Thank you for standing by. Welcome to the Imugene Investor Webinar, with today's presentation focused on last week's announcement that the company has acquired a license to the azer-cel technology from Precision, Precision Bio. Joining us from Imugene today, we have the CEO and Managing Director, Leslie Chong, as well as the newly appointed COO, Dr. Bradley Glover. All participants are in a listen-only mode. There will be an initial slide presentation that will last for approximately 20 minutes. We'll take questions thereafter. If you'd like to submit a live question, please do so using the Q&A panel within Zoom. Just noting we've received a lot on email already. We'll get through as many as possible. To kick it off, I'll hand it over to Imugene CEO and Managing Director, Leslie Chong. Please go ahead.
Thank you, Matt. Before we start the presentation, I just wanted to address a few key questions up front, and mainly, I want to be absolutely clear that Imugene is not changing strategic directions. With the acquisition of azer-cel, it actually improves the strategic directions and our goals. Our strategy and goals have always been that either the company gets acquired, we partner with Big Pharma for development, et cetera, or, or we out-license each of our technologies separately or develop or commercialize our assets. With the acquisition of azer-cel, it actually accelerates all of those. Imugene is already involved with cellular therapy in some ways, due to our combination with CD19, expressing onCARlytics, so it adds value to the existing pipeline. Some of you have asked, why are we raising money?
Especially the $35 million last week. We have previously said our cash runway was strong, and it is strong, but that was before we saw this amazing opportunity with azer-cel. When that appeared, the strategy of our-- and our cash position was readdressed, and the board took the view that we did not want to eat into our existing cash for our other programs, such as our promising onCARlytics. We decided to top, top it up now. Also the question of dilution. Imugene is roughly around $500 million market cap, and $35 million is only a dilution of roughly about 7%, which is, which we do not view as material.
We know that shareholders like to be included on the same or better terms than institutions, so we have included an SPP, so that the cap-raising process is democratic and all shareholders, and you can participate. Lastly, why did Chimeric get paid the AUD 3.3 million finder's fee? The azer-cel technology was sourced from CHM. The two CEOs of Precision and CHM are close friends, but unfortunately, due to the cash position, it was clear that IMU was in the better position to deliver on the promise of azer-cel. Imugene had the opportunity to license the technology from Precision, and as a result, we had an obligation to pay CHM the fee. Paul Hopper was conflicted, so he was excluded or recused from any decision-making on the asset and had no involvement in the decision.
Okay, I am going to go right into our presentation. Brad, which view am I on?
That's great, Leslie.
Okay, great. Thank you. It is my true delight to introduce you to Dr. Bradley Glover. He's had roles at Kite Pharma, Genentech, Roche, Illumina, and all in a very senior position of exactly this, CAR T and Allo CAR T positions. He's got corporate development and technical operations that he's experienced, that he's been awesome, bringing in all our CMC and tech and strategic operations in Durham, North Carolina. Brad will be providing some of the presentations today, so you get a flavor of his knowledge, but welcome, Brad.
Thank you very much, Leslie. I'm excited to join the company and look forward to being part of the journey together.
Imugene currently has six unique assets, four platform technologies, with a myriad of solid tumors that we're addressing, and now we get to add blood cancers to our mix of clinical studies. We already have two existing supply agreements from a major pharmaceutical company, four beautiful, unique asset, and the one that I'm talk, we'll talk about today is azer-cel and how it marries quite well with our existing pipeline onCARlytics. Just a brief overview of the landscape of autologous CAR T. Autologous CAR T came in quick and swift in 2017, and all of these are approved, and several targeting CD19. That DLBCL space is where I want you to focus on later. Giving such response rates as anywhere between 53%-98% overall response rate.
Unfortunately, we do not see these these response rates in solid tumors, and that's where onCARlytics come in. Beautiful response rates, autologous are the only one that's approved. Our CAR T that we have just licensed is what's called an allogeneic, so I'll call it allo from allo CAR T from here on in, and it's called azer-cel, and we've licensed in this from Nasdaq-listed company called Precision BioSciences. With that license, what we get is first-in-class, first-in-class allo CAR T that has the potential to be marketed. First allo CAR T marketed in the world, and it will be from Imugene, which I am completely over the moon about, and this could happen in a matter of few years. We have robust data from 84 patients, and we've completed drug materials.
We've also taken in the manufacturing facility, along with all the technical and technical and scientific experts in the Durham, North Carolina site, that Brad will talk about in just a second. Just to give you an overview of what's the difference between autologous or auto CAR T versus allo CAR T. Auto CAR Ts are highly personalized. They're dependent on the patient's own T cells that you reprogram, re-engineer, and inject it back into them, and then your CAR T cells go after the certain kind of cancer cell. Those are the ones that I just showed you for the approvals. Allogeneic CAR Ts are what's called off-the-shelf and on-demand. These azer-cel specifically is taking healthy donor cells. They're re-engineered by a gene-editing platform called ARCUS. There is that beautiful universal match with azer-cel that we have seen across 84 patients.
It's called off-the-shelf. The batches can be frozen and shipped to a myriad of clinics and hospitals, and then those batches provide multiple dosing, not just a single patient. The process, we would argue, if not better than auto CAR T, that these souped-up or supercharged CAR T cells go after your certain kinds of cancer. I'm going to let Brad explain. Given his wealth of experience in AlloCAR Ts and auto CAR Ts, I'm going to have him explain the main differences.
Yeah, I appreciate that, Leslie. I mean, this is a fantastic opportunity. You know why I think the industry has seen a lot of success with the autologous programs in some of the slides previously that Leslie covered? There are really some challenges there that I think the industry's gonna have to address. Allogeneic therapies really does that. You can start to really drive down some of the manufacturing costs. The COGS are gonna be very important to have these lean. Throughput's important, making sure you drive out variability in the process that can be associated with patient starting material, as well as the variability and potency that you can see.
The, the unique process that azer-cel has associated with it, that now Imugene has, really is gonna position the company to be able to make all-allogeneic therapies, against multiple indications and really, have an efficient, cost-effective process, to be competitive in the landscape and ultimately, make a difference in the lives of patients. That's our hope.
Thank you, Brad. auto and allo, one of the things that's starkly different to me is autologous CAR Ts are so patient-dependent. It is something like 19 days to about 42 days before a patient can get their own injected T cells or souped-up T cells. During that time, a lot of the patients progress, so they have to get bridging therapy. There is a process, a leukapheresis, where they sit in a chair for 5 to 7 hours to get their white blood cells so that they can tease out the T cells, and that could be processed. With allogeneic, the promise is here, it's on demand. When the patient is diagnosed, they could sit and get their drug as needed. The first indication of choice is, I think it's such a clever design.
There is DLBCL happens to be a pretty deadly and aggressive type of non-Hodgkin lymphoma. Roughly 80,000 patients, just U.S. alone, are diagnosed with non-Hodgkin lymphoma, and 30% of those cases progress into this aggressive type of non-Hodgkin lymphoma, and it's called diffuse large B-cell lymphoma. This DLBCL patient population have really limited options, and it's a high-grade, fast-growing cancer type. If you're diagnosed with DLBCL, you might be given weeks, if not a few months, to live. We think that this is a, a huge patient population that we can serve with our first AlloCAR T approval. Currently, the DLBCL patients are treated with R-CHOP. This is a pretty rancid combination of chemo and steroids, and roughly about 60% of the patients are cured with this.
However, if they progress or fall, you know, fall on those diseases, then therapies, then what they have choice of is a high-dose chemotherapy again and maybe a stem cell transplant. That gives you roughly about 20-25% response rate. The new sort of process is for all those approved auto CD19 CAR Ts to be treated in the second-line space. As Yescarta, Kymriah, and Breyanzi move into that second line, there leaves a 60-65% failure rate, and that's the third-line space that no one has. This is the space we're gonna go into for our fast to market strategy. This is our registrational strategy, and I think this is why I'm so excited. The past data clearly indicated that we were incredibly well in this space, and I'll tell you why.
84 patients were treated with azer-cel. 61 were non-Hodgkin lymphoma, 23 were in leukemia state. We saw a fair amount of significant responses in both, but out of that 61 non-Hodgkin lymphoma patients, 18 patients had a CAR T relapse. They took auto CAR T, relapsed, and out of that 18 patients, 14 were DLBCL. That exact population we're going into for that registration, a whopping 83% overall response rate, with 61% co-confirmed response rate. Beautiful! More than half had a durability or long-lasting response for 6 months or greater. We know for a fact that CD19 as a marker, still is relevant even after you fail on therapy. 85% still maintain a CD19 target, and Yescarta and Breyanzi and Kymriah work well enough.
However, 60%-65% of the patient population fail, progress off of this disease. This is the line that we're going into. 30,000 patients with DLBCL are diagnosed just in the U.S. alone, 33% relapse off of chemo. They go on auto CAR T. That 60%-65% of the population is what we're focused on. The approved auto CAR T, the median price is roughly $375,000. If you look at the total addressable market in this space alone, and U.S. sales at auto peak sales, you're talking about $2.5 billion. Once we go into the clinic in DLBCL, we'll look for other indications as well as such as pediatric ALL.
The space is only growing, even in the third line, 5,700, 5,700 patients in the U.S., 5,300 in, in the Western Europe. As the sales of autologous CAR T grows, we're looking at just in 2018, it was a $292 million in sales. 2022, it became a blockbuster with $1.8 billion in sales. They're projecting just in 2023 alone, that $2.2 billion, it's only growing. Again, 60%-70% of the patient population progress off of this therapy. They have no other lines of therapy to go on. It will make it easy to enroll, as well as, hopefully, registration study to market. Excitement here. We already have five of the major cancer centers in the U.S. already signed up for our registrational study.
This is registrational to market. Just wanna be clear. There are currently-- these five sites are already participating in our phase I-B study. We've already received FDA feedback and guidelines regarding this pivotal registrational to market study. Drug material, which is one of the most difficult part of any CAR T development, we've already got the manufacturing all locked down, and I'm gonna have Brad talk to you about our beautiful facility in Durham, North Carolina.
Absolutely. You know, they say in, in, in cell therapy, the process is the product, and that is really so true. I was just so excited when we had a small team go out to North Carolina this past week and to meet the new Imugene employees as well as tour the facility. Just really remarkable facility and incredible dedicated workforce out there. Not only the facility for the manufacturing, we have additional space with process development labs. You really have that CMC continuum, hand off from research to process development to the manufacturing facility. It's a beautiful continuum there. The MCAT facility, as we call it, is about 32,800 sq ft.
It's got manufacturing space and a really flexible expansion space that we could go into, and that keeps our strategic options open in the future. With a GMP compliant, as well as, this facility has gone through several third-party audits and really had no findings. It's, it's really operating effectively and in a compliant way. It's really a turnkey solution for final drug product supply, It's been proven. It's, it's not an unknown entity. It's been proven. It's manufacturing product right now in patients, We expect to really transition this into the future. It's got expandability, it actually has made product, We have process improvements that we're already have in our, in our, project portfolio, to increase throughput and drive down costs.
It's a, a remarkable asset the team has acquired, and the employees are super dedicated, super talented, and it's just a lot of energy around this deal.
Thank you, Brad. He spent all of last week there, welcoming our product. Another exciting aspect of azer-cel is that our onCARlytics, it was right for it. It's our onCARlytics, again, for those of you who are new, is an oncolytic virus that expresses or upregulates or flags a solid tumor with CD19. That combination is just a match made in heaven. We now not only have a footprint in solid tumors, we now have a huge footprint in blood cancers.... The timelines will come in fast and swift, as early as in the next few weeks or maybe upwards of a month. We'll have the FDA drug lot release. For every lot that you use for any clinical trial, the FDA has to validate it, and that is already with the FDA being reviewed.
That is the drug lot that will be used to validate our registrational study, so that phase II registrational to market study. You will get updates throughout, and we're going to enroll specific patients that is going to be in the registrational study, that DLBCL population that have failed off of previous lines of autologous CAR T. Specifically, those patients. We've got two reasons why we're going to win in the registrational space in that study. Multiple goals, multiple value realization. We've expedited this. I think we've actually, you know, just put it on a fast speed, company acquisition, partnering with Big Pharma, licensing technology separately, and also the commercialization independently, and that could come as early as in a few years. I am... I think I'm, I think I'm done.
All right. Thank you, Leslie. We'll now jump into the Q&A session. If, again, once again, if anyone would like to submit a question, please do so using the Q&A panel within Zoom. I'll start with some via, that have come through via email. How will Imugene utilize the manufacturing facility it has acquired in North Carolina?
I think exactly what Brad says. It's currently had made the drug for the 84 patients, previously on the study and will be producing more of our batches moving forward for our registrational study.
Very good. The next question is: Has, has the bought license finally rounded up the required technology base for all CF33 variants, or does Imugene need more?
I think you're talking about the CF, CF33 onCARlytics and its expression of CD19. The more we have partners or combined with the CD19, be it allogeneic, be it auto, be it bispecific, be it monoclonal antibody, it actually increases the value of onCARlytics because we're sort of the facilitator. If we can combine with any CD19s out there, it makes us even more attractive, I would say.
Thank you. The next question is: What is the long-term strategy? Is it still selling after phase II/regulatory approval or now going the way of commercialization by itself?
I mean, all of it. Our four goals are quite simple, that I just explained. This acquisition accelerates all four.
Thank you. The next question is. Excuse me. Leslie has previously referred to Imugene 2.0. Can you please elaborate on that, and was this acquisition part of it?
I think, I'm not sure. I always sort of talk about Imugene always in a start-up being very fast and efficient, and we're sort of scrappy, azer-cel makes us a little bit more rounded, I would say. We need to be a little bit more... We've got more people on board. We have to be a little bit more like a, a real biotech in this world. It makes us much more visible to the U.S. biotech as well. It feels like 2.0, but it's business as usual for me.
Next question is: Are royalties tied to US dollar sales or sales volume?
Those royalty milestones that we spoke about are all inclusive of US sales, EU sales, even when we go into new indication. The cells are upwards of billions and billions, that's all inclusive of everything.
I know you touched on this one, what is the estimated timeframe on the new Imugene azer-cel product? When will it be ready for use for as medicine for patients if the balance of the trials are successful?
I think in a few years, because we will likely go for, of course, with FDA guidance, for accelerated approval. That means as early as when we can get progression-free survival, when we hit those markers, we can actually start filing for a marketable process, which is called a BLA. That could happen in a matter of few years.
Thank you. The next question is: Can you please explain how this acquisition is not buying a competing product? azer-cel looks very similar and is further advanced than the Imugene product.
I'm a little bit confused by that because we have four platforms, and they're all quite different. They're under the umbrella of immuno-oncology therapy, we have the B-cell immunotherapy, which is a cancer vaccine. We have CF33, which is an oncolytic virus. We have onCARlytics, which is an oncolytic virus that expresses CD19 or enables CD19 in combination with the CD19 therapeutics. They're very different lines of indication, and we don't have a CAR T in our product until, you know, just a few weeks ago. No, I don't think that they're competing at all. They're actually pretty complementary.
Thank you. The next question is around Precision BioSciences. Most recent earnings update said there were several interested parties in azer-cel. Does that mean there was a competitive bidding process and thus a higher price had to be paid?
We didn't go into a competitive bidding process because Precision BioSciences loved the fact that Imugene and the people in it are clinical developers. The fact that we have completed a phase II study with positive results in four and a half years is quite attractive. We are all clinical drug developers by choice, and I think they really like that we would take in their product and start developing from day one, and we have done that. We actually paid fairly low prices, given that we know Pfizer and Astellas, two pharmaceutical companies that have paid into a CAR T company, but rights of refusal at $25 million-$50 million. We paid quite a lot less to, to license in the entire oncology platform for use for $8 million upfront. Pretty good.
Leslie, there's been quite a few questions coming just around the manufacturing space. A couple of the common questions are: Can it be used for other viruses or drugs in the portfolio? Another question was: Is it producing revenue at all?
Sure. Right now, we're Brad and I are just focused on getting our, our registrational study started. All the manufacturing, sweat, tears, you know, are gonna go into producing enough batches and drug for our registrational study. We will look into other aspects at a later time.
You know, and Leslie, just to add on to that, I think that's, that's spot on. The, the types of facilities used in allogeneic and even autologous cell therapy, by definition, have flexibility built into their layout as well as their automation and desktop equipment. In the future, you will have that strategic option if the, the team so desires to move that direction. For now, it's all hands on deck. Let's get azer-cel progressed, and I would say there's just an incredible amount of organizational focus on that right now.
that's a good segue into this question, which is, can you please elaborate on what a registrational to market study is, and when can you actually charge patients for the therapy?
CAR T therapies, normal state of development is you go into phase I, dose-finding, you go into phase II, proof of concept. Phase III is where, that's the registrational study. That's once you completed that, you get to market your product. With CAR Ts in particular, because of the whopping response rates and the unmet need out there, it is highly accelerated that where you can go from phase I, and most of the CAR Ts have been approved at phase II. When I say registrational, that is the last phase of a study before you can market.
What I'm saying to you is, azer-cel has the capability because we have chosen the right indication of a truly unmet need, that we think there is nothing else therefore, that we can walk through the FDA process much faster and hopefully better, given our data package, to get this marketed. Registrational study just means a study before you market, market, and that this could happen in a matter of few years.
The next question is, what does this mean for the existing trials with onCARlytics and other partners?
Nothing. Our pre-clinical, non-exclusive combination therapy that we have with AlloCAR Ts and autologous CAR Ts, bispecifics, and iNKTs are all ongoing. What we are currently doing is, onCARlytics is going into the clinic with a bispecific co-product called Blincyto in combination. We will look at preclinical with, with our azer-cel because it's ours, and we have a lot more control over it. There's nothing that precludes us from continuing on the non-clinical work.
The next question is, how are the T cells sourced to manufacture for azer-cel? Is this a possible limiting factor for expansion?
No. Healthy donors provide that. They go through a pretty rigorous screening process, but the leukapheresis, or the blood samples, come from a myriad of different donors, and they're all healthy, so they're programmed, and then they're gene-edited to perfection and really souped up. We actually have donors throughout the process and We even have enough for the registrational study or that to market or the phase III or whatever you wanna call it.
The next question is just around competitive landscape. If there's anything else targeting similar indications to azer-cel?
There are, and that's the beauty part. When we look at the landscape, and I, and I'm gonna bring this to, to, to the wider market, that there are competitions. However, this is such a clever design. There's companies called Allogene as well as Adicet Bio that are in this space, but they're not going after the auto CAR T failures, which I showed you is a growing population. They're going after auto CAR T naive, and they'll soon go into the space, but I think we're ahead, and we just need to keep going and get us into the clinic and get us the registration and put our flag to say we've got the official win and FDA approval for this drug before. I think this is the first-in-class allo CAR T out there.
Another one I think you've touched on, but when will any studies based on synergies between azer-cel and oncolytics start, for example, preclinical testing?
We want to have enough batches and drug for the phase I-B. That is critical. That's our, as, as Brad said, that's our organizational goal, to get that enough batches for the registrational to market, the phase II, III that we're going into. Outside of that, anything remaining, yes, that's our next second priority to combine with our onCARlytics. I would say our first priority, to use the drug for the in-clinic for the patients.
You've previously mentioned that the plan is for Imugene to be bought out by Big Pharma. Has this strategy now deviated, given to Imugene being competitive in the market?
No. I think it actually accelerated. You know, I can't, I can't impress upon folks enough that our goals of either being bought out, partnering, commercializing or out-licensing ourselves, all have actually come to a closer finish with azer-cel acquisition.
Great. Thanks, Leslie. There's been a large number of questions come in, we'll endeavor to come back on any others on email separately. In wrapping up, another common question we've received has been around the SPP participation and documentation that goes with that. The timeline for that can be viewed on page five of the ASX announcement regarding the capital raise that was lodged on the 18th of August. The prospectus for the SPP, though, will be dispatched on Monday, the 28th of August, with the SPP closing on the 14th of September. Just wanted to clarify that for quite a few people asking. Leslie, I'll just hand it back to you if you had a closing comment before we wrap up.
Well, I'm thrilled that Dr. Bradley Glover has accepted the appointment, and I am even more thrilled that we're gonna take azer-cel into the clinic and hopefully be the first AlloCAR T to be approved in the world out of Imugene. I'm quite proud of everything that's happening right now. Brad, do you want to say a few words?
No, I just thank you so much for inviting me on this journey with the incredible employees at Imugene. I mean, without people, you, you don't get anything done, and they're very talented, very engaged, and I, I think that the organization has really put itself in a position to make a difference for patients. Thank you very much.
Great. Thanks, Leslie and Bradley, and thanks to everyone for joining today.