Precigen, Inc. (PGEN) Earnings Call Transcript & Summary

Thanks again for tuning into the JPMorgan Healthcare Conference. I'm Eric Joseph, senior biotech analyst. Our next presenting company is Precigen, and it's my pleasure to welcome and introduce President and CEO Helen Sabzevari, to tell us a little bit about the company. [Operator Instructions] Helen, thanks, for sharing some of your time with us this afternoon.

Thank you so much, Eric, and thank you for the opportunity to present at the 39th Annual JPMorgan Healthcare Conference. And I also want to -- hope that all of our listeners and their families are safe and healthy as we begin 2021. Before I start the presentation, I also want to remind everyone, I will be making some forward-looking statements, which please pay attention to the slides that it's in Slide #2. With that in mind, I think we should start and going to Slide #3. What I really want to touch base today is, first of all, get your attention on what makes us different and differentiate Precigen from other companies. And as you see in this slide, the platforms that we have, the UltraCAR platform, our AdenoVerse platform, our microbial platforms are what is really genuinely unique. And hopefully, in the next 20 minutes or so, I'll give you some preview on how these have enhanced our portfolio. From the perspective of our portfolio in the next slide, what you see is our clinical portfolio, which we have used this platform across in various indications. And especially, what I would be talking later on today is about 2 assets, PRGN-2009 and 2012, which we are very excited about. Our AdenoVerse platform in HPV and RRP, basically patient population. And I will be giving some clinical and preclinical data, which is extremely unique and exciting today. With that in mind, for the next few minutes, I will spend some time recapping and summarizing what we accomplished in basically 2020 and reported on our R&D Day. And one of those aspects was our microbial platform, ActiveBio, which is AG019 in Slide #6. Basically, last month, we reported on Phase Ia, Phase II data, both as a monotherapy and combinatorial with teplizumab. The safety, we showed safety data that has been excellent in this patient population as well as for the first time, the clinical activity for both monotherapy as well as the combinatorial with teplizumab. And we are looking forward, in 2021, to extend the data as well as move these assets very rapidly in a type 1 diabetes and with maybe a very unique regulatory pathways forward. From the perspective of our UltraCAR, in December, what we have shown, and if we go to Slide #8, this is the platform that is very unique and differentiated for us from all other conventional T off-the-shelf CARs as well as TTRs. The uniqueness of this platform lies within our UltraVectors that they have the capability of expressing multigene simultaneously, therefore, delivering the homogeneity of the drug. Today, I was talking with -- in a panel with Scott Gottlieb and others that this is one of the factors that's extremely important, especially as we bring the drugs forward to the commercialization. And this UltraVector allows us exactly to do that, come up with a homogeneous cell population that can be infused back to the patient. Also, we have designed these cells in such a way that now we have, basically, gotten rid of the expansion outside by introducing the membrane-bound IL-15 and directly expanding these cells and manufacturing them in a sense in the patient, and these cells are capable of persisting simultaneously because we don't expand them outside. They are capable of being younger, and therefore, last longer in the patient's body. So basically, what we have done through our UltraVector and the use of nonviral delivery system, transfection system, it's allowing the hospitals to basically, overnight manufacture this autologous CAR-T for the patient and next-day infuse it. As you see in this diagram, the patient basically walks in, the apheresis happens. In the afternoon T cells are separated. Last year, we introduced our UltraPorator, which is a specific transfection unit, semi closed, which now reduced the time from hours to minutes to transfect billions of T cells under 12 minutes. Why is this important? Simple. What you need is that make this scalable, reduce any kind of risk to the production that you have and maintain the time that you want. And this allows us to move this platform towards the commercial viability. This is very exciting. And what we have done is, not only this is -- this is not a diagram anymore. This is a reality of what is happening in the clinic. So with that in mind, we really have turned the UltraCAR platform, the ease of off-the-shelf, but without all the issues that is associated with the manufacturing of it with basically safety part with the number of cycles that you have to give and the price factors that are associated with them. So with that, let me just recapture in Slide #9, what we presented last month, and we are very excited about this. For the first time in a solid tumor, PRGN-3005 in ovarian cancer. What we reported preliminary data on 6 patients. At the lowest doses, if you can imagine, the first dose cohort received between 30,000 to 100,000 cells per kilogram of a patient. Depending on the weight of the patient, this translates to somewhere between 3 million to 7 million cells only with no lymphodepletion at all in these patients. And what we were able to show in this all patients across. First of all, these cells expanded and persisted. This was extremely important because the whole differentiation marker and changing the paradigm about this. The safety was excellent. The patient showed no CRS, no DLTs, no neurotoxicity. And you have an example of 1 of the scans of the patients that in some of the lesions -- these are patients that they have failed anywhere between 6 to 9 prior therapies, extremely sick patients. And you can see that we have complete responses, partial responses, stable diseases on lesion. In actually 50% of these patients we had a reduction, 50% reduction in tumor lesions, which is, for the first time, this is a platform, no one has ever done this before directly manufacturing and also seeing clinical activity on lesions at such a low doses, by the way. When you look at other CARs or TCRs, you are in hundreds of millions, we are between 7 million to 20 million cells. Similarly, on our hematological one, we reported the first 9 patients, both in arm of non-lymphodepleted in AML and lymphodepleted patients. And we showed -- again, across all 9 patients, we have seen very encouraging, both expansion and persistence. Our manufacturing in both trials have been 100%. And what we showed is signs of clinical activity, again, at very low doses. In this trial, some of the patients received between 1.5 million cells to 3 million cells on the first dose, and in second dose upwards of 20 million cells. So you can imagine how low the dose is, and 6 of the patients had no lymphodepletion, especially the one that you see in the bottom half of this slide. This is a patient, a 69-year-old patient, that was in hospice. These patients, they have a matter of months to live. And as you can imagine, when you're in a hospice, it's a matter of weeks. And this patient came out of hospice to receive this therapy. And you can see that's -- up to 7 months that we had followed this patient. This patient showed expansion of the T cells, the purple line, as well as persistent and it parallels the control of the blast cells in green line and reduction of them with a biomarker of the porphyrin, which you can imagine them as a little bombs that these UltraCAR-T cells drop to kill the tumor cells, right? And we have seen also the traffic of our UltraCAR from the blood to the bone marrow, which is the right-hand side diagram, expansion in the bone marrow as well as the control of blast cells. These patients, by ELN, it was considered a stable disease. Why not a complete response or resist responses? There is other factors in AML, such as platelet counts that affect, despite of even the reduction in the blast cells or more than 50% reduction, you still -- if the platelets is not back, for instance, the category is different. We also have had a second patient at this point that it was considered as MLF, which is a morphological leukemic-free state. And we are very excited about this at the lowest dose in this trial. So these were reported, and I highly recommend for those of you who are interested. There were much more data. This is just a sample that you can go to our website and actually take a look at all of the slides that are available. So with that, I would like to get your attention to Slide #10. A lot of people ask me, Helen, what is the vision with the UltraCAR platform? And for us, it's simple. The vision is that you bring an ease of a treatment to a patient specific to them with their own autologous T cells, but with a very rapid turnaround and the rapid cost that you are not making a treatment that is only available to certain people, but the treatment can be available to everyone. How do we see this? If you look at this slide, the way we envision through our UltraVector now the proof of manufacturing that we have done in -- directly in patients. We envision that we have number of UltraVectors with different targets. Imagine, they are sitting in the little vials on the shelf of the pharmacy in the hospital. As the patient walks in, the patient is diagnosed with lung cancer, pancreatic, ALL, multiple myeloma, any of them. The oncologists look at the molecular profile of the tumor, they decide on the target, and they tell the GMP facility at the hospital, prepare the cells of the patient overnight with this UltraVector against CD33, Mark 16, mesothelioma, any of these targets that you wish or others. And the next day the patient receives that. If the patient needs to receive a second dose, you can redose because this is overnight manufacturing. Now let's imagine a patient has a heterogeneous tumor that might not just express 1 antigen, but also others. You can dose with different UltraCAR simultaneously, or in the cases of the hematological diseases, sometimes you have escapees, tumor escapees that they mutate and now express other antigens. Now you can redose with a different CAR. This is all possible with this platform, whereas no other platform has the flexibility and diversity to do this. It's not possible. You cannot spend $0.5 million every time to come up with a different target, or you cannot prepare hundreds of thousands of doses for every 1 of this. However, with the UltraCAR platform, we can approach this UltraCAR library. And this is our vision for our future. And this is what we are now, as we speak, moving toward. So with that, I think I'm going to wrap up our summary of what we presented, but I'm also extremely excited now to take you to the next platform that we have, which is AdenoVerse platform. And if we go to Slide #12, this is truly a leading adenovector technology. Why do I say that? This is a library of gorilla vectors that they have a very high payload. They are unlike Ad5 or other viruses because their payload is quite large. You can put a number of genes or switches in them. But 1 other very important perspective on this is that you can repeat dosing. Why is that? Because we have tested thousands of donors, healthy donors and humans, both in U.S. and Africa. And there is very little or no seropositivity, meaning no immune responses -- prior immune responses to this. So you can give it multiple times. And preclinically, previously, we had shown, if you do so, you can keep enhancing the immune system, which is not the fact with other viral platforms, right? So in 2020, what we did against all odds and all -- what was going on with the pandemic, with our collaborators at NCI, which I am indebted to them for the patients and for our organization, we brought forward PRGN-2009. In the next slide, Slide 13, you see that we targeted the HPV associated cancers. This AdenoVerse or adenovirus was built to basically target HPV-16 and 18. And NCI preclinically, which is what you see on the right-hand side, what has shown that upon treatment of the mice with the tumor, very clearly, they reduced the tumor burden significantly upon increasing the HPV specific T cells. So in next slide, in 2020, in, I believe, was April or May, that we cleared the IND for PRGN-2009. By the way, this is the first time that we have this platform in the clinic. During the pandemic, as we clear this, our NCI collaborators, they dosed the first patient in August of 2020. Again, really agility that was shown here was amazing. And I am really proud to say today, and excited that, as I'm reporting to you today that NCI has finished the monotherapy arms of this clinical trial. Six patients were treated at 2 different dose levels. And the safety has been excellent. There has been no DLTs upon repeated dosing of these patients, and this is extremely important for the platform that is the first time in the clinic. And they have already initiated the combination of PRGN-2009 with the anti-PD-L1/TGF-ß Trap of GSK, Merck KGaA, and this has started already. So with that in mind, now let's go to the next slide, slide #15, which I'm extremely excited. If you remember, all throughout past year, we have mentioned that one of the advantages of this platform is that you can have number of genes in there, and you can multidose. And this is exactly what we did with the PRGN-2009. Not only we put epitopes that target the HPV-16 and 18, the typical ones, but we had identified new epitopes. And we incorporated those into the design of this off-the-shelf immunotherapy vaccine directly there. And the first group, the first 3 patients, you see the data here. Upon repeated dosing of these patients what you see on the right-hand side, both CD4 T cells and CD8 T cells of these patients. You can see that 100% of the patients treated at dose Level 1 showed significant responses, increase in HPV-16 and/or HPV-18. This is speaking to the power of this platform by, basically, increasing and enhancing the number of the T cell upon repeated dosing, which other platforms are not capable of doing. Also, we saw increase in the magnitude and the breadth of the immune responses with repeat administration. One of the interesting aspects or the way you can think about this, imagine that this multi epitope design, which allows now to the expansion of directly inside the patient, T cell memory against this epitope, it's equivalent or you can have the analogy of injecting number of TCRs, which, in cost and manufacturing, will be tremendous. But here, with basically a virus, we are able to do that. And this is why I'm so excited about this. And by the way, about the patients that have received this, I would ask you to stay tuned for the clinical data that the NCI will be presenting this year. And we are really excited about this as we move forward in 2021. So with that in mind, as we go to the next slide, as we mentioned, the AdenoVerse platform has the flexibility to be utilized across indication. In this slide number, I would say 15 now. It's -- as you see, and we reported early on this January, we cleared the IND for PRGN-2012, which targets basically HPV6 and HPV11 in the RRP, the recurrent respiratory papillomatosis. These patients, basically, they develop these benign tumors in the respiratory tract. The picture that you see on the right-hand side, this is very typical. There is no cure for these patients, as you can imagine. The only way to deal with this is, every few months, they have to go for surgery. And you can imagine a child having this, adults having this. And this is why we targeted this disease with the capability that we have with our AdenoVerse platform. And the next slide, #17, we designed a specific adenovirus that contains not only the HPV 6 and HPV 11 epitopes, but it has special designs and other epitopes involved in it that can give a very broad coverage. What you see on the left-hand side is a preclinical data from samples of patients that you can activate their T cells -- the RRP patients that you can activate their T cells with this off-the-shelf immunotherapy and expand the T cells significantly to basically kill these infected cells. And this is very, very important. How we see utilizing this in clinic? As we cleared the IND, as you can see, the Phase 1, the patients will come in and they receive 3 x 3, 2 doses, different dose cohorts of this drug for 4 times, and then they will be followed up. As they have received the doses, obviously, the first thing is safety and the dose escalation. And then the follow-ups are for the recurrence of RRP. So we are very excited, and we are doing this also through our CRADA with the NCI and moving it forward in 2021. And finally, in the next slide, now PRGN-2013. This is the first time we are unveiling this target. This is one of our preclinical targets in infectious disease that is moving very rapidly towards the clinic, is targeted against chronic hepatitis B virus. As you can see, that's a huge indication across the world. And we have designed a specific adenovirus that addresses not all the known epitopes that other competitors, for instance, also have included their vaccines, but we have identified a number of other epitopes that because of the payload that capability that we have, we can include and we have done so. I would like to get your attention to the upper right-hand side, the bar graph. The colors that you see, it simply represents different epitopes, response to those antigen epitopes. The more that you have, the better it is. That means your immune system are recognizing it and basically killing the infected cells. You can see our competitor's vaccine on the left-hand side. You can see the epitopes are limited, the responses are not as enhanced and comprehensive. On the right-hand side, the different color shows that T cells are being educated to against different antigen or epitopes, and they pick the, basically, enemy and they can kill. And you can see the broadness and the breadth of the response here. In the lower hand side, this is directly in vivo, and we are directly comparing the response of cleaning the infected cells, HBV infected cells compared to our competitors, and that is the purple line. And you can see that are AdenoVerse PRGN-2013 does a much better job, significantly better than the competitors. This is a very exciting program because this is an unmet need with a huge number of the patients across the globe -- in 257 million patients across the globe for this. And this is an indication that leads to cirrhosis of the liver, damage to the liver and eventually to the hepatocellular carcinoma in the patients. So you can see that it's quite important, and we are really excited about moving this program. So with that, what I would like to do is summarize. Last year, when we came to JPMorgan in 2020, as you see in Slide '21, we set a very aggressive number of goals for ourselves. And I am tremendously excited about reporting that after the -- in 2020, the team at Precigen, and our collaborators, they have achieved every single one of these goals despite of all the challenges and the pandemic, COVID pandemic that has been going on. And I cannot be prouder and more privileged to stand to the team, both internally and externally such as this. So this has been an incredible year for Precigen, quite exciting. And we are looking forward to 2021. And as you can see in the next slide, this is Precigen goals for 2021 to complete not only the dose escalation, but to start the expansion and redosing of the patients in 3005 and 3006, which we are anticipating, and we will report on this as we move forward. We are going to present and submit IND application for new CAR-Ts. And this is quite exciting for us in 2021. We also will be -- present the interim data on our PRGN-2009, and I will ask you to stay tuned. This is quite an exciting platform. Initiate the Phase I trial for 2012 and dose these patients, and initiate the IND-enabling studies and move the HBV off-the-shelf immunotherapy very rapidly towards the clinic. And finally, we present further data on our autoimmune asset AG019 Phase Ib/IIa and move this to the next levels clinically. So with that, I thank you for listening, and I will return control now back to Eric.

Okay. Great. Helen, thanks for that presentation. Just picking up on the strategic vision that you laid out at the top of the presentation, what you're sort of describing here is an on-site sort of decentralized manufacturing system. So can you just kind of talk to the type of quality controls and assurances, I guess, that you think might be required to make this -- to have this kind of system implemented -- this manufacturing process implemented? Would you need to have dedicated technicians sort of on-site for the individual or for the UltraCAR-T products?

Yes. So thank you for the questions. In regard to this platform, what we envision, as I mentioned, this is a platform that needs to be simple enough and easy enough to be handled on the site. The 2 sites that currently are doing this, none of Precigen employees or technicians are there. So the SOPs are written and advanced and evolved to the point that, basically, like anything else, you send the SOPs and the technicians in the -- any of the GMP facilities, or the clean rooms in the hospitals, they basically follow the steps that is given to them. And with that, when we say 100% success in manufacturing, that's exactly what we mean. Because it's not Precigen, it's the hospital, basically clean room. These are the same people that they are doing their bone marrow transplant. These are the same technicians that work in day in on a simple basically assays that it's done for the hospital. So one of the other reasons that, Eric, we introduced the UltraPorator was exactly that one step that would have been basically time-consuming and allow, because of the number of the hours to transfect higher number of cells, would have allowed perhaps some mistake, would have been that arena. And that's why we developed, anticipated for commercial viability and in discussions with the FDA actually very early on, what are the needs here? And what kind of a test needs to be done, for instance? And we took that, and we implemented in coming up with the semi-closed system that, as you saw, there is a cartridge. And the technicians, all they have to do is press the program, a start, put the cartridge, it takes up to 4 billion T cells in that, simultaneously transfect them with the UltraVectors and wash the cells into a bag that you put in an incubator overnight. And then the next day, you basically take your UltraCAR and QC them according to what we have discussed and the test that needs to be done, which, by the way, happens right at the site in a clean facility and the patients receive their own T cells.

Okay. The preliminary data that you presented with the PRGN-2009 program, a Phase I study that you're conducted with the NCI. Maybe I could get you to elaborate on that trial a little bit more in terms of the tumor types that have been enrolled into the study so far. And you're seeing some promising antigen-specific T cell responses. Is -- are those the type of responses that might -- you might anticipate drive tumor responses, I guess, over time? And maybe you could sort of speak to the rationale for combining with the TGF-beta [indiscernible] also off of it.

Right. Yes. No, great question. So the type of -- all of the patients, this is all comers HPV-positive patients. So some of the patients are cervical patients, some head and neck, some anal or vaginal. And so the first phase, which was the monotherapy, the 2 dose was -- contained all comers. And to your point, the importance was that, first of all, they received multiple doses of this vaccine and some of them continue to receiving it as we are talking. And secondly, the first 3 patients, of course, that we -- as a preliminary, we test that. What they -- was showed that, upon injection, every dose that was given, now you have the higher or I should say, more trained T cells that can see the tumor and kill that. So you are, in a way, increasing your army continuously to number of epitopes. And that's why I sort of said the analogy of TCR. Instead of manufacturing 5, 6, 7 different TCRs and then sending it for a specific antigen, this virus actually does that directly internally. And to the point that you raised as far as if we anticipate, that is our anticipation that actually by educating the T cell, expanding them directly in patients, they will combat the tumor, and you will see clinical activities. And especially when you combine it, I think, it will be very exciting. And right now, as we speak, they are treating patients in a combination at NCI.

Okay. Okay. And then I guess, where are you administering the vaccine? Is it sort of local or intratumoral injection? Or is this a systemic delivery?

It's subcutaneous, actually. It's very simple. And it's subcutaneous. And these vaccines are just basically given subcutaneously to the patient. Very little discomfort. You get basically the same kind of discomfort that when you get flu shots.

Sure. Okay. Okay. All right. Maybe just coming back to the UltraCAR-T programs, the ovarian cancer program. I guess data, so far, have been in subjects that have been administered the product intraperitoneally. And next steps would be to move towards an IV, I believe, application. I suppose would we -- as we kind of look to kind of further updates over the course of '21, would you -- I guess, when will you be in a position to evaluate IV administration? Or is that sort of data dependent? Would you like, ultimately, kind of move forward to an IV administration with this program?

Excellent question. We will move toward the IV. Originally when the trial was designed, and because, again, this is a first in a mankind, there was no precedence for this kind of platform. FDA asked us to do 1 arm first intraperitoneally and get the safety as well as the dose, and then move to the second arm, which is the IV, intravenously. We will be doing that also in conjunction that FDA has asked us. Once we establish the dose with the IP, we can now go back and redose. Which we will be doing that as well, which is quite important, especially for this platform, which allows that at a very low-cost and very little effort to be very honest. And as far as -- one other aspect that we will also introduce here, these trials are done without any lymphodepletion. We will also interrogate the effect of lymphodepletion. But we are very excited to move the IP arm very rapidly to higher doses and then to the expansion phase because that's where you can actually look at the efficiency and effectiveness as you have more -- 30 to 50 patients. And this is one of the things we are anticipating and moving forward with some of the really excellent centers in the world that they are coming on board with us. They are very excited about this and also in IV similarly. So we will be reporting interim data on all of that in 2020.

Okay. All right. Maybe -- yes. I guess from the preclinical work, would you expect to see a difference in CAR-T expansion delivered IV versus intraperitoneally, would there be difference there? Or is it sort of more potentially conditioning lymphodepletion that sort of might potentiate greater cell expansion?

Excellent questions there. That we do -- actually, I believe that there would be differences because when intraperitoneally, some of these patients, for instance, they do have lesions intraperitoneally. And then when we are following, and even in preliminary data that we showed, the UltraCAR in the blood, blood doesn't have that much of the antigen, as you can imagine, in the solid tumors, which is completely opposite what is in hematological one. And in R&D, we actually showed that. When you look at the AML patient, for instance, and you follow the expansion and persistence there, it's a very, very clean pictures that you see. Because majority of the blasts are in the blood, if you have ALL or multiple myeloma, any of them. And you can see that as they see the antigen, they expand and then eventually they just flat and then persist as they clean up the blast cells. So that's why I think it's very important for us to see the IV injection, which now allows to go more to the site. Of course, we might not be able to follow them directly intravenously, but then we can follow the effect on various lesions in different organs. And I think that will be a very important data as well. And at some point, there might be a solution that if the patients have both lesions intraperitoneally and other distant organs, then it might be also the possibility that you give doses in both sites. It's not -- basically you're not restricted just to put it intraperitoneally or IV, you can do 1 dose IV and 1 dose also IP.

Yes, makes a lot of sense. Okay. All right. Well, great. I think we'll have to leave it there for time. But thanks again, Helen, for sharing some of your time with us this afternoon. Thank you for tuning into the webcast.

Thank you for having me. I really appreciate it.