Good morning, everyone. Thanks for joining us for another session at the 44th Annual JP Morgan Healthcare Conference. I'm Brian Cheng. I'm one of the senior biotech analysts here at the firm. I'm also joined by my associate, Sean Kim and Maren Waggie, who are also in the audience. On stage, we have Precigen. I will now pass the mic to their CEO, Helen, for a short presentation, followed by a live audience Q&A. Helen, the stage is yours.
Thank you very much, Brian, and thank you for having us at the conference. It's great to be here today and presenting on behalf of the Precigen team. Let's get into the bulk of our presentation, and we look forward to also the discussions afterwards. I will be making some forward-looking statements, so please make sure that you read the SEC-required slide. With that in mind, I think this slide, I just want to point out to a seasoned leadership of the Precigen, which for the past four years have advanced a very, very exciting portfolio forward that I will be talking about, and one of our major assets, PRGN-2012, which in a matter of three years have been advanced to the rapid accelerated path, and we just submitted BLA.
With that in mind, let's go through what we have really accomplished and what we are talking in regard to the Precigen and how Precigen has been advancing in the past year, especially from last year at JP Morgan. We currently have really de-risked the highest priority asset, PRGN-2012, which will be, if approved, the first therapy for recurrent respiratory papillomatosis. And the pipeline is as a result of a very differentiated gene therapy platform of the Gorilla AdenoVerse platforms, which I will be speaking about. Mainly, this platform is really applicable to all gene therapies, but specifically, we have focused on HPV-related rare diseases such as RRP or in cancer diseases. We also have built the capacity and the manufacturing facility, both GMP and now cGMP, for a scale-up for commercial manufacturing if drug approved.
Also, at the very end, I will be discussing our revolutionary, truly paradigm-changing UltraCAR-T, which is the only autologous overnight CAR-T that does not require a viral vector platform, and it can be done at the hospitals with a much lower cost assumed and very rapid, basically, manufacturing. We showed the safety and efficacy, which I will be discussing. Finally, as we have communicated lately, we have now starting January with approximately $100 million at hand, which we believe it puts us well after, hopefully, the approval of the PRGN-2012 and to commercialization well into 2026. With that in mind, let's just start with the platform that PRGN-2012 is based on. This is our proprietary Gorilla Adenovector platform, which is unlike any other adenoviral platforms that it's known, including the chimpanzees. Why do I say that? It's very simple.
These Gorilla Adenovectors, which transfers the genes or the epitopes of an interest, they basically have a very large capacity compared to other Ad5s that are at best around five. You're looking at 12 kb. So you can put much more genes and epitopes in them. But more importantly from that is that you can repeat those. Why can you do that and you cannot do that with other adenovirus? It's because the individuals, humans, don't have either any preimmunity or seropositivity or very little. So you can repeat dosing this and, as a result, generate a very, very high specific CD8 responses. We have shown that in our clinical trial, and I will show some of the data today as well. We have repeat dosed this number of times, not four times, but sometimes up to 16 times in some of our other trials.
We have seen a key enhancement of the T cell responses. Finally, we do have the highly productive manufacturing cell line, which is, again, we have a full IP around that and our own GMP facilities that it produces the material and allows us to very rapidly move. On the left-hand side, you see the portfolio that we have built based on our Gorilla Adenovector platforms. Of course, our lead asset is PRGN-2012 in RRP, which I will go through more comprehensively. We also have built the PRGN-2009, which addresses the HPV-related cancers, both in head and neck cancer, cervical cancers, which is in a phase II clinical trials currently. We have reported data on that at ASCO in the checkpoint inhibitor failure patients. We were able to show 30% objective responses in this patient population, which is quite significant.
We are very excited about that. Let's go to PRGN-2012 and the treatment for recurrent respiratory papillomatosis. This slide, I think it really points out what a devastating disease this is. Recurrent, as the name is obvious, it's recurring benign tumors in these patients that they can be infected with HPV 6 or 11 from childhood as they pass through the birth canal or in the adult through a sexual transmission. Now, the root cause of this disease is an infection of HPV 6 and 11 and leads to recurrent benign tumors developing in trachea and on vocal cords. There is no current approved therapy for this patient. These patients were diagnosed some more than half a century ago. So this disease has been there for a long time. It's not the lack of, basically, investigators trying to come up with the treatment.
None of the treatments have worked. And can you imagine, for a patient, in order to be able to breathe or speak, they have to go to recurrent surgeries. And some of our patients, and I showed that, per month, they had required a surgery in order to be just functional or can breathe. So you can imagine what a devastating disease it is. It's a rare disease with unmet needs. And as I mentioned, surgery is not curative here. It's just, basically, it removes the tumor and the tumor comes back again and again. Unlike other surgeries that usually surgeons are very successful by removing various tissues, this is not the case here. So I want you to keep that in mind. And this is the progression of our program at Precigen that we started the discovery in 2020 in the midst of, actually, COVID.
In 2021, we had started our IND in March, April of 2021. By December of 2021, we finished phase I, and we had the data on safety as well as the dose and expanded to 12 patients at dose level two. As you see, in January of 2022, we started a single arm phase II, very similar design, exactly the same design. In 2023, based on the data from our phase I, the FDA actually awarded us the breakthrough designation and received the FDA accelerated approval pathway, which was very exciting because this is the first drug product that received that from the FDA. In 2024, we reported at ASCO at the breakthrough, basically, presentation, the data from a pivotal phase I and phase II single arms, positive, significant data that met all the endpoints.
Currently, as we already have communicated, by the end of December of 2024, we submitted our and finished submission of the rolling BLA. We are very excited and hoping to receive the approval by second half of 2025. With that in mind, what have we? If we look at the pivotal data, our pivotal data, as was presented in a late-breaking presentation at ASCO, showed significant efficacy with very, very favorable safety, which I will take you through that. As I mentioned, we have submitted the BLA. Now our commercial organization has been put together under the leadership of Phil Tennant, which today I will have on the stage with me, and really preparing for the launch in the second half of 2025 if drug is approved. We are looking forward to that.
And finally, the cGMP and under the leadership of our manufacturing head, Dr. Bottmann, and Dr. Shah, the chief operating officers, that it has moved from the perspective of being just a GMP facility now to the cGMP facility that, if approved, it has all the ability to scale up on a drug substance level and have done so for the commercial path. So a little bit about the mechanism of action of our gene therapy drug, PRGN-2012. This is basically a drug product that you inject subcutaneously. It does not require any kind of a device or anything else. It's very easy to administer. And upon administration, it basically you are training the T cells of the patient to basically train to see the HPV 6 and 11 infected cell, which is the root cause of this disease, and destroy them.
And that's what you're basically building an internal army to go around in a systemic fashion and anywhere that they see these infected cells that leads to the benign tumor, destroying them. The clinical trial that we started, both on phase I and phase II, and the design has been exactly the same thing. It's basically the patient we brought in, the most severe patient population, which was defined as having at least three surgeries in a prior year, prior 12 months. They came in, and because they needed a surgery for either being able to breathe or speak, they did the debulking, and then they received four injections. This is a course of PRGN-2012, four injections over approximately three months. And then they were followed by their own physicians and centers of excellence for a minimum of 12 months.
Of course, we have been following them even for much longer. It's quite interesting data on their durability. On the right-hand side, what you see is basically the patient population characteristics. I'm not going to go through all of that except saying the patients that obviously we have been treating, they have been adult patients. You can see that more than a third of these patients, they had the disease from childhood. Can you imagine some of these patients from the age of one? They have been requiring surgery, some of them, on a monthly basis even, just to be able to breathe and what they have gone through. Safety, I think this data were presented at ASCO, very simple.
There is really very, very favorable safety, grade one, grade two, which is basically the rash at the site of injection, maybe a little bit of fever, and by next day, usually it resolves, and this is extremely important because the patients, it's very easy. The physicians, they describe this as getting a flu shot. That's how they look at it. Now, the data. This is a combined data patient by patient, and this is what it was presented at ASCO. As I mentioned, the FDA had agreed that the single arm phase I, 12 patients, plus the single arm phase II, 23 patients can serve as a pivotal, and we didn't need to do a phase III or placebo control trial. Based on that, gray bars is showing you all the patients 12 months prior to joining the treatment and the number of surgeries that they require.
You can see on the top part of the graph, some of these patients, they require 10 surgeries, eight surgeries, practically every month requiring a surgery, and then the zeros point out to the 12-month follow-up. Our endpoint was very robust, and it was no surgery to be done, not reducing the number of surgeries, but no requirement at all for surgery, and not only we have met that, but we exceeded the endpoints that we had, and we have been following these patients, and some of the patients from our phase I, they have passed more than 32 months and approximately some of them 36 months now that they have not required any surgery whatsoever.
So this is the first time that any therapeutic, and by that, everything has been tested in these patients, including checkpoint inhibitors, and they have failed, that these patients, they have not required any surgery for very durable timelines. Now, on this slide, what you see is the picture of the vocal cords and trachea of some of these patients prior and after. And of course, we have this for all of the patients. And you can see the clearance of these tumors from the throat or from the vocal cords. And this directly corresponds to the Derkay score, which measures the number of these benign tumors that they now reduced significantly or to none. And also the Voice Quality Index, which is very important when these tumors are developing on the top of a vocal cord.
On the right-hand side, the blue dots that you see, it's from the responder patients. These are the patients that now you can see they have developed a very significant immune response, which goes to the root cause of this disease, which is the clearance of infection in the tissue and not allowing benign tumors to reoccur. As I mentioned, we see PRGN-2012 as the one to have the possibility to be the first and the best in the class, not only based on the safety efficacy data, but the ease of the administration. We have established the mechanism of action and shown that the direct response is related to that. There is a lack of meaningful antibody, neutralizing antibody, which is associated with other adenovirus platforms. The reason for that is these vectors directly push toward the CD8 responses.
They are quite differentiated than others. We have started our confirmatory trials, which is again single arm, 35 patients, exactly the same design. And this has been in agreement with the FDA. And we are currently enrolling in that. And we also, as I mentioned, we are very excited that by the end of 2024, we submitted our BLA. And we are waiting for the BLA review and acceptance and then a PDUFA date that is given. And obviously, we have asked for a rapid review, which it puts it at six months review period. So commercial opportunity later on, Phil, we'll be speaking more to that. But one of the things that always comes out is the prevalence of RRP.
We have done the analysis, and we have shown that the prevalence of RRP is not expected to be impacted by the Gardasil for the span of drug treatments that we have for PRGN-2012. This is based on the very detailed research analysis that we have done, and we can speak to that. One of the other aspects that has been somewhat always different numbers has been put forward over the years. The original studies that they were done in the 1990s and looking at the number of RRP patients, they pointed out somewhere some studies between 14,000-20,000 patients that in the U.S. We have done now a very detailed study that has gone to the electronic patients' data.
And we always, and from what we have heard from our investigators, that the idea was that they were much higher, and this was the 20,000 were underestimation. And our data now shows that actually in the US alone, it's 27,000 patients. And this is with the stringent criteria. And then ex-US, we are speaking about more than 125,000 patients. And with that, this makes basically the value of this drug in a multi-billion-dollar globally. Now, what is very important, and I want to take a few minutes just to speak, it's what does this mean for a patient and what does it mean for the investigators that they have been treating these patients? This is a quote from the president of a patient advocacy group. And I'm just going to read the first part. I think about what it would be like if there is a therapeutic option.
I could go to my laryngologist and get an injection. Even if I had to do that every single month, I would do that a thousand times over rather than having a surgery. Now, imagine that our data on the efficacy side in a span of 90 days, you receive four subcu injections, and we had 51% complete responses in this patient population. On the other hand, a lot of people, they think that surgeons, they really like to do this. But one of the things we should always remember, our surgeons have been trained to go in and eliminate the issue with the surgery. Their purpose is never to go in and keep going back in there. A good surgeon sees themselves by curing whatever the problem is. And unfortunately, in this disease, that is not the case. And this is a quote from one of those surgeons.
Nobody wants to operate on these patients over and over again because that leads to further scarring, complication, and risks, and nobody wants to do that, and you can imagine the patients don't want to go through that, and that's the importance of this drug for this patient population. And with the PRGN-2012 drug product that we have, the profile, the safety, ease of administration, efficacy of 51% response, and having no treatment, of course, you can see the possibility of this drug product for this patient population. cGMP readiness, we have our own cGMP facility. And this is very important because that has allowed us not only to produce the material for our clinical trials, for our confirmatory trials, but also has allowed now for it to be ready for commercialization and scale up at the DS level if drug approved.
Finally, I'm going to take the last few minutes before we go to the question, talk about the other side of Precigen and cell therapy, basically platform that we refer to as UltraCAR-T. Our UltraCAR-T truly is the overnight autologous CAR-T that you can produce, basically take the T cells from the patient overnight and put in a CAR-T plus a switch that in the case that you want to eliminate T cells, you can activate that switch and a membrane-bound IL-15 that continues the manufacturing directly within the body of the patient and allows these cells to persist and grow when they need to. They just survive when there is no antigen around. This process that you see, this happens in the hospital and has been done at Moffitt Cancer Center, Mayo Clinic, Fred Hutch, and also University of Washington.
What you see is the patient's basically T cells, they come in, they're frozen, and when they need, they basically take that. You can now, in a non-viral way, using ultra plasmids, transfect by using the UltraPorator, which we have developed this device, is a semi-closed system that under 12 minutes, you can transfect 4 billion T cells. This is important for scalability, but also generate autologous CAR-Ts now the next day that are not activated. They are not exhausted. It's QC'd at the hospital and re-infused back to the patient. This is not FasTCAR . This is not possibly an overnight CAR that some other companies have been referring to. This is truly the only platform that allows you to do that. And why is this important? Brings down the manufacturing cost because there is no lentivirus. You can repeat dose.
You can do this at the hospital, so the turnaround time to the patient is truly overnight. No other system allows you to do that, and if patients need, it includes a safety mechanism. Now in the next generations, we have even a mechanism that downregulates the checkpoint inhibitor in the CAR itself, which reduces the cost further down and also the toxicity. This is truly paradigm shifting, and we are very excited about that. This is the portfolio of our CAR-T that both in hematological as well as the solid tumors have been advancing at various sites. In August of 2024, because we were pushing and we continue to push our PRGN-2012, we pared our portfolio, but we finished the most advanced through the phase IB for AML.
And we have decided and have communicated that the best way moving forward for this part is through strategic partnerships, which we are currently in discussions. So with that in mind, let's just take a few minutes on our AML. This AML, it's an UltraCAR-T that focuses on a CD33+ having a safety switch and membrane-bound IL-15. And an AML patient stage four that they really have known. The Moffitt Cancer Center pioneered this, started with this, and then Mayo as well as Fred Hutch, they have joined this. So it's a multicenter. And the first set of data from phase I was reported by Dr. Sallman at ASH, very exciting data, 28% complete responses in a patient population that they have a few months to live. But since then, we also have analyzed further our data and the expansion data that we have.
This is the first time that we are showing this data. Our translational group has identified specific biomarkers that you can stratify the patient population upfront and now drive that efficacy portion to a much higher percentage. What you see in that green bars, these are responders, and they are showing a specific biomarker B versus the non-responder, which is the red. Now you can basically, with simply as the patient comes in and looking at the test of the blood test that we have, identify, and we can identify the patients that are going to benefit with that characteristic. Can you imagine transferring that 28%, doubling or tripling the efficacy?
This is what we are in preparation now after submission of our BLA for PRGN-2012 to go to the end of phase IB meeting with the FDA and the discussion for a pivotal strategy, hopefully for approval. So again, I think I'm not going to repeat all of this, but we believe our UltraCAR-T is a paradigm shifting, which is truly overnight, has a much lower cost associated with it because it doesn't use the lentivirus, can address all the safety, has a favorable safety. We have never seen a neurotoxicity, no DLTs in these patients. And with the much lower, actually, concentration of cells, you can achieve objective responses. And going into autoimmune disease, and we have shown this data at the SITC now that actually we believe has the possibility to be the best first and the best in the class in that setting.
So with that, I'm going to thank all of you and thank Brian and JP Morgan for having us here. And we go to the question and answer. Thank you.
Great We're going to start the Q&A. Maybe, Helen, it would be great to maybe just kind of maybe anchor on just the upcoming potential. I mean, there's a regulatory timeline to the BLA that you filed for PRGN-2012. Just can you walk us through how the review process and the timeline towards your first potential BLA approval?
Yes, absolutely, so as mentioned, we submitted our BLA by end of December. We have received basically from the FDA that they are in possession of this BLA and the process of the review, which is for 60 days, has started. Upon the 60 days review, the FDA then officially gives you basically BLA acceptance and a PDUFA date for possible approval, and we are looking at the second half of 2025 for a start, the commercial launch, hopefully after receiving the approval.
And can you talk about just how the ongoing enrollment has been in the confirmatory trial? And as we think about the requirement of the confirmatory trial, is it required to finish? Do you need to finish enrollment first for the approval?
Yeah, no, absolutely. Great question. So we started our confirmatory trial that based on the alignment with the FDA, it's exactly a single arm with 35 patients, exactly as we have done in our phase I, phase II, with no placebo requirement and arm. And this started already in the third quarter. And we have currently enrolling patients to the confirmatory trial in a number of sites. And what is also very important to understand, when you have basically breakthrough and rapid approval path, FDA only requires that you start the confirmatory trial. You can receive your approval without finishing the enrollment or the data readouts. And I think that's very important because it's just the initiation of confirmatory trial that we have done so already. And basically, different sites are in the process.
Okay. And how are you thinking about the potential BLA label could look like? I guess what kind of language do you expect to see? Because there is a spectrum of patients that require surgeries a lot. So how do we think about just the requirement from a label standing on that point? And also as you pointed out, you had experience in a relatively wide range of age, right? And I think you point out there's someone at the age of one. So how should we think about just the language around age as well?
Absolutely, so currently, the label would be for adult RRP patients, and that's covering all RRP patients. The reason for that is obviously we have run our trials, and we have basically recruited the most severe patient population, and that was done by design because if you can achieve the results that we have achieved on a most severe patient population, it is logical to basically assume that with the less severity the patients would respond, and why would we say that all RRP patients, adult RRP patients at this point? The reason for that is our investigators and the surgeons that treat these patients; they are of the belief, and this data has been shown, that as the patient they start the surgery, the surgery is not curative, and as a result, it doesn't lead to the cure.
So these patients, after the first surgery, they're going to require more and more surgeries. And these surgeries are damaging and highly risky, sort of provide a high risk for these patients. So the surgeons don't want to do that. And when you talk to them, and actually one of the investigators was asked this question, they said, "Who would you give this to?" And they said, "Anyone who has RRP." So the label that we are seeking is, of course, for the treatment of RRP patients. And we believe in adults. Of course, there are plans for a pediatric indication later as we achieve the commercialization of the adult therapeutic part. And I think that also would be very beneficial to go to the patients that are below the age of 18.
Maybe just turning to a commercial, I think just going on the same point is that the label could be broad, but have you had any engagement with payers to get a sense of how they're thinking about what the bar is in terms of patient characteristics? And yeah, maybe let's start with that point.
Yeah, and we have had that, and I think best would be I give that to Phil, the Chief Commercial Officer of Precigen, to answer that based on the studies that have been done.
Yeah, we've had extensive interactions with payers, and we continue to do so as we get towards launch. We've covered the disease, the unmet need. There's a few things that have come through those discussions. Firstly, they recognize the high unmet need here. They recognize the inappropriateness of surgery to deal with this chronic infection in the long term. And in terms of discussing the value of our medicine and the innovation that it delivers, we've used that as the anchor point for discussions on price and value. We can expect there to be prior authorization when we launch, and that could be a mixture of trial, inclusion, exclusion criteria, treat to label, and an extreme medical exception.
Now, at the price points that we're discussing with the payers, we believe medical exception will not feature prominently, and it will be a mixture of treat to label and/or inclusion, exclusion criteria.
Yeah, and I think one thing that I can also add perhaps is that obviously we have not communicated on a price range. This is too early for that. However, clearly the analogs, and this is a gene therapy basically treatment, which will then respect that category.
Just on the commercial preparedness, how big of a sales force do you envision at the time of the launch? Can you also talk about just your low-hanging target doctors that you see and how big is that population?
Phil?
Sure. So the data that Helen mentioned, the electronic health record and claims record data is going to be extremely valuable for us in also defining, if you like, the heat map of patients and treating physicians. And we're in the process of finalizing that. There are approximately 500 fellowship-trained otolaryngologists in the U.S., but we believe there will be a concentration of those that follow the patients that will be in the academic urban centers, the large IDNs. And our footprint, as we finally determine it, will match that closely. So we feel there's going to be a relatively modest sales force required, supported by field medical in the field and reimbursement specialists and support as well. But it's relatively modest in terms of the number. But it's to be finalized based upon the heat map that I mentioned as we interrogate this data.
Got it. Okay. And I guess just on the plan about dose and capacity, Helen you talked about manufacturing. I guess as you think about your vector, I think it's different than a lot of the gene therapy companies out there. How different is it to manufacture, let's say, compared to adenovirus? Is there any nuance when it comes to making sure that you have the right commercial supply? Can you just shed some light on the difference?
Yeah, absolutely. So one of the reasons that we started our own regional GMP facility, first of all, we have, as we showed, a very, very seasoned leadership in this Gorilla Adenovector, which not only they develop these vectors, but also the manufacturing of that. And our head of manufacturing has more than 20 years of experience on this. And other aspects for it was important because we have a proprietary cell line that is very highly productive in production of these viral vectors. And that is very beneficial. And finally, we had the complete control of manufacturing. And this is why, for instance, during COVID, when all the other manufacturing sites were shut down, we were able to produce our GMP material and also put it in the clinic. And now we have transitioned to cGMP.
Based on the drug substance scaling up, we have every confidence that we have an appropriate number of doses to hit the ground running as soon as upon approval, both for doses for patients in the United States and also ex-US.
Okay. Maybe just in the last minute that we have, just maybe a recap on the big catalysts this year, what should investors be looking for?
Great. So obviously, we have submitted the BLA. I think the BLA acceptance is a milestone, and the PDUFA date that will be communicated based on the rapid approval will be six months from that point, and obviously, our readiness for the commercialization and some of the steps that we are taking over the next few months, we will be communicating to our investors and public in regard to the readiness to hit the ground running immediately after we receive the PDUFA. Similarly, we have been advancing the BLA submission on the EMA side, and we will be communicating on that. At the same time, of course, it's a very exciting and busy year. We will also be communicating on the end of phase IB meetings with the FDA for the UltraCAR-T, especially the AML side.
And as a result, also some of the strategic discussions that we have. So we look forward to having a very productive and exciting year in front of us.
Looking forward to it. And that's all the time we have. Thank you so much for joining us.
Thank you.
Thank you.