has not.
Thank you. The next question is, across how many different cohorts and under which indications will patients be enrolled for the Azer-cel trial?
So again, there are currently two cohorts open, patients who've had prior autologous CAR T cells, and then the other cohort is patients who have not had prior autologous CAR T cells. In the auto CAR T relapse cohort, that's primarily patients with DLBCL or a variation of DLBCL. In the CAR T naive cohort, meaning patients who've never received auto CAR T. I believe there are six potential indications that are available for patients, ranging from DLBCL to follicular to rare lymphoma subtypes such as primary CNS lymphoma or marginal zone lymphoma.
Thank you. And a couple of people have asked, despite the CF33 programs being deprioritized, is there still a plan to combine Azer-cel with oncolytics?
That's not our immediate plan because Azer-cel obviously is performing well enough to be able to discuss with the FDA regarding our pivotal study strategy, and so perhaps in the future, but it's always nice to be able to combine an investigational product with an approved product because you don't then have to go through two investigational products going through a pivotal design. Meaning it's always good to hitch your asset with an approved product as a combination, so I think we will be seeking those opportunities more than our internal as a priority rather than combine with Azer-cel.
Thank you. And just looking ahead, someone's asked, when do you expect the scan data from that sixth CAR T naive patient to be released and future patients as well?
Look, we'd like to have a bolus. I know John and I like to have a bolus of patients in order to have a readout. These cohorts take time and effort to put together. And so that, but fortunately, that cohort of CAR T naive patients is enrolling at an extremely accelerated rate. I think the investigators are voting with their feet and putting their patients into our Azer-cel study. So we hope to update the market quite soon.
Thank you, and Leslie, someone's just asked with regards to cash on hand currently and the expectations there going forward in terms of cash burn.
Look, it is as the guidance that we provided before. And so we have a cash runway. And just to thwart any questions about capital raise, we would never announce on a capital raise before. We always announce after it's completed. But it's the same guidance as we've given before, which is cash out to June.
Thank you. And then another question that's coming is, will you be able to announce the requirements and criteria set by the FDA once you've had that meeting?
We would be obligated to provide any update that we receive from the FDA because as it would be material.
Great. Well, that's all the questions, Leslie. I'll just throw it back to you to provide a concluding comment.
Look, thank you so much for joining us today. I want to thank my Chief Medical Officer, John Byon, who is doing a phenomenal job. I just want everyone to be aware that the brilliance of him is the reason why we have put IL-2 together with Azer-cel, which is just performing just beautifully, and so I want to thank everyone. Look out for the FDA feedback announcement as well as future CAR T naive announcements as well, and then the ASH conference, but that's it from me. Thank you so much for attending.
Thanks, Leslie. Thanks, John, and to everyone for joining today.
All right. Thank you, Matt. Thank you, everyone.