Good afternoon. Thanks for joining us for another session at the 42nd J.P. Morgan Healthcare Conference. I'm Brian Cheng. I'm one of the senior biotech analysts here. I'm joined by my associate, Sean Kim, who's in the audience. On stage, we have President and CEO. I'll pass the mic to Helen for a short presentation, followed by a Q&A. If you're joining us live, you can submit the questions through the conference portal, and if you're joining us virtually, you can also submit the question as well, online. Helen, the stage is yours.
Thank you very much, Brian, and thank you for having us here at J.P. Morgan this year. First of all, I obviously would be making some forward-looking statements, so please make sure that you look at the slides in details. With that, what I would like to start with about Precigen and what a transformative year we are going to have in front of us. I think we are very excited about the strategy of Precigen, which is designed to really address the value over time using two major platforms that we have. One is our AdenoVerse platform, and the other one is our UltraCAR. Both of them very well differentiated, and I will go to some of the details.
I also would like to mention that on Monday, we had a comprehensive press release that we have put out that addresses all of the major program. And today I'm gonna just highlight some of the programs, but please, I get your attention to read those. Basically, for us, this year is gonna be transformative. Why? Because near future, we are moving to BLA filing, and we are really excited that in a very record time, we have taken a program of PRGN-2012 from discovery all the way to the BLA submission by the second half of this year, and for becoming ready for commercialization in 2025. Also, we have established a very diversified clinical pipeline by using the two pipeline platforms that we have, both AdenoVerse, with obviously the potential of PRGN-2012 for commercialization.
And right behind that, with the AdenoVerse platform, is our PRGN-2009, using the same validated platform, but in oncology indications that are HPV associated, and we are looking forward to that program as well. And finally, our UltraCAR-T, which is truly a differentiated platform, and especially in the view of the past few months and the challenges that the cell and gene therapy, and especially classical CAR-Ts and the products have had, it even further have highlighted the advantages of our UltraCAR-T platform, and I will go through that. So with that in mind, let's talk about Precigen. What is the strategy of the Precigen? We basically have advanced our platform in such a way that you can actually first educate the immune system from within the patient and also have a platform, and that is our AdenoVerse platform.
Secondly, using our UltraCAR platform, that now you can ex vivo, take the patient T-cells and genetically modify them, return them back in order to basically see the enemy from within. And why is these platforms are differentiated? First, I'm gonna address our AdenoVerse platform. Our AdenoVerse platform is not like any other AAV platform or viral platform. What do I mean by that? First of all, it has a much larger capacity than any AAV or lentivirus or retroviruses have. It can go up to 12 KB, so you can imagine number of genes that can be presented in that. More importantly, this is not a one-shot deal. What you can do with this platform is to keep repeating this. This is not like AAV, you give it once, and then you have a neutralizing antibody.
Actually, you can keep repeating it, and you keep enhancing the T-cells while you are keeping the neutralizing antibodies at bay. Why? Because these are gorilla vectors, that the humans have not seen them before. So there is no pre-immunity to it, first of all, and because the mechanism of action pushes more toward the T-cell, it's quite actually enhanced in that. And with our clinical data have clearly shown that you can give it many times, and we have some of our patients received 16, 17 times, and we keep seeing enhancement of T-cells. And there is a very durable and a strong antigen-specific immune responses that we have shown in our clinical trial.
Finally, we have a very high productive manufacturing process, which, by the way, it has been applied for PRGN-2012, which we are doing the commercial manufacturing at our sites. That also not only brings down the cost, but the speed that we are going to have for commercialization. On the side of our UltraCAR-T, we are differentiated in the fact that we are non-viral, and this is not the old-fashioned non-viral platforms with all of the problems that we used to have. We have advanced it to be scalable and commercially viable. It's much safer, and especially with the lentiviruses, what we are seeing right now, that even some of them cause the proliferation of the CAR-T themselves and becoming malignant. Why? Because this is non-viral. It does not the potential of being inserted to the hotspot is much less than lentiviruses.
But secondly, we have designed safety switches that you can eliminate these T-cells at any given time. And we, of course, have designed mechanisms that you can expand and persist these cells directly in the patient. So you do not need to activate, and you do not need a centralized manufacturing in advance of that. Brings down the cost, it gives you the speed, which is overnight at the hospital, so you can imagine how fast we can get to the patient. And finally, the cost, and as a result of that, we can re-dose if we need to or change or combine with other UltraCAR-Ts. So let's look at our Precigen pipeline.
In these slides, what you see is the depth of our UltraCAR programs, which is shown in the below in light blue, the number of programs that we have in the clinic, and I will highlight some of them. But on top, it shows our AdenoVerse platform. And I wanted to mention that our PRGN-2012 is of the highest priority, and we are advancing this as rapidly as possible. With that in mind, let's talk about PRGN-2012 and where we are. PRGN-2012, it targets a recurrent respiratory papillomatosis. Okay, what is RRP or recurrent respiratory papillomatosis? This is a rare disease which has-- do not have any approved treatment by FDA. The only...
It's caused by, first of all, HPV 6 and 11 infection, and the patients that they have this infection, they develop this papilloma or benign tumors directly in the larynx or in the trachea. The issue there becomes, it affects their speech, and they can't talk or they can't breathe. There are some of the patients, they develop that from childhood, some later on in a stage of life through infection. What basically happens here is once these tumors grow, patient has to go for surgery. There's no other options. These surgeries are recurrent, and it gets worse. Some of our patients, they start with 1, and then after a few years, it leads to more and more surgery because a surgery, it leads sometimes to further infection, and then the patient requires even further surgeries.
So this is a devastating disease, and you see the picture there with these tumors actually now blocking the trachea and then right on top of a vocal cord. We have had patients that they have had over 300 surgeries over their period of time, and the ones that they participated in our clinical trial, on average, have had 6-7 surgeries, and some of them up to 10 surgeries in a prior year. So you can imagine every month to take your child or as an adult, going for a surgery in order just to be able to breathe or talk, and what a devastating disease this is. So with that, first of all, I want to really thank our patients, RRP patients, for participating in our clinical trial, and also our close interaction with the RRP advocacy group and the leadership.
This has been instrumental for development of our PRGN-2012. With that in mind, let's look at the mechanism of what is the PRGN-2012. As I mentioned, this is a gorilla adenovirus that has been designed to express the epitopes of HPV 6 and 11, and basically train the T cells, army of T cells from within, that can attack the cells that are infected, and especially these cells that they exist in the trachea or in the larynx. The beauty of this treatment is very simple. The patient receive a simple subQ injection, like when they receive a flu injection, flu vaccine, right? And then with that, once these gorilla vectors are injected, they train the T cells of your own body to see the epitopes that are causing this infection or the virus that is causing this infection. They expand.
They are now a trained army that can attack those cells that are infected and destroy them. And by doing this, you are getting to the root of the problem. The surgery, all it does is like mowing the grass. You cut it, it comes back. However, by using PRGN-2012, we have shown that you train the immune system, and we published on this in a Science Translational Medicinel this past year, very comprehensive of the mechanism of action, and showing that it goes to the root of the problem and basically taking those cells, infected cells out, and therefore, the cells are not growing. So what we have done, and I'm extremely proud of our Precigen team, we have really spearheaded the treatment for the RRP in the field.
The team has done an outstanding job from the start of the discovery program from 2020 to receiving an accelerated BLA by August of 2023. As you can imagine, in the world of the drug development, this is outstanding record... Really, Precigen has become a leader in this field by receiving the first BTD, breakthrough designation in RRP indication, and by receiving the first also accelerated path for approval from FDA last year. We are really excited about how fast and agile we have been in this field for our patient, and I'm very proud of our team at the company. A little bit of a highlight of our data on PRGN- 2012.
Our clinical data, we have already have in a full phase I and the expansion of a phase I, we have demonstrated that we went to the most severe patient population, patients that at least require three surgery or more. And also, even though from the perspective of patients, investigators, KOLs, reducing the number of surgery, it's extremely meaningful. We went a step beyond that, and as an endpoint, we design our trial in such a way that not only do you decrease the number of surgery, but actually you go to as an endpoint with a complete response, meaning that you do not require any surgery for twelve months. And we followed this patient after a treatment with four injections, sub-Q injection of PRGN-2012. First of all, the route of administration, extremely easy for...
And this is what we are hearing from all of our KOLs, investigators, and the patients. Secondly, the safety that we are seeing is only grade 1 and grade 2. Our investigators have associated that very similar to the kind of result that you see after receiving a flu vaccination. There's no device requirement at this point. And when you look at the severe patient, and you see those in that orange bars, that some of them in the prior years have had 8-10 surgeries. After receiving a course of PRGN-2012, they went to 0 follow-up of 12 months.
But on Monday, we actually updated, and we are really excited that these patients now, we have been following them for over two years, and they have stayed in a complete response, have not required any surgery, and of course, we will continue to follow up these patients. But at the same token, in the rest of our patients, we also see benefits. 83% of our patients, they reduced their number of surgeries. None of our surgeon patients got worse in this trial, and no safety issues. So we have communicated.
We are looking forward to showing our full phase II data by the second quarter of this year, and through the accelerated path that we received from FDA, they have agreed that our single-arm phase I plus single-arm phase II, which we enrolled fully last year, and the follow-up will be finished, and we will be reporting on the second quarter this year. That will serve as our pivotal as is, and I think that is a great outcome for the patients on a RRP with the result we are seeing. And more important in advance of not only the safety, but the durability that we are seeing, which is really significant, and our investigators, they love this. So with that, we are on the path to submit our BLA in the second half of this year, and our company is getting ready for commercialization in 2025.
Just to show you the potential of the commercial launch for our 2025, obviously, I spoke about the preparation for BLA submission in the second half of this year, and we have been looking at the significant potential and market opportunity that this drug product has. This is... We believe it's under conservative Science for the U.S., what we are reporting on ex-U.S. We focus our commercial activity on a very concentrated prescriber base. Finally, under the leadership of Jim Shaffer, the head of our commercial now, we are preparing for the commercial launch for 2025, and this is really a transformational year for our company. We are going from a biotech company that was basically clinical R&D to eventually a commercial company, and that's quite exciting.
So with that in mind, we have been assessing, and we are looking at the key characteristics that is associated with PRGN-2012. Not only we have been able to reduce number of surgeries, we have eradicated the surgeries required at least up to 24 months of the follow-up as of now. The durability of this is very appealing to our KOLs and investigators and prescribers that we have talked to. They prefer the route of the administration because it's a simple sub-Q, like a flu vaccine.... And finally, the reassuring safety. The comprehensive package that goes, which is also associated with the immunological responses, that is in direct parallel footstep with the clinical response, it's very reassuring for this drug product and puts it in a category by itself.
So with that, using on the same vein, the platform that is now validated with our PRGN-2012, we have applied it to PRGN-2009 to really address the HPV-associated cancers. The mechanism of action here is to target HPV 16 and 18, which is cause of these HPV-associated cancers such as cervical, head and neck, anal. And the same way, simple sub-Q administration, training the immune system now against the tumors that express the epitodes of HPV 16 and 18 and eradicating those tumor cells. So with that, last year at ASCO, we presented the full phase I and expansion cohort, and interestingly, when we used our PRGN-2009, even in the patients that they had failed checkpoint inhibitor, we were able to basically achieve 30% objective responses and durable responses.
For instance, our complete response well over a year. With that preclinical data, we have moved now. Not only we are in phase II in head and neck, but also we received the IND for phase II/phase III, pivotal in cervical cancer, and we are very shortly enrolling to that, and we are very excited about this. And finally, a few words about our UltraCAR-T Platform. That is basically the way it's designed is to allow non-viral electroporated T-cells that express the CAR, the membrane-bound IL-15, which allows for activation, persistence of these cells directly in a patient, and a safety switch, which allows for elimination of these cells in case of any toxicity under a same promoter, that you will then achieve a homogeneity of the drug product.
We have designed this in such a way to answer majority, and I would say, the shortcomings of classical CAR-Ts, as well as off-the-shelf, as you see in this table. We now can basically do a non-viral using our UltraPorator, 4 billion T-cell transfected under 12 minutes. This allows us scalability for commercialization. We have achieved overnight manufacturing at the site of the hospitals without Precigen employees being there. And now we are in number of the sites such as Mayo Clinic, Moffitt, Fred Hutch, University of Washington, and soon to be NIH added. The safety has been very favorable. We have not had any DLTs, no neurotoxicities. We have shown in vivo persistence and expansion, and much less cost of manufacturing time to the patient and the safety.
With that, the mechanism of action, what you see in this slide, this is exactly as it takes place in the hospital, and currently our patients are going, and we have treated upward of 70 patients in our trials. This is not our imagination, this is not what we hope to achieve. This is what is happening currently at the hospitals, and patients are being treated. We have data, clinical data, that, for instance, on our AML studies at ASH, was presented in the patients that they are basically hospice-bound. We had 27% objective responses. We are moving that to phase I-B. Through that, and as we guided, we will be reporting on data on that by the end of this year and speaking to FDA. All of the other CAR-Ts are advancing rapidly, and we are really excited.
Today, I also want to introduce one new CAR-T member, our PRGN-3008, which targets CD19, but also have the capability of downregulating the PD-1. And we believe, in the next slide, I'm gonna show you some preclinical data, that first of all, the design of this, it has all the bells and whistles of our UltraCAR-T. Safety switch in this case of toxicity, membrane-bound IL-15 for expansion, so you don't need to activate or manufacture billions of these before and keep it for weeks in the centralized manufacturing facility. It's done at the hospital overnight, and with the ability of downregulating PD-1, which then you don't need to combine with checkpoint inhibitors for reducing the toxicity and the cost. But what I'd like you to take a look at is on the right-hand side.
You see the control animals, all those blue and yellow greens that you see, that is a tumor. On a conventional CAR-T, you see there is a benefit, but not that much. There are few animals that they are tumor-free, but the rest of them, they continue to develop the tumors. But I'd like you to take a look at that UltraCAR next generation, and now you see every single one of those animals have cleared the tumor. This is the power of UltraCAR-T. Even though we believe in the oncology indication, we might not be the first in the market, we believe we can be the best in the market. But more importantly, we are preparing our CAR-T also to enter to phase I in immune diseases and autoimmunity. And in that setting, we believe we can be first and best in the class.
Why we are saying that? Simple. For a chronic diseases, the safety bar is much higher than oncology indications. You have to ensure that these patients, that they live long time, you are not exposing them to the safety issues that the stage four perhaps is tolerable for a cancer patient that doesn't have any other option. Number two, with the chronic diseases, you generally have to redose. The manufacturing of all the CAR Ts that are going in that direction would not allow for that. We believe, based on the safety switch that we have, based on the preclinical data that we have put forward, based on the low cost of the manufacturing and fast overnight manufacturing, this makes the best candidate to enter to the clinic for autoimmune diseases, and we are pushing forward by the end of the year toward this.
So with that, this is the vision of what we think the future of cell and gene therapy and medicine should be as far as CAR Ts are concerned. The library of the CARs and plasmid that exist in the hospitals as the patient walked in, the oncologists, they ask for a specific CAR, CAR to be basically manufacture overnight. The next day, the patient receive their own autologous T cells, much lower cost, faster, safer, and if they need to be redosed, they can do that. If it needs to be combined with another Ultra CAR, they can do that because the costs are short and low, and then you can move on. So with that, I thank everyone for listening to this pre-presentation, and look forward to the questions.
Great. Thanks, Helen, for the presentation. Let's kick off with the Q&A. You know, for those who are in the audience, if you have any questions, you can raise your hand. We have a runner on the floor. For those joining us virtually, you can always submit your questions on our portal. So I want to start off with PRGN-2012, you know, RRP. This is a great—this is gonna be a, a very, you know, transitional—transformational year for you. You know, given that you're gonna have pivotal data this year, you're gonna start prepping for BLA. At the same time, you're also you know, starting to prep for the launch as well, right?
Yes.
So maybe just one is on, you know, your preparation currently. You know, as you think about the commercial infrastructure needed to launch this product, how big of a sales force do you need to launch within the U.S.? And also, you know, as we think about, you know, just from a modeling perspective, right, how should we think about the launch trajectory, based on what you know, and also, you know, what you're hearing from KOLs?
Absolutely. Excellent question. First of all, for our preparations, based on, we have already Jim Shaffer, who's in the audience, has joined us, in 2023, we're really making the organization prepare for this, and we have started the studies and research marketing studies and everything else, which in the very near future, we will speak more about that. But what we have seen is that obviously the primary, there are close to thousands of ENT, but really, the specialists that they treat these patients, they are close to 500, basically, laryngologist, a specialist for the larynx and trachea. And our focus is gonna be on these physicians.
Because we can narrow this down, we believe that we can have a very effective commercial force that can be interacting with these physicians, and especially in the centers of excellence and also in their practices, that can position the PRGN-2012. Obviously, all of the commercial units are being built as we speak, and there are activities are ongoing on the marketing side, payer side, medical affairs, and we are really excited about this, that we will be prepared for a launch for 2025.
So just to piggyback on your comment, you know, related to the $500. So I mean, the way how I think about it is more like a, you know, reverse pyramid, right.
You know, the tier one, if I may-
Yes.
Start labeling things.
Right.
and put them in a bucket, is the tier one is the 500 initial set of doctors, and then potentially can expand to the thousands of ENT doctors, right?
Right.
So how big of a sales force would you need to kind of, you know, make sure that you penetrate well into the initial 500 doctors who are your initial targets? And where are you also in, you know, onboarding these sales reps and the rest of the sales infrastructure?
Right. I think, as you said, this is an inverse pyramid, meaning from thousands to 500 and focusing on that 500. And the way we assume currently, we obviously we are looking at details on how many sales rep is needed, and we will deploy the right amount of sales rep that to ensure a very successful launch. And are we talking about at the moment, we are not looking at more than 20, but this is we are narrowing further, and Jim will be speaking to that in a very near future with the detail, actually, launch plans and preparation. But it will be a very focused sales group, because actually, the number of the physicians that we have to target is limited to 500 and centers of excellence that they are treating majority of these patients.
We have spoken to KOLs, and number of them, they have, in their practices or in the hospitals that they are practicing, they are treating 50, 70, 80 in these settings. So clearly, we can focus on those and start the launch very, very rapidly.
As we think about, yeah, of course, there's a component of efficacy in the ongoing pivotal phase II, and that's certainly a part that, you know, we all have to care about. But, you know, when we think about the rest of the BLA package, right? What additional informations outside of... I think earlier in your prepared remarks, you said that there will be the phase I, the single-arm phase I, and the single-arm phase II
that will be in the data package, right?
Absolutely.
What additional information do you think that will be, you know, that we should also think of when you-
Yeah.
when you're starting to prepare the data package?
Absolutely. For BLA, for any BLA, obviously there is a non-clinical, clinical CMC package that has to be submitted. Of course, one of the things that we have been very good at, for instance, on a clinical side, and that's why FDA has basically our phase I clinical, basically, design is exactly the same as phase II. That is the reason that in the original guidance from FDA have said that we can use and combine these two together, and have given even us the confirmatory trial can be exactly the same way as we have executed. Those packages are being getting ready, and as you know, as part of our accelerated approval path, we can go for a rolling BLA, and we will be taking advantage of that, submitting these different units.
Then, of course, our CMC, which again has been very similar to the material or commercial CMC, to the material that we have already generated for a pivotal phase I, phase II, and those packages will be submitted along the line for that. So those are the components of the really major components into a BLA, and we are in the process of actually putting all of that together, and then, as we mentioned, the guide would be for second half-
Mm-hmm.
of this year for full submission.
Any questions from the audience? So, on capacity, in terms of, you know, at launch, how should we think about that, and where does it ramp up to, you know, at, let's say, a year to 2 years down the line?
Excellent question. What we originally, as we were going through our pivotal, we were preparing our own manufacturing facility on site. By the way, all of our GMP material and material that was used in phase I, phase II pivotal, was already prepared at our own manufacturing site. So that's very important. And of course, our manufacturing team continues to do that and prepare for the commercial launch. And we are confident because of also the cell lines that they produce, this viral vector, which are very efficient, they have a high efficiency. We believe we will be in a very good position to have material, enough material for basically a start on enrollment of the commercial and treating patients, obviously, after receiving in 2025, the approval from FDA.
It will be a very rapid, I think, movement from after approval to supplying the material to the patients.
Late last year, you talk about, you know, the potential for potential transaction, you know, around AG019 and CAR T. You know, on the point of CAR T, do you have any update on where you stand or any thoughts on CAR T? And it's interesting that you also unveil new CAR T assets, right? So, how does that also align with your latest strategic plan?
Absolutely. Great question, Brian. First of all, I think the ongoing discussions on a partnership, it is ongoing, and we are excited about that on both platform. As we... You know, the AG019, we really believe that this is gonna be extremely beneficial for T1D, and now currently we are in discussions. I will leave it at that, and we will report back soon. On the level of UltraCAR-T, especially in the view of the challenges that has come up from a regulatory perspective, we really have now been positioned almost as a frontrunner in this field with a really differentiated platform, and I think a number of companies have taken notice of that, and especially the more of the clinical data that we have shown.
For instance, on our AML side, which we are very excited and we communicated, we will be reporting by the end of this year on a phase I-B expansion, and getting ready to have discussions with the FDA on a regulatory path for this. Which we hope that we can move it very rapidly from a line 3 or 4 to front lines here. I think this, in conjunction with the safety, the efficacy that we are showing, and the benefits of this platform, is positioning us in the view of many of the partners, that they see that this is something different. And why CD19? And to the point that you are asking, first of all, we really have used the past 2 to 3 years to establish the platform, modify it, get it to the point that it can be scaled and commercially viable.
At that point, we didn't have the rights for our CD19. We finally got back our rights for CD19, but meanwhile, now we have validated our platform, and now we have a validated target plus a validated platform in the clinic. That is the reason we believe we have the best in the class, because it addresses the shortcomings of the field, and we are able to do that. Also, we see the benefit of our CD19 next generation for truly for chronic diseases, which again, it position us, not only no one is really a front runner right now in that, so it's a great point of entry for us.
So autoimmunity?
Autoimmunity.
Okay.
For instance, lupus.
Mm-hmm.
It's a great point of entry for us. At the same token, we can be the best because we have the characteristics in our UltraCAR-T, that to our knowledge, none of the other CAR-Ts that are going in that direction currently have, and that's our advantage.
So we have 30 seconds left.
Sure.
But just to kind of going back to that point, is that so? Are you... you have in vivo data in oncology, and, you know, CD19 is now making a headway into autoimmune.
Right.
Do you see one or the other? Which one is your favorite?
It's a very good... It's like, choosing a child. I think it's somewhat of a difficult question. For our oncology, we clearly have, we know what, the indication and, doses and everything that we need to go, so that would be very rapid. On the autoimmunity side, the advantage that, we have is a fast manufacturing. So I see that we can basically position this very rapidly forward. But I also wanna stress one other point. That does not mean that we are taking our eye off of the ball from PRGN-2012. That is our highest priority for the company. It remains the highest priority for company to the point of commercialization, and then while we are doing that, we will be advancing our other parts of portfolio.
Great, Helen. Thank you so much for joining us-
Thank you.
We look forward to a robust year in 2024. Thank you.
Thank you very much, Brian.